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Sample records for leukocytes neutrophils lymphocytes

  1. Indium-111 labeling of leukocytes: a detrimental effect on neutrophil and lymphocyte function and an improved method of cell labelling

    International Nuclear Information System (INIS)

    Segal, A.W.; Deteix, P.; Garcia, R.; Tooth, P.; Zanelli, G.D.; Allison, A.C.

    1978-01-01

    A technique for the labeling of cells with the gamma emitter indium-111 has recently been developed. In this study the effects of the labeling procedure on some in vitro functions of human neutrophils and lymphocytes were investigated. With the standard labeling procedure, neutrophil chemotaxis was reduced to approximately 50% of normal and lymphocytes lost surface receptors and failed to respond to stimulation with phytohemagglutinin. The 8-hydroxyquinoline that is used to chelate the indium is toxic to lymphocytes; accordingly the relationship between the quantity of oxine, the chelation of indium, and cell labeling were investigated. Optimal conditions for In-111 cell labeling were established: 100 million cells in 10 ml Hanks' balanced salt solution are mixed with 5 μg of oxine in a mixture of 50 μl of ethanol and 200 μl of saline; they are incubated at 37 0 C for 10 min and then washed. Initially, neutrophils and lymphocytes appear functionally normal, but after 24 to 48 hr lymphocyte function is impaired as a result of radiation damage. This toxicity may limit studies by external scanning on the distribution and kinetics of lymphocytes labeled with In-111

  2. The effect of gamma ray on total leukocytes, lymphocytes and neutrophils on blood samples of smokers compared to non-smoker donors

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    Baydaa Taher Sih

    2017-01-01

    Conclusions: By increases the doses of γ-ray, the declining in the values of WBCs, lymphocytes, and neutrophils in the smokers blood is greater than of nonsmokers and this confirms that these cells are more fragile, weak, and less tolerant to external stimuli.

  3. Neutrophil Leukocyte: Combustive Microbicidal Action and Chemiluminescence

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    Robert C. Allen

    2015-01-01

    Full Text Available Neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple, potent, and focused. Neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen (O2 facilitating combustion. The spin conservation rules define the symmetry barrier that prevents direct reaction of diradical O2 with nonradical molecules, explaining why combustion is not spontaneous. In burning, the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical O2 to yield oxygenated radical products that further participate in reactive propagation. Neutrophil mediated combustion is by a different pathway. Changing the spin quantum state of O2 removes the symmetry restriction to reaction. Electronically excited singlet molecular oxygen (O2*1 is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe. The resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission, that is, chemiluminescence. This overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic-fermionic frontier orbital considerations. The necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism.

  4. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... between preoperatively measured neutrophil-lymphocyte ratio (NLR) – as an inflammation ... analgesic (tenoxicam – as the first drug of choice, paracetamol, tramadol, or pethidine) usage ... fracture fixation). Age, sex, type of ...

  5. Cytoplasmic lipid bodies of human neutrophilic leukocytes

    International Nuclear Information System (INIS)

    Weller, P.F.; Ackerman, S.J.; Nicholson-Weller, A.; Dvorak, A.M.

    1989-01-01

    The morphology and function of cytoplasmic lipid bodies in human neutrophils were evaluated. By transmission electron microscopy, neutrophil lipid bodies were cytoplasmic inclusions, usually several microns in diameter, that occasionally coalesced to attain a diameter up to 7 microM. Neutrophil lipid bodies were not enveloped by membrane but were often surrounded by a more electron-dense shell at their periphery. Normal peripheral blood neutrophils contained an average of approximately one lipid body per cell. Lipid bodies appeared in greater numbers in neutrophils from inflammatory lesions. Perturbation of neutrophils during conventional methods of cell isolation and purification modestly increased lipid body numbers in neutrophils, whereas incubation of neutrophils with 1 microM oleic acid rapidly induced lipid body formation over 30 to 60 minutes. After granulocytes were incubated for 2 hours with 3H-fatty acids, including arachidonic, oleic, and palmitic acids, electron microscopic autoradiography demonstrated that lipid bodies represented the predominant intracellular sites of localization of each of the three 3H-fatty acids. There was lesser labeling noted in the perinuclear cisterna, but not in cell membranes. Virtually all of each of the three 3H-fatty acids incorporated by the neutrophils were esterified into chromatographically resolved classes of neutral lipids or phospholipids. These findings indicate that cytoplasmic lipid bodies are more prominent in neutrophils in vivo engaged in inflammatory responses and that these organelles in human neutrophils function as sites of deposition of esterified, incorporated fatty acids

  6. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: are they useful for predicting gestational diabetes mellitus during pregnancy?

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    Sargın MA

    2016-04-01

    Full Text Available Mehmet Akif Sargın, Murat Yassa, Bilge Dogan Taymur, Ayhan Celik, Emrah Ergun, Niyazi Tug Department of Obstetrics and Gynecology, Fatih Sultan Mehmet Research and Training Hospital, Istanbul, Turkey Objective: We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR could be utilized to screen for gestational diabetes mellitus (GDM.Subjects and methods: NLR and PLR were assessed by retrospective analysis of 762 healthy and pregnant women with GDM. The patients were stratified into four groups, as follows: GDM (n=144, impaired glucose tolerance (n=76, only screen positive (n=238, and control (n=304.Results: The leukocyte, neutrophil, and lymphocyte counts were significantly higher in the study groups compared with the control group (P=0.001; P<0.01. There were no statistically significant differences between the groups with respect to the NLR and PLR (P>0.05.Conclusion: We do not recommend that blood NLR and PLR can be used to screen for GDM. However, increase in the leukocyte count is an important marker for GDM as it provides evidence of subclinical inflammation. Keywords: inflammation, lymphocytes, neutrophils, platelets, pregnancy

  7. Leukocyte counts and lymphocyte subsets in relation to pregnancy and HIV infection in Malawian women.

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    Mandala, Wilson L; Gondwe, Esther N; Molyneux, Malcolm E; MacLennan, Jenny M; MacLennan, Calman A

    2017-09-01

    We investigated leukocyte and lymphocyte subsets in HIV-infected or HIV-uninfected, pregnant or non-pregnant Malawian women to explore whether HIV infection and pregnancy may act synergistically to impair cellular immunity. We recruited 54 pregnant and 48 non-pregnant HIV-uninfected women and 24 pregnant and 20 non-pregnant HIV-infected Malawian women. We compared peripheral blood leukocyte and lymphocyte subsets between women in the four groups. Parturient HIV-infected and HIV-uninfected women had more neutrophils (each PHIV-uninfected parturient women had fewer CD4 + and γδ T cells, B and NK cells (each Ppregnancy. Malawian women at parturition have an increased total white cell count due to neutrophilia and an HIV-unrelated pan-lymphopenia. © 2017 The Author. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.

  8. Platelet indices and neutrophil to lymphocyte ratio in adults with ...

    African Journals Online (AJOL)

    Background: A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. Methods: Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with ...

  9. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    Background and Aim: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil‑lymphocyte ratio (NLR) – as an ...

  10. Mean platelet volume, neutrophil to lyphocyte ratio and platelet to lymphocyte ratio in psoriasis

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    Mehmet Ünal

    2015-06-01

    Full Text Available Background and Design: It has been demonstrated that ratio of neutrophil and platelet count systemic inflammation and is associated with prognosis of many cardiovascular diseases, malignates and chronic inflammatory diseases.As far as it is known, there are no studies investigating neutrophil/lymphocyeratio(NLR, platelet/lymphocyte ratio(PLR and mean platelet volume(MPV values together within the context of psoriasis, a chronic and systemic inflammatory disease. Materials and Methods: 320 patients followed up in our polyclinic with psoriasis vulgaris and 200 healthy persons were evaluated in the study. Results: Leukocyte, neutrophil, platelet, MPV, NLR and PLR values in patients with psoriasis were significantly higher, and lymphocyte count, on the other hand, was significantly lower than those of the control group. No significant difference was found between MPV, NLR and PLR values of patients with or without a family history, nail and joint involvement. Conclusions: These parameters may be made use of as cheap and easily applicable methods in predicting which psoriasis patients are under the risk of cardiovascular disease. PLR is a better inflammation marker than MPV and NLR in patients with psoriasis. We did not observe a significant relationship between MPV, NLR and PLR values and such disease characteristics as severity of disease, joint involvement, nail involvement and duration of disease in patients with psoriasis. So, we believe that there is little information on the extent to which MPV,NLR and PLR might be useful regarding these characteristics.

  11. Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids.

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    Gaelle Hirsch

    Full Text Available Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out.We assessed glucocorticoid-responsiveness in equine and human peripheral blood neutrophils and neutrophil-depleted leukocytes.Blood neutrophils and neutrophil-depleted leukocytes were isolated from 6 healthy horses and 4 human healthy subjects. Cells were incubated for 5 h with or without LPS (100 ng/mL alone or combined with hydrocortisone, prednisolone or dexamethasone (10(-8 M and 10(-6 M. IL-1β, TNF-α, IL-8, glutamine synthetase and GR-α mRNA expression was quantified by qPCR. Equine neutrophils were also incubated for 20 h with or without the three glucocorticoids and cell survival was assessed by flow cytometry and light microscopy on cytospin preparations.We found that glucocorticoids down-regulated LPS-induced pro-inflammatory mRNA expression in both cell populations and species. These drugs also significantly increased glutamine synthetase gene expression in both equine cell populations. The magnitude of glucocorticoid response between cell populations was generally similar in both species. We also showed that dexamethasone had a comparable inhibitory effect on pro-inflammatory gene expression in both human and equine neutrophils. As reported in other species, glucocorticoids significantly increase the survival in equine neutrophils.Glucocorticoids exert genomic effects of similar magnitude on neutrophils and on other blood leukocytes. We speculate that the poor response to glucocorticoids observed in some

  12. Neutrophils Are Not Less Sensitive Than Other Blood Leukocytes to the Genomic Effects of Glucocorticoids

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    Hirsch, Gaelle; Lavoie-Lamoureux, Anouk; Beauchamp, Guy; Lavoie, Jean-Pierre

    2012-01-01

    Background Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out. Objective We assessed glucocorticoid-responsiveness in equine and human peripheral blood neutrophils and neutrophil-depleted leukocytes. Methods Blood neutrophils and neutrophil-depleted leukocytes were isolated from 6 healthy horses and 4 human healthy subjects. Cells were incubated for 5 h with or without LPS (100 ng/mL) alone or combined with hydrocortisone, prednisolone or dexamethasone (10−8 M and 10−6 M). IL-1β, TNF-α, IL-8, glutamine synthetase and GR-α mRNA expression was quantified by qPCR. Equine neutrophils were also incubated for 20 h with or without the three glucocorticoids and cell survival was assessed by flow cytometry and light microscopy on cytospin preparations. Results We found that glucocorticoids down-regulated LPS-induced pro-inflammatory mRNA expression in both cell populations and species. These drugs also significantly increased glutamine synthetase gene expression in both equine cell populations. The magnitude of glucocorticoid response between cell populations was generally similar in both species. We also showed that dexamethasone had a comparable inhibitory effect on pro-inflammatory gene expression in both human and equine neutrophils. As reported in other species, glucocorticoids significantly increase the survival in equine neutrophils. Conclusions Glucocorticoids exert genomic effects of similar magnitude on neutrophils and on other blood leukocytes. We speculate that the poor response to

  13. Elevated Neutrophil Lymphocyte Ratio in Recurrent Optic Neuritis

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    Hande Guclu

    2015-01-01

    Full Text Available Purpose. To demonstrate the relation between optic neuritis (ON and systemic inflammation markers as neutrophil lymphocyte ratio (N/L ratio, platelet count, mean platelet volume (MPV, and red cell distribution width (RDW and furthermore to evaluate the utilization of these markers to predict the frequency of the ON episodes. Methods. Forty-two patients with acute ON and forty healthy subjects were enrolled into the study. The medical records were reviewed for age, sex, hemoglobin (Hb, Haematocrit (Htc, RDW, platelet count, MPV, white blood cell count (WBC, neutrophil and lymphocyte count, and neutrophil lymphocyte ratio (N/L ratio. Results. The mean N/L ratio, platelet counts, and RDW were significantly higher in ON group (p=0.000, p=0.048, and p=0.002. There was a significant relation between N/L ratio and number of episodes (r=0.492, p=0.001. There was a statistically significant difference for MPV between one episode group and recurrent ON group (p=0.035. Conclusions. Simple and inexpensive laboratory methods could help us show systemic inflammation and monitor ON patients. Higher N/L ratio can be a useful marker for predicting recurrent attacks.

  14. Association between neutrophil/lymphocyte ratio and coronary collateral circulation

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    Mustafa Oylumlu

    2012-03-01

    Full Text Available Objectives: To investigate relation between neutrophil/lymphocyte ratio and coronary collateral flow.Material and methods: Eighty-two patients admittedDicle University Medical Faculty Hospital Cardiology Departmentwith diagnosis of coronary artery disease anddetected significant stenosis or occlusion at least one ofthe coronary arteries, were included to study. Age, sex,presence of diabetes mellitus and hypertension, acute/stable coronary disease, body mass index, neutrophil/lymphocyte ratio, white blood count, Rentrop scores andnumber of diseased vessel were recorded.Results: Well-developed coronary collateral circulationwas found in 33 of the patients. Forty-nine patients hadpoor coronary collateral circulation. Mean age, sex, bodymass index, presence of diabetes mellitus and hypertensionwere similar in two groups. Mean neutrophil/lymphocyteratio was lower in well-developed coronary collateralcirculation group than poor coronary collateral circulationgroup, but there was no significant differences (2.78 vs2.89, p=0.12.Conclusions: There was no association between neutron/hil lymphocyte ratio and coronary collateral circulationaccording to our data. J Clin Exp Invest 2012; 3(1:29-32

  15. Correlation of Leukocyte Count and Percentage of Segmented Neutrophils with Pathohistological Findings of Appendix in Children

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    Marko Baskovic

    2018-01-01

    Full Text Available BackgroundAppendicitis is the most common indication for an emergency operation in children's age. Although none of the laboratory values has not high sensitivity and specificity for the diagnosis of appendicitis, leukocyte count and the percentage of segmented neutrophils are most commonly used. The aim of this study was to determine whether there is a statistically significant correlation between leukocyte count and the percentage of segmented neutrophils compared to the pathohistological finding of appendix in children. Materials and MethodsWe retrospectively analyzed the data in the period from 1 January 2016 to 31 December 2016. The analysis was made on 211 patients. Spearman's correlation coefficient (rs was calculated. We determined the specificity and sensitivity of leukocyte count and the percentage of segmented neutrophils used in the calculation of Alvorado and Pediatric Appendicitis score.ResultsThe results of the research have shown that the correlation between leukocyte count and the pathohistological findings is weak (rs = 0.29, p = 3.61*10-8, while there is no correlation between the percentage of segmented neutrophils and pathohistological findings (rs = 0.18, p = 7.08 *10-5. The sensitivity of leukocyte count is 93% and the specificity is 30%, while the sensitivity to the percentage of segmented neutrophils is 71% and the specificity is 50%. ROC analysis for leukocytes shows area under the curve of 0.648, while for segmented neutrophils of 0.574.ConclusionGiven the correlation results obtained, the clinical experience of physicians will still have one of the leading roles in diagnosing acute appendicitis in children.

  16. Effect of Weightlessness on Neutrophils and Lymphocytes of Rats

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    Khusi Muhammad Saqib, Zia-ur-Rahman1 and Saeed Ahmad Nagra2

    2012-01-01

    Full Text Available In the present study, two hundreds and forty healthy albino young (n=120 and old (n=120 rats were used during winter and summer season. Rats were divided into four groups in each season i.e. young and old, consisting of male (n=30 and female (n=30 in each age category. In each age  sex matched rats, three subgroups were made and have been given the name as cage control (CC group, horizontal restrained group (HR and head down suspended (HDS group. For winter season, the room temperature of experimental period ranged from 20 to 23°C and for summer season, the experimental room temperature ranged from 30 to 33°C. A 12 hours light/12 hours dark cycle with ad libitum food offered each day to an individual rats as well as fresh water (at normal temperature were provided every day from 9-10 h (morning Rats were decapitated on day 7th (n=5 and day 28th (n=5 of experimental period from all groups to collected the blood in a hepranized tubes for the estimation of lymphocytes and neutrophils. Appropriate statistical analysis was performed to estimate the difference between age, days, treatments and their possible interactions during each season. During winter and summer seasons, male and female rats did show a significant decrease in lymphocytes, however a significant increase in the neutrophils percent was also observed in the HR and HDS groups. During summer, a significant increase in neutrophils and a decrease in lymphocytes were observed in male and female rats of HR and HDS groups.

  17. Nebivolol Attenuates Neutrophil Lymphocyte Ratio: A Marker of Subclinical Inflammation in Hypertensive Patients

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    Mazhar Hussain

    2017-01-01

    Full Text Available Background. High value of neutrophil lymphocyte ratio (NLR is a strong independent predictor and biomarker of ongoing vascular inflammation in various cardiovascular disorders. Objective. The main focus of the study is to investigate the effect of nebivolol on NLR in mild to moderate hypertensive patients in comparison with metoprolol. In addition, BMI, blood pressure, TLC count, blood sugar, and lipid profile were also assayed before and after treatment. Materials and Methods. In this 12-week prospective double-blinded randomized study, 120 patients with mild to moderate hypertension were randomly divided into two groups to prescribed daily dose of tab nebivolol 5–10 mg and metoprolol 50–100 mg, respectively, for 12 weeks. The data were analyzed using SPSS 16 software. Results. A total of 100 patients completed the study. Both drugs lowered blood pressure significantly, nebivolol 20.5/10.5 and metoprolol 22.5/11.2 (p<0.001 from baseline. Regarding inflammation, nebivolol reduced total leukocyte count (p=0.005 and neutrophil count (p=0.003 and increased lymphocyte count (p=0.004 as compared to metoprolol. Similarly, nebivolol but not metoprolol significantly reduced NLR ratio (p=0.07. Nebivolol improved lipid profile and blood sugar compared to metoprolol, but values were nonsignificant. Conclusion. Nebivolol has a strong impact on reducing NLR, a marker of subclinical inflammation in hypertensive patients. Moreover NLR can be used as a disease and drug monitoring tool in these patients.

  18. Differences in leukocyte differentiation molecule abundances on domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) neutrophils identified by flow cytometry.

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    Highland, Margaret A; Schneider, David A; White, Stephen N; Madsen-Bouterse, Sally A; Knowles, Donald P; Davis, William C

    2016-06-01

    Although both domestic sheep (DS) and bighorn sheep (BHS) are affected by similar respiratory bacterial pathogens, experimental and field data indicate BHS are more susceptible to pneumonia. Cross-reactive monoclonal antibodies (mAbs) for use in flow cytometry (FC) are valuable reagents for interspecies comparative immune system analyses. This study describes cross-reactive mAbs that recognize leukocyte differentiation molecules (LDMs) and major histocompatibility complex antigens on DS and BHS leukocytes. Characterization of multichannel eosinophil autofluorescence in this study permitted cell-type specific gating of granulocytes for evaluating LDMs, specifically on neutrophils, by single-label FC. Evaluation of relative abundances of LDMs by flow cytometry revealed greater CD11a, CD11b, CD18 (β2 integrins) and CD 172a (SIRPα) on DS neutrophils and greater CD14 (lipopolysaccharide receptor) on BHS neutrophils. Greater CD25 (IL-2) was identified on BHS lymphocytes following Concavalin A stimulation. While DS and BHS have similar total peripheral blood leukocyte counts, BHS have proportionately more neutrophils. Published by Elsevier Ltd.

  19. Preoperative neutrophil response as a predictive marker of clinical outcome following open heart surgery and the impact of leukocyte filtration.

    LENUS (Irish Health Repository)

    Soo, Alan W

    2010-11-01

    Open heart surgery is associated with a massive systemic inflammatory response. Neutrophils, are the main mediator of this response. We hypothesised that the degree of neutrophil activation and inflammatory response to open heart surgery varies individually and correlates with clinical outcome. The aim of this study was to determine if individual clinical outcome can be predicted preoperatively through assessment of in-vitro stimulated neutrophil responses. Following that, the effects of neutrophil depletion through leukocyte filters are examined.

  20. The neutrophil to lymphocyte ratio in patients supported with extracorporeal membrane oxygenation.

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    Yost, Gardner; Bhat, Geetha; Pappas, Patroklos; Tatooles, Antone

    2018-04-01

    The neutrophil to lymphocyte ratio (NLR) has proven to be a robust predictor of mortality in a wide range of cardiovascular diseases. This study investigated the predictive value of the NLR in patients supported by extracorporeal membrane oxygenation (ECMO) systems. This study included 107 patients who underwent ECMO implantation for cardiogenic shock. Median preoperative NLR was used to divide the cohort, with Group 1 NLR <14.2 and Group 2 with NLR ≥14.2. Survival, the primary outcome, was compared between groups. The study cohort was composed of 64 (60%) males with an average age 53.1 ± 14.9 years. Patients in Group 1 had an average NLR of 7.5 ± 3.5 compared to 27.1 ± 19.9 in Group 2. Additionally, those in Group 2 had significantly higher preoperative blood urea nitrogen (BUN) and age. Survival analysis indicated a thirty-day survival of 56.2%, with significantly worsened mortality in patients with NLR greater than 14.2, p=0.047. Our study shows the NLR has prognostic value in patients undergoing ECMO implantation. Leukocytes are known contributors to myocardial damage and neutrophil infiltration is associated with damage caused by myocardial ischemia.

  1. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    International Nuclear Information System (INIS)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-01-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

  2. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

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    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-11-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

  3. Evaluation of the relationship between fungal infection, neutrophil leukocytes and macrophages in cervicovaginal smears: Light microscopic examination

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    Sayeste Demirezen

    2015-01-01

    Conclusions: Our findings indicate that macrophages and neutrophils may play a determining role in host defense against fungal infection together, but neither yeast nor filamentous forms affect the presence of neutrophil leukocytes and macrophages. As a result of this, both yeast and filamentous forms may have pathogenic effects.

  4. 2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio

    NARCIS (Netherlands)

    Lin, Bochao Danae; Carnero-Montoro, Elena; Bell, Jordana T; Boomsma, Dorret I; de Geus, Eco J; Jansen, Rick; Kluft, Cornelis; Mangino, Massimo; Penninx, Brenda; Spector, Tim D; Willemsen, Gonneke; Hottenga, Jouke-Jan

    2017-01-01

    Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and

  5. Radiolabeled leukocytes

    International Nuclear Information System (INIS)

    Datz, F.L.; Taylor, A.T.

    1986-01-01

    Leukocytes are a heterogeneous group of nucleated cells that follow similar patterns of differentiation in the bone marrow. Although the various leukocyte cell types perform somewhat different functions, they act as a group to protect the host from hazards of the internal and external environment, such as infection and neoplasia, and they assist in the repair of damaged tissue. Leukocytes spend a small fraction of their life in the peripheral blood, using it only for transportation to sites where they are needed to perform their defensive functions. In adults, the mature types of leukocytes are neutrophils (59 percent of the leukocyte population), lymphocytes (34 percent), monocytes (four percent), eosinophils (three percent), and basophils (0.5 percent). Neutrophils, eosinophils, and basophils all contain nuclei with finitely granular, evenly distributed chromatin and are collectively called granulocytes. In addition to the main categories of leukocytes listed above, there are subsets of many of these classes of cells; for example, natural killer cells are a subset of lymphocytes

  6. Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis.

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    Yin, Yongmei; Wang, Jun; Wang, Xuedong; Gu, Lan; Pei, Hao; Kuai, Shougang; Zhang, Yingying; Shang, Zhongbo

    2015-07-01

    Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; P(heterogeneity)=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; P(heterogeneity)=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; P(heterogeneity)=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; P(heterogeneity)=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer.

  7. Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract cancers: a systematic review and meta-analysis.

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    Tang, Haowen; Lu, Wenping; Li, Bingmin; Li, Chonghui; Xu, Yinzhe; Dong, Jiahong

    2017-05-30

    Inflammation was considered to perform crucial roles in the development and metastasis of malignancies. A heightened neutrophil-lymphocyte ratio has been described to be associated with detrimental survivals in different malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte ratio on survivals in biliary tract cancer. The review evaluated the prognostic value of neutrophil-lymphocyte ratio in biliary tract cancer. MEDLINE, the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically searched for relevant articles. Associations between neutrophil-lymphocyte ratio and long-term outcomes were expressed as the hazard ratios and 95% confidence intervals. The odds ratio was utilized to assess the association between neutrophil-lymphocyte ratio and clinicopathological parameters. Fourteen studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened pretreatment neutrophil-lymphocyte ratio was significantly associated with detrimental overall survival and relapse free survival for biliary tract cancer patients. In addition, elevated neutrophil-lymphocyte ratio was positively correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and greater lymph node involvement. This meta-analysis marked that an increased pretreatment neutrophil-lymphocyte ratio was significantly linked with detrimental long-term outcomes and clinicopathological parameters for patients with biliary tract cancer.

  8. Assessment of neutrophil / lymphocyte ratio in patients with myocardial bridge

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    Abdulkadir Yıldız

    2014-03-01

    Full Text Available Objective: Myocardial bridge (MB is a congenital anomaly characterized by systolic narrowing of the epicardial coronary arterial segment while traveling in the myocardium. It is a benign entity but previous studies showed that the proximal portion is prone to an enhanced atherosclerosis. Neutrophil/lymphocyte ratio (NLR is a sensitive marker of systemic inflammation used as a predictor for adverse cardiovascular outcomes in atherosclerotic heart disease. So in this study, we sought to evaluate the association between NLR and myocardial bridging. Methods: A total of 172 patients (mean age: 50.8 ± 11.5 years, 77.3% men with either angiographically proven MB or normal coronary arteries were included in the study. For the entire study population, hematologic parameters were measured using an automatic blood counter. Results: The study population consisted of 71 patients with MB (mean age: 51.4 ± 11.9 years, 80.3% male and 101 patients with normal coronary arteries (mean age: 50.5 ± 11.3 years, 75.2% male. There were no significant differences between groups regarding hemoglobin level, platelet count, glucose and creatinine. Compared to the control group, NLR was significantly higher in patients with MB (2.45 ± 1.19 vs. 1.72 ± 0.48; p 1.82 predicted myocardial bridge presence with 70% sensitivity and 71% specificity (ROC area under curve: 0.733, 95% CI: 0.654-0.811, p < 0.001. Conclusion: Our study findings demonstrated that MB is associated with elevated NLR, which is used to assess inflammatory status of the body. J Clin Exp Invest 2014; 5 (1: 24-28

  9. Associations between lifestyles and neutrophil-lymphocyte and platelet-lymphocyte ratios in colorectal cancer.

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    Hong, Chuyuan; Wei, Yisheng; Jiang, Jianxin; Zhao, Chuxiong; Liang, Guojian; Wang, Guoqiang; Yang, Hui

    2014-06-01

    To explore the etiology of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) abnormalities in colorectal cancer. In total, 230 patients with histopathologically confirmed colorectal cancer from August 2009 to August 2011 were recruited to our study. The associations between lifestyles (smoking, alcohol and pickled food consumption) and pretreatment NLR and PLR were estimated using the Kruskal-Wallis tests and linear regression model. The Kruskal-Wallis test showed a significant association between pickled food intake and pretreatment NLR but not PLR (P = 0.002, 0.057, respectively). Pairwise comparisons showed that, compared with those with a moderately frequent (2-3 times/week) and an infrequent (≤ once a week) intake of pickled food, high frequency (≥ four times/week) consumption of pickled food had a higher pretreatment NLR (P = 0.01, 0.007, respectively). Multivariate linear regression analysis showed pretreatment NLR increased significantly in high frequency (≥ four times/week) consumption of pickled food (P frequency intake of pickled food possibly contributes to higher NLR, which may reflect a systemic inflammatory response in colorectal cancer. © 2013 Wiley Publishing Asia Pty Ltd.

  10. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

    Science.gov (United States)

    Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

    2018-06-08

    The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Investigation of neutrophil-to-lymphocyte ratio and mean platelet volume in sudden hearing loss,

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    Rauf Oguzhan Kum

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Several theories attempt to explain the pathophysiology of sudden hearing loss. OBJECTIVE: The objective of this study was to investigate the possible role of inflammation and atherothrombosis in sudden hearing loss patients through the neutrophil-to-lymphocyte ratio and mean platelet volume. METHODS: Study design - retrospective cross-sectional historical cohort. This study was conducted on two groups: one with 59 individuals diagnosed with sudden hearing loss, and other with 59 healthy individuals with the same characteristics of gender and age distribution, neutrophil-to-lymphocyte ratio and mean platelet volume levels were measured in patients diagnosed with sudden hearing loss as well as in the control group, and it was verified whether these results interfered for a better or worse prognosis with treatment of sudden deafness. RESULTS: Neutrophil-to-lymphocyte ratio levels are much higher in patients diagnosed with sudden hearing loss compared to the control group. Similarly, mean levels of neutrophil-to-lymphocyte ratio are higher in non-recovered versus recovered patients (p = 0.001. However, we could not find a correlation with mean platelet volume levels (p > 0.05. CONCLUSION: Neutrophil-to-lymphocyte ratio is a quick and reliable indicator regarding diagnosis and prognosis of sudden hearing loss; on the other hand, mean platelet volume may be considered a less important indicator in this aspect.

  12. Effect of serial-day exposure to nitrogen dioxide on airway and blood leukocytes and lymphocyte subsets

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, C.; Chen, L.L.; Erle, D.J.; Balmes, J.R. [Univ. of California, Lung Biology Center and Center for Occupational and Environmental Health, San Francisco, CA (United States); Christian, D.L.; Welch, B.S.; Dunham, E. [Univ. of California, Lung Biology Center, San Francisco, CA (United States); Kleinman, M.T. [Univ. of California, Dept. of Community and Environmental Medicine, Irvine, CA (United States)

    2000-07-01

    Nitrogen dioxide (NO{sub 2}) is a free radical-producing oxidant gas. Inhalation of NO2 could cause airway inflammation, and decrease immune function. This experiment tested the hypothesis that exposure to NO{sub 2} would: (1) increase leukocytes in bronchoalveolar lavage (BAL); and (2) change the distribution of lymphocyte subsets and activation in BAL and peripheral blood (PB). Using a counter-balanced, repeated-measures design, 15 healthy volunteers were exposed to filtered air (FA) or 2.0 parts per million NO{sub 2} for 4 h.day{sup -1} (4 x 30 min of exercise), for three consecutive days. Bronchoscopy was performed 18 h following each exposure set, and PB was drawn pre-exposure and pre-bronchoscopy. Flow cytometry was used to enumerate lymphocyte subsets and activation makers in BAL and PB. In the bronchial fraction, there was an increase in the percentage of neutrophils following NO2 exposure compared to FA (median (interquartile range): 10.6 (4.8. 17.2)% versus 5.3 (2.5-8.3)%; p=0.005). In the BAL, there was a decrease in the percentage of T-helper cells following NO{sub 2} exposure compared to FA (55.9 (40.8-62.7)% versus 61.6 (52.6-65.2)%; p=0.022). For PB, there were no between-condition differences in any leukocyte or lymphocyte subsets, or activation. In conclusion exposure to nitrogen dioxide results in bronchial inflammation and a minimal change in bronchoalveolar lavage T-helper cells, and no changes in peripheral blood cells. (au)

  13. The neutrophil-to-lymphocyte ratio as a marker of systemic endothelial dysfunction in asymptomatic subjects.

    Science.gov (United States)

    Martínez-Urbistondo, Diego; Beltrán, Almudena; Beloqui, Oscar; Huerta, Ana

    2016-01-01

    The neutrophil-to-lymphocyte ratio has demonstrated to be a prognostic inflammatory marker in cardiovascular disease. The objective of this study is to evaluate the association between neutrophil-to-lymphocyte ratio and pathologic urinary albumin/creatinine ratio as an early marker of cardiovascular risk and systemic endothelial dysfunction, associated with microvascular disease, in asymptomatic subjects. A unicenter cross-sectional study was conducted, including 1816 asymptomatic subjects. Patients with previous cardiovascular disease, those who were treated with ACE inhibitors and/or angiotensin II receptor blockers and patients with albumin/creatinine ratio over 300mg/g were excluded. The outcome of the study was the presence of a pathologic urinary albumin/creatinine ratio. The neutrophil-to-lymphocyte ratio was significantly associated with altered urinary albumin/creatinine ratio in the univariate analysis and after adjustment for other known endothelial and cardiovascular risk factors (age, hypertension, dyslipidaemia, diabetes or altered glomerular filtration rate). Based on the sensitivity and specificity of different neutrophil-to-lymphocyte ratio thresholds, 3 risk groups were created for altered urinary albumin/creatinine ratio: low risk in those with neutrophil-to-lymphocyte ratio 3. These groups were found to have a statistically significant and independent prognostic power for altered urinary albumin/creatinine ratio in asymptomatic patients. The neutrophil-to-lymphocyte ratio appears to be a cost-efficient, non-invasive and independent potential marker of systemic endothelial dysfunction in asymptomatic subjects. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

    2013-07-15

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K{sub M} 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V{sub max}. PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion

  15. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    International Nuclear Information System (INIS)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François

    2013-01-01

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K M 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V max . PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion trapping

  16. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Wang D

    2013-03-01

    Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

  17. A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

    Science.gov (United States)

    Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

    2017-10-01

    To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

  18. Elevated neutrophil-lymphocyte ratio in patients with euthyroid chronic autoimmune thyreotidis

    Directory of Open Access Journals (Sweden)

    Keskin Havva

    2016-07-01

    Full Text Available Objective. The neutrophil-lymphocyte ratio (NLR, determined from peripheral blood, is accepted as an available and practical indicator of the systemic inflammation. In this study, we aimed to determine whether the NLR was higher in euthyroid chronic autoimmune thyreotidis (CAT patients compared to a healthy control group.

  19. Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sørensen, Allan Klitgaard; Holmgaard, Dennis Back; Mygind, Lone Hagens

    2015-01-01

    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and progressive decline in pulmonary function. Neutrophil-to-lymphocyte ratio (NLR), YKL-40 and calprotectin are biomarkers of inflammation and predict mortality in patients with different inflammatory...... diseases. We aimed to investigate the correlation between levels of these three biomarkers and neutrophil granulocyte and lymphocyte count in patients with moderate to very severe COPD stratified by use of systemic glucocorticoids. Furthermore, we studied the ability of these biomarkers to predict all......- and multivariate Cox regression analyses with hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Plasma calprotectin was positively correlated with neutrophil granulocyte count and NLR. No significant association was found between plasma YKL-40 and the cellular biomarkers, irrespective...

  20. Neutrophil-to-lymphocyte ratio as an independent predictor for survival in patients with localized clear cell renal cell carcinoma after radiofrequency ablation: a propensity score matching analysis.

    Science.gov (United States)

    Chang, Xiaofeng; Zhang, Fan; Liu, Tieshi; Wang, Wei; Guo, Hongqian

    2017-06-01

    To investigate the role of neutrophil-to-lymphocyte ratio as a prognostic indicator in patients with localized clear cell renal cell carcinoma treated with radiofrequency ablation. We retrospectively analyzed data from patients with renal cell carcinoma who underwent radiofrequency ablation from 2006 to 2013. The Kaplan-Meier method was used to generate the survival curves according to different categories of neutrophil-to-lymphocyte ratio. Relationships between preoperative neutrophil-to-lymphocyte ratio or the change of neutrophil-to-lymphocyte ratio and survival were evaluated with multivariable Cox proportional hazards regression analysis. A propensity score matching analysis was carried out to avoid confounding bias. A total of 185 patients were included in present study. When stratified by preoperative neutrophil-to-lymphocyte ratio cutoff value of 2.79, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio analysis, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio ratio with the change of neutrophil-to-lymphocyte ratio, patients with both preoperative neutrophil-to-lymphocyte ratio ≥2.79 and the change of neutrophil-to-lymphocyte ratio ≥0.40 had the worst disease-free survival. Results of multivariable analysis showed that preoperative neutrophil-to-lymphocyte ratio and the change of neutrophil-to-lymphocyte ratio correlated with cancer relapse remarkably. High preoperative neutrophil-to-lymphocyte ratio and elevated postoperative neutrophil-to-lymphocyte ratio are associated with significant increase in risk of local recurrence as well as distant metastasis. The combination of neutrophil-to-lymphocyte ratio with the other prognostic indicators can be applied in the evaluation of relapse risk in patients with clear cell renal cell carcinoma after radiofrequency ablation.

  1. Clinical Significance of the Neutrophil-to-Lymphocyte Ratio in Endocrine Therapy for Stage IV Breast Cancer.

    Science.gov (United States)

    Iimori, Nozomi; Kashiwagi, Shinichiro; Asano, Yuka; Goto, Wataru; Takada, Koji; Takahashi, Katsuyuki; Hatano, Takaharu; Takashima, Tsutomu; Tomita, Shuhei; Motomura, Hisashi; Hirakawa, Kosei; Ohira, Masaichi

    2018-01-01

    Studies have found that patients with cancer exhibit abnormal leukocyte fractions, such as elevated neutrophil count and diminished lymphocyte count, and that the neutrophil-to-lymphocyte ratio (NLR) provides a surrogate marker for prognosis and response to treatment of patients after radical surgery for several different types of cancer. However, few reports have addressed the association between the NLR and response to endocrine therapy. In this study, we carried out a clinical investigation to confirm whether or not the NLR predicted the response to endocrine therapy of stage IV breast cancer. The study subjects were 34 patients who underwent endocrine therapy as initial drug therapy for stage IV breast cancer. The correlation between NLR and prognosis, including the efficacy of endocrine therapy, was evaluated retrospectively. Among the 34 patients, the NLR was high in 10 (29.4%) and low in 24 (70.6%). In analysis of outcomes, the group with low NLR had a significant prolongation of progression-free survival (p=0.003), time to treatment failure (p=0.031), and overall survival (p=0.013) compared to the group with high NLR. Univariate analysis of progression-free survival found that responding to treatment [hazard ratio (HR)=4.310, p=0.004] and low NLR (HR=3.940, p=0.016) were factors associated with a favorable prognosis. Multivariate analysis also showed that responding to treatment (HR=4.329, p=0.006) and low NLR (HR=3.930, p=0.008) were independent factors associated with a favorable prognosis. Our results suggested that the NLR may represent a predictive marker for response to endocrine therapy in stage IV breast cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils.

    Science.gov (United States)

    Ohira, Taisuke; Bannenberg, Gerard; Arita, Makoto; Takahashi, Minoru; Ge, Qingyuan; Van Dyke, Thomas E; Stahl, Gregory L; Serhan, Charles N; Badwey, John A

    2004-08-01

    Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in several models of acute inflammation. In this study, we examined the effects of 15-epi-16-(p-fluoro)-phenoxy-lipoxin A(4) methyl ester, an aspirin-triggered lipoxin A(4)-stable analog (ATLa), on the protein phosphorylation pattern of human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by ATLa (10-50 nM). This 55-kDa protein was identified as leukocyte-specific protein 1, a downstream component of the p38-MAPK cascade in neutrophils, by mass spectrometry, Western blotting, and immunoprecipitation experiments. ATLa (50 nM) also reduced phosphorylation/activation of several components of the p38-MAPK pathway in these cells (MAPK kinase 3/MAPK kinase 6, p38-MAPK, MAPK-activated protein kinase-2). These results indicate that ATLa exerts its anti-inflammatory effects, at least in part, by blocking activation of the p38-MAPK cascade in neutrophils, which is known to promote chemotaxis and other proinflammatory responses by these cells.

  3. Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model

    OpenAIRE

    Chrom, Pawel; Stec, Rafal; Bodnar, Lubomir; Szczylik, Cezary

    2017-01-01

    Purpose The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy. Materials and Methods This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC m...

  4. A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review.

    Science.gov (United States)

    Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer

    2017-10-01

    Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have recently been used as indicators of inflammation. Higher MLR and PLR values have been determined in the euthymic and manic periods in patients with bipolar disorder compared to a control group. High NLR values were determined in the only study investigating this ratio in schizophrenia patients. The purpose of this study was to compare NLR, PLR and MLR values and complete blood count elements in patients receiving treatment and hospitalized due to schizophrenic psychotic episode and bipolar disorder manic episode. All patients meeting the inclusion criteria among subjects receiving treatment and hospitalized due to schizophrenia-psychotic episode and bipolar affective disorder-manic episode at the Ondokuz Mayıs University Medical Faculty Psychiatry Department, Turkey, in 2012-2016 were included in our study. A total of 157 healthy donors were included as a control group. White blood cell (WBC), neutrophil, lymphocyte, platelet and monocyte numbers were noted retrospectively from complete blood counts at time of admission, and NLR, PLR and MLR were calculated from these. NLR, PLR and MLR values and platelet numbers in this study were higher and lymphocyte numbers were lower in bipolar disorder patients compared to the controls. Elevation in NLR, MLR and PLR values and neutrophil numbers and lower lymphocyte numbers were determined in schizophrenia patients compared to the controls. Higher NLR and MLR values were found in schizophrenia patients compared to bipolar disorder. Findings of our study supported the inflammation hypothesis for schizophrenia and bipolar disorder.

  5. Association of High Density Lipoprotein with Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Coronary Artery Disease Patients

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    Jayesh H. Prajapati

    2014-01-01

    Full Text Available Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR and neutrophil-lymphocyte ratio (NLR with high density lipoprotein (HDL cholesterol levels in coronary artery disease (CAD patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P=0.008 and NLR (P=0.009; however no significant relationship was obtained with HDL and isolated platelet (P=0.488, neutrophil (P=0.407, and lymphocyte (P=0.952 counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P=0.024 and NLR (P=0.03 were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P=0.01 and NLR (6.33 versus 5.10; P=0.01 were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P=0.007 and NLR (P=0.001 were inversely associated with HDL, whereas in older population only NLR (P=0.05 had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.

  6. Predictive contribution of neutrophil/lymphocyte ratio in diagnosis of brucellosis.

    Science.gov (United States)

    Olt, Serdar; Ergenç, Hasan; Açıkgöz, Seyyid Bilal

    2015-01-01

    Here we wanted to investigate predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the diagnosis of brucellosis. Thirty-two brucellosis patients diagnosed with positive serum agglutination test and thirty-two randomized healthy subjects were enrolled in this study retrospectively. Result with ROC analyzes the baseline NLR and hemoglobin values were found to be significantly associated with brucellosis (P = 0.01, P = 0.01, resp.). Herein we demonstrated for the first time that NLR values were significantly associated with brucellosis. This situation can help clinicians during diagnosis of brucellosis.

  7. The Relationship Between 14C Urea Breath Test Results and Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios

    Directory of Open Access Journals (Sweden)

    Ertan Şahin

    2018-04-01

    Full Text Available Aim: Neutrophil/lymphocyte ratio (NLR and platelet/lymphocyte ratio (PLR are used as inflammatory markers in several diseases. However, there are little data regarding the diagnostic ability of NLR and PLR in Helicobacter pylori. We aimed to assess the association between the 14C urea breath test (14C-UBT results and NLR and PLR in H. pylori diagnosis. Methods: Results of 89 patients were retrospectively analysed in this study. According to the 14C-UBT results, patients were divided into two groups: H. pylori (+ and H. pylori (- (control group. Haematological parameters, including hemoglobine, white blood cell (WBC count, neutrophil count, lymphocyte count, NLR, platelet count, and PLR were compared between the two groups. Results: The mean total WBC count, neutrophil count, NLR and PLR in H. pylori (+ patients were significantly higher than in the control group (p<0.001 for all these parameters. In the receiver operating characteristic curve analysis, the cut-off value for NLR and PLR for the presence of H. pylori was calculated as ≥2.39 [sensitivity: 67.3%, specificity: 79.4%, area under the curve (AUC: 0.747 (0.637-0.856, p<0.0001] and ≥133.3 [sensitivity: 61.8%, specificity: 55.9%, AUC: 0.572 (0.447-0.697, p<0.05], respectively. Conclusion: The present study shows that NLR and PLR are associated with H. pylori positivity based on 14C-UBT, and they can be used as an additional biomarker for supporting the 14C-UBT results.

  8. Effects of Acer okamotoanum sap on the function of polymorphonuclear neutrophilic leukocytes in vitro and in vivo.

    Science.gov (United States)

    An, Beum-Soo; Kang, Ji-Houn; Yang, Hyun; Yang, Mhan-Pyo; Jeung, Eui-Bae

    2013-02-01

    Sap is a plant fluid that primarily consists of water and small amounts of mineral elements, sugars, hormones and other nutrients. Acer mono (A. mono) is an endemic Korean mono maple which was recently suggested to have health benefits due to its abundant calcium and magnesium ion content. In the present study, we examined the effects of sap from Acer okamotoanum (A. okamotoanum) on the phagocytic response of mouse neutrophils in vivo and rat and canine neutrophils in vitro. We tested the regulation of phagocytic activity, oxidative burst activity (OBA) and the levels of filamentous polymeric actin (F-actin) in the absence and presence of dexamethasone (DEX) in vitro and in vivo. Our results showed that DEX primarily reduced OBA in the mouse neutrophils, and that this was reversed in the presence of the sap. By contrast, the phagocytic activity of the mouse cells was not regulated by either DEX or the sap. Rat and canine polymorphonuclear neutrophilic leukocytes (PMNs) responded in vitro to the sap in a similar manner by increasing OBA. However, regulation of phagocytic activity by the sap was different between the species. In canine PMNs, phagocytic activity was enhanced by the sap at a high dose, while it did not significantly modulate this activity in rat PMNs. These findings suggest that the sap of A. okamotoanum stimulates neutrophil activity in the mouse, rat and canine by increasing OBA in vivo and in vitro, and thus may have a potential antimicrobial effect in the PMNs of patients with infections.

  9. [Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

    Science.gov (United States)

    Ruszczak, Z; Ciborska, L; Kaszuba, A

    1988-12-01

    The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

  10. Prediction of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma by Using Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio.

    Science.gov (United States)

    Ozgonul, Cem; Sertoglu, Erdim; Mumcuoglu, Tarkan; Ozge, Gokhan; Gokce, Gokcen

    2016-12-01

    To assess the levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with pseudoexfoliation syndrome (PEX) and to compare the NLR and PLR results of patients with PEX, PEX glaucoma (PXG), and healthy controls. In total, 34 patients with PEX, 29 patients with PXG, and 42 healthy subjects were enrolled in this retrospective study. Complete ophthalmologic examination and complete blood count measurements were performed of all subjects. Complete blood counts were performed within 2 h of blood collection. There was a significant difference in NLR between PEX and control groups (p = 0.012) and PXG and control groups (p = 0.003). Also, a significant difference was found in PLR values between control and PXG groups (p = 0.024). Our study for the first time provides evidence that PLR and NLR may be useful for predicting the prognosis of PEX patients and progression to PXG.

  11. Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy

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    Fatih Mehmet Yazar

    2015-11-01

    Full Text Available Acute appendicitis (AA is not uncommon during pregnancy but can be difficult to diagnose. This study evaluated the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR in addition to conventional diagnostic indicators of the disease to diagnose AA during pregnancy. Age, gestational age, white blood cell (WBC count, Alvarado scores, C-reactive protein (CRP, lymphocyte count, NLR and PLR were compared among 28 pregnant women who underwent surgery for AA, 35 pregnant women wrongly suspected as having AA, 29 healthy pregnant women, and 30 nonpregnant healthy women. Mean WBC counts and CRP levels were higher in women with proven AA than in those of control groups (all p < 0.05. Among all the groups, the median NLR and PLR were significantly different in women with proven AA (all p < 0.05. Receiver operating characteristic analysis was used to determine cut-off values for WBC count, CRP, lymphocyte count, NLR and PLR, and multiple logistic regression analysis showed that NLR and PLR used with routine methods could diagnose AA with 90.5% accuracy. Used in addition to routine diagnostic methods, NLR and PLR increased the accuracy of the diagnosis of AA in pregnant women.

  12. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as predictors of wound healing failure in head and neck reconstruction.

    Science.gov (United States)

    Maruyama, Yoko; Inoue, Keita; Mori, Keita; Gorai, Katsuya; Shimamoto, Ryo; Onitsuka, Tetsuro; Iguchi, Hiroyoshi; Okazaki, Mutsumi; Nakagawa, Masahiro

    2017-01-01

    In microsurgical head and neck reconstruction, a higher rate of post-operative wound complication could be predicted by a lower pre-operative neutrophil ratio (wound complications in microsurgical head and neck reconstruction. Patients who were undergoing tumor ablation and microsurgical reconstruction from April 2011 to March 2014 were analyzed retrospectively. The pre-operative hematological data, age, sex, co-morbidities, body mass index (BMI), adjuvant therapies, smoking, operation time, blood loss, total protein, T-stage, and Anesthesiologists Performance Status (ASA-PS) score were collected. Cases of post-operative wound healing failure were reviewed. One hundred and three consecutive patients were enrolled. Among these, the results of 77 patients who were younger than 70 years of age were analyzed. The distributions of the neutrophil ratio (p = .0005), lymphocyte ratio (p = .0166), monocyte ratio (p = .0341), NLR (p = .005), and PLR (p = .008) differed significantly between the patients with and without post-operative wound healing failure. Neutrophil ratio, NLR, and PLR cut-off values of 64.9, 3.5, and 160 were significantly associated with the rate of wound healing failure rate (p = .0002, .00021, .0042, respectively).

  13. Neutrophil to lymphocyte with monocyte to lymphocyte ratio and white blood cell count in prediction of lung cancer

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    Thang Thanh Phan

    2018-04-01

    Full Text Available Background Lung cancer is the most common cause of cancer deaths in both sexes, while it is very difficult for screenings and early detection. Aims This study aims to clarify the role of systematic inflammation markers, including white blood cell (WBC, neutrophil (NEU, monocyte (MONO, platelet (PLT, neutrophil to lymphocyte ratio (NLR, monocyte to lymphocyte ratio (MLR and platelet to lymphocyte ratio (PLR in prediction of lung cancer. Methods A case-control study was conducted on 1,315 primary lung cancer patients and 1,315 healthy adults with matched age and gender at Cho Ray hospital. NLR, MLR and PLR were calculated by using neutrophil, lymphocyte, monocyte and platelet count which were recalled from laboratory database. With 600 cases in the derivation set, the logistic regression with univariate analysis was used to identify the impacted marker, then developing the optimal prediction model for lung cancer by logistic regression with multivariate method. The diagnostic values of optimal model consisting of sensitivity (Sen, specificity (Spe, positive predictive value (PPV, negative predictive value (NPV and the area under the ROC curve (AUC value were extracted and verified on all data, in validation set. Results The median values of WBC, NEU, MONO, PLT, NLR, MLR and PLR in lung cancer were not significantly difference between histological subtypes and clinical stages (p > 0.05, but higher than the values in control group (p < 0.01. Multivariates analysis shows that NLR, MLR and WBC were three parameters that have the significant impact of the optimal prediction model (p < 0.01. The AUC value, sensitivity and specificity of the optimal model for lung cancer detection were 0.881, 73.5 per cent (95 per cent CI:70.3–76.6 and 87.7 per cent (95 per centCI:85.2–89.9, respectively. Whereas, the PPV and NPV values of prediction model were 85.7 per cent (95 per cent CI:82.8–88.2 and 76.8 (95 per centCI:73.9–79.5, respectively. Among three

  14. The effect of smoking on neutrophil/lymphocyte and platelet/lymphocyte ratio and platelet ındices: a retrospective study.

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    Tulgar, Y K; Cakar, S; Tulgar, S; Dalkilic, O; Cakiroglu, B; Uyanik, B S

    2016-07-01

    Smoking commonly leads to death. Although the neutrophil/lymphocyte Ratio, platelet/lymphocyte ratio and platelet indices have been shown to be important for the diagnosis, prognosis and severity of some diseases, the smoking status of patients in these studies has not been well defined. In this study, we compared ratios derived from complete blood count and platelet indices to smoking status and length in smokers and non-smokers. The data of healthy males and females aged between 18-60 years who presented to our institute for a routine check-up were collected, and subjects were divided in two groups - smokers and non-smokers. The presence of medical history or laboratory results which could affect inflammatory response, formed our exclusion criteria. All complete blood count results were noted and persons' smoking habits were calculated as pack/years. White blood cell, neutrophil, basophil and eosinophil counts; mean corpuscular volume, red cell distribution width and neutrophil/lymphocyte ratio were significantly higher in smokers when compared to non-smokers (psmokers were grouped according to smoking habits; positive linear correlations were detected between pack/year and Neutrophil/lymphocyte ratio and also pack/year and plateletcrit in smokers (paffected and platelet distribution width is increased in smokers. If smokers are not excluded from studies evaluating neutrophil/lymphocyte ratio and platelet distribution width, the relationship between smoking status as well as pack/year must be determined and reported.

  15. Relationship between Neutrophil-to-Lymphocyte Ratio and Prognosis in Patients with Deep Neck Space Infection

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    Engin Şengül

    2016-03-01

    Full Text Available Objective: The aim of this study was to demonstrate if there is any relation between the neutrophil-to-lym­phocyte ratio and prognosis in patients with deep neck space infections Methods: One hundred eight patients who were interned and treated due to deep neck infection in department of otolaryngology between January 2010 and January 2015 were analyzed. Demographics, clini­cal data, complications and treatment results of patients were evaluated. Pediatric patients between the age of 0 and 14, the patients who had only peritonsillary abscess, infection secondary to trauma were excluded from study. During follow-up and treatment duration the patients with deep neck infections were divided into two groups ac­cording to whether they had any complication (group 1 or not (group 2. Results: Fourteen (13% patients with deep neck in­fections had life-threatening complications whereas 94 (87% did not have any complication during follow-up and treatment duration. The mean neutrophil-to-lymphocyte ratio in patients with complications was significantly high­er than the patients without any complications (p0.05. Conclusion: This study showed that the neutrophil-to-lymphocyte ratio can be used as a cheap, easily obtained and predictive prognostic factor in patients with deep neck infections.

  16. Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure

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    Argan, Onur; Ural, Dilek; Kozdag, Guliz; Sahin, Tayfun; Bozyel, Serdar; Aktas, Mujdat; Karauzum, Kurtulus; Yılmaz, Irem; Dervis, Emir; Agir, Aysen

    2016-01-01

    Background Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. Material/Methods Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). Results Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; pfailure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001). Conclusions Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction. PMID:27918494

  17. The neutrophil-lymphocyte ratio in children with atopic dermatitis: a case-control study.

    Science.gov (United States)

    Dogru, M; Citli, R

    2017-01-01

    Neutrophil-lymphocyte ratio(NLR) is a novel marker for the evaluation of inflammation and has not been evaluated previously in patients with AD. To investigate the relationship between NLR and the clinical findings of AD. Sixty-six children with AD were included in the study.The control group was included 66 children who have no allergic and chronic diseases.The immunoglobulin(Ig)E levels and complete blood count were measured. Skin prick tests were performed using the same antigens for all patients. NLR was not significant between the patient and control groups (p>0.05).The patients with AD were divided into 3 groups according to their SCORAD score as mild, moderate and severe AD.No statistically significant difference was present between groups in terms of demographic and clinical characteristics,eosinohil-lymphocyte ratio,eosinophil-neutrophil ratio,the percentage of eosinophil, IgE,the sensitivity of skin tests(p>0.05). However,NLR and sensitivity to house dust mite were significantly different among groups(respectively,p=0.037,p:0.043).SCORAD scores were weak positively correlated with NLR levels,eosinophil-lymphocyte ratio and the sensitivity of house dust mite (respectively,r:0.329;p:0.007,r:0.264;p:00035,r:0.325;p:0.008). We didn't found significant difference in term of mean NLR betweeen patients with AD and control group. NLR was found significantly higher in severe AD patients than mild AD patients.The house dust mite sensitivity, eosinohil-lymphocyte ratio and NLR were correlated with AD severity.

  18. Leukocytic Response and Peripheral Venous Blood Lymphocyte Apoptosis as a Marker of Tissue Ischemia in Acute Massive Blood Loss

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    N. V. Borovkova

    2013-01-01

    Full Text Available Objective: to estimate the level of peripheral venous blood lymphocyte apoptosis and intraoperative hypoxia in victims with acute massive blood loss. Subjects and methods. Twenty-two patients with open and close chest and abdominal traumas complicated by acute massive blood loss were examined. All the patients were emergently operated on to stop bleeding. Tissue metabolism was evaluated from gases, acid-base parameters, and plasma lactate, glucose, potassium, and sodium levels. Apoptosis of mononuclear cells was studied and dead leukocytes were counted using flow cytometry. Results. Preoperatively, the victims were found to have venous hypoxemia, hyperlactatemia, hyperglycemia, moderate leukocytosis, and higher dead leukocyte counts. There were also raised counts of lymphocytes coming into the process of apoptosis. A significant relationship was found between monocyte counts and hypoxia values. At the end of surgery, oxygen balance values became stable and exerted an effect on the count of leukocytes, the relative level of granulocytes, the relative and absolute counts of dead and damaged leukocytes, and the concentration of lymphocytes in the victims’ venous blood during the early stages of apoptosis, as evidenced by nonlinear regression models. Conclusion. The indicators of immunocompetent cell apoptosis and the count of venous blood dead leukocytes along with lactate levels and venous hypoxemia parameters reflect the degree of tissue hypoxia and may be used as specific markers.

  19. Postoperative neutrophil-to-lymphocyte ratio of living-donor liver transplant: Association with graft size

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    Hironori Hayashi

    2016-04-01

    Full Text Available Issues related to small-for-size grafts in living donor liver transplantation (LDLT are highly important. The neutrophil lymphocyte ratio (NLR has been reported to be an inexpensive index of systemic inflammation for various diseases. We retrospectively evaluated the relationship between NLR and clinical course of 61 adult LDLT recipients in our institute until post-operative day 14. Patients were classified into two groups based on the graft volume divided by standard liver volume, as over 35% of graft volume divided by standard liver volume (GV/SLV (Group L; n = 55 and under 35% of GV/SLV (Group S; n = 6. No differences were seen in background of the patients between the two groups. Also, absolute neutrophil, lymphocyte and platelet counts in both the groups showed no significant differences. In contrast, the NLR between the groups differed significantly from post-operative day 3 to 10, being higher in the Group S. In addition, the incidence of prolonged hyperbilirubinemia and small for size graft syndrome differed significantly between the two groups. Therefore, the elevation of post-operative NLR in the smaller graft group reflect suggestive pathophysiology of endothelial injuries that related to small for size graft syndrome in LDLT.

  20. Clinical Significance of Preoperative Neutrophil Lymphocyte Ratio versus Platelet Lymphocyte Ratio in Patients with Small Cell Carcinoma of the Esophagus

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    Ji-Feng Feng

    2013-01-01

    Full Text Available Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various of cancers. The aim of this study was to determine the prognostic values of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR in patients with small cell carcinoma of the esophagus (SCCE. Preoperative NLR and PLR were evaluated in 43 patients with SCCE from January 2001 to December 2010. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. Receiver operating characteristic (ROC curves were also plotted to verify the accuracy of NLR and PLR for survival prediction. Patients with PLR ≥150 had significantly poorer (relapse-free survival RFS and (overall survival OS compared to patients with PLR <150. However, RFS or OS did not differ according to NLR categories (<3.5 and ≥3.5. The areas under the curve (AUC indicated that PLR was superior to NLR as a predictive factor. The results of the present study conclude that PLR is superior to NLR as a predictive factor in patients with SCCE.

  1. Persistent elevation of postoperative neutrophil-to-lymphocyte ratio: A better predictor of survival in gastric cancer than elevated preoperative neutrophil-to-lymphocyte ratio.

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    Min, Kyueng-Whan; Kwon, Mi Jung; Kim, Dong-Hoon; Son, Byoung Kwan; Kim, Eun-Kyung; Oh, Young Ha; Wi, Young Chan

    2017-10-25

    Postoperative neutrophil-to-lymphocyte ratio change (NLRc) reflects the dynamic change of balance between host inflammatory response and immune response after treatment. In gastric cancer, an elevated initial NLR (iNLR) is reported to be a prognostic predictor, but the clinical application of the NLRc remains unclear. The NLRc was assessed in 734 patients undergoing total/subtotal gastrectomy and endoscopic submucosal dissection for gastric adenocarcinoma. The iNLR and NLRc were recorded within 10 days of the first diagnosis and 3-6 months after surgery, respectively. Using receiver operating characteristic (ROC) curves, we investigated the relationship between NLRc or iNLR and patient survival. The analysis revealed a higher predictive power for correlating patient survival with the NLRc compared with iNLR. NLRc was defined as negative (lower than iNLR) and positive (higher than iNLR). A positive NLRc was frequently observed in patients with advanced AJCC stage, local recurrence, distant metastasis, perineural invasion, and adjuvant chemotherapy (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between patient survival and NLRc (all p < 0.05) but no association between survival and iNLR. The NLRc could be a better indicator than iNLR for predicting survival in patients with gastric cancer.

  2. Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery.

    Science.gov (United States)

    Chowdhary, Mudit; Switchenko, Jeffrey M; Press, Robert H; Jhaveri, Jaymin; Buchwald, Zachary S; Blumenfeld, Philip A; Marwaha, Gaurav; Diaz, Aidnag; Wang, Dian; Abrams, Ross A; Olson, Jeffrey J; Shu, Hui-Kuo G; Curran, Walter J; Patel, Kirtesh R

    2018-05-30

    Neutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocyte-predominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain metastases (BM). BM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan-Meier method and cumulative incidence with competing risk for death, respectively. 188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR > 6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. > 6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR > 6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03-2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30-2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes. Post-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.

  3. Correlation between the neutrophil-lymphocyte count ratio and bacterial infection in patient with human immunodeficiency virus

    Science.gov (United States)

    Kusnadi, D.; Liwang, M. N. I.; Katu, S.; Mubin, A. H.; Halim, R.

    2018-03-01

    Parameters for starting antibiotic therapy such as CRP andleukocytosis are considered non-specific. Previous studies have shown the Neutrophil-Lymphocyte Count Ratio (NLCR) can serve as the basis of bacterial infection, the level of infection, and the basis of antibiotic therapy. Compared with the Procalcitonin parameter, this NLCR is rapid, an inexpensive and requires no additional sampling. To determine the correlation between The Neutrophil-LymphocyteCount Ratio to bacterial infection in HIV patients. This study was a cross-sectional observational approach to HIV subject at Wahidin Sudirohusodo and Hasanuddin University Hospital. The subjects performed routine blood, microbiology test,and blood Procalcitonin levels tests. Then performed NLCR calculations based on routine blood results. The subjects then grouped the presence or absence of bacterial infection.In 146 study subjects, there were 78 (53.4%) with bacterial infections and 68 (46.6%) without bacterial infection as controls. Subjects with bacterial infections had higher total neutrophils (84.83) compared with non-bacterial infections. Subjects with bacterial infections had total lymphocytes with an average of 8.51 lower than non-bacterial infections. Subjects with bacterial infections had higher NLCR values with an average of 12.80. The Neutrophil-Lymphocyte Count Ratio can become a marker of bacterial infection in HIV patients.

  4. New Predictive Parameters of Bell"s Palsy: Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio

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    Doğan Atan

    2015-06-01

    Full Text Available Background: Bell’s palsy is the most frequent cause of unilateral facial paralysis. Inflammation is thought to play an important role in the pathogenesis of Bell’s palsy. Aims: Neutrophil to lymphocyte ratio (NLR and platelet to lymphocyte ratio (PLR are simple and inexpensive tests which are indicative of inflammation and can be calculated by all physicians. The aim of this study was to reveal correlations of Bell’s palsy and degree of paralysis with NLR and PLR. Study Design: Case-control study. Methods: The retrospective study was performed January 2010 and December 2013. Ninety-nine patients diagnosed as Bell’s palsy were included in the Bell’s palsy group and ninety-nine healthy individuals with the same demographic characteristics as the Bell’s palsy group were included in the control group. As a result of analyses, NLR and PLR were calculated. Results: The mean NLR was 4.37 in the Bell’s palsy group and 1.89 in the control group with a statistically significant difference (p<0.001. The mean PLR was 137.5 in the Bell’s palsy group and 113.75 in the control group with a statistically significant difference (p=0.008. No statistically significant relation was detected between the degree of facial paralysis and NLR and PLR. Conclusion: The NLR and the PLR were significantly higher in patients with Bell’s palsy. This is the first study to reveal a relation between Bell’s palsy and PLR. NLR and PLR can be used as auxiliary parameters in the diagnosis of Bell’s palsy.

  5. The neutrophil-to-lymphocyte ratio as disease actvity marker in multiple sclerosis and optic neuritis

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    Bisgaard, A K; Pihl-Jensen, G; Frederiksen, J L

    2017-01-01

    BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). The neutrophil-to-lymphocyte ratio (NLR) has been identified as a disease activity marker in several diseases. We aim to evaluate the significance of the NLR in the different subtypes of MS......, optic neuritis (ON) and in relation to disease activity and Expanded Disability Status Scale (EDSS). METHODS: We included 378 patients and 813 healthy controls (HC) from The Nordic Reference Interval Project 2000 (NORIP). Complete blood count, demographic and clinical data from patients were evaluated...... between NLR and time of blood sampling. Logistic regression models were constructed for EDSS ≥ 4.0 as outcome. RESULTS: The NLR was significantly higher (p higher NLR (p

  6. Diagnostic value of procalcitonin, CRP, leukocytes and BAL neutrophils for pulmonary complications in the immunocompromised host

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    Daiana Stolz

    2006-12-01

    Full Text Available We evaluated the diagnostic accuracy of laboratory biomarkers and BAL differential cell count for the diagnosis of bacterial infection in severe immunosuppressed patients. One-hundred and seven consecutive patients undergoing bronchoscopy for suspected pulmonary infection were included in this study. Assessment included history, clinical examination, chest image studies, CRP, procalcitonin (ProCT, leukocyte counts, and BAL results. Patients were classified as having proven, possible, and non-bacterial infection.

  7. Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

    Science.gov (United States)

    Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Céline; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel Njweipi; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire

    2018-03-27

    The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 10 6 /ml and 2.48 × 10 6 /ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

  8. The relation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume with the presence and severity of Behçet's syndrome

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    Sevil Alan

    2015-12-01

    Full Text Available Behçet's syndrome (BS is associated with chronic inflammation and endothelial dysfunction. Although there have been extensive investigations on neutrophil-to-lymphocyte ratio (NLR, platelet-to-lymphocyte ratio (PLR, and mean platelet volume (MPV in many diseases, their roles in BS is unclear. The purpose of the present study was to evaluate NLR, PLR, and MPV levels in BS patients and explore their clinical significance. The study included 254 patients with BS and 173 healthy individuals. Age, sex, age of onset, duration of disease, smoking, Behçet activity score, total white blood counts, neutrophil, platelet, and T lymphocyte counts of the patients were recorded. White blood cell (WBC, neutrophil, platelet, NLR, and PLR were significantly higher in patients with BS when compared with healthy controls (all p  0.05. In the BS group, PLR and MPV were significantly different among the three severity groups (p = 0.037 and p = 0.016, respectively. We showed that any laboratory markers were not associated with joint, eye, central nervous system, large vessel, or gastrointestinal involvement in BS. NLR was shown to be an independent factor for BS by multivariate analysis. We suggest that NLR can be considered to be a diagnostic criterion of BS given the support of the findings from larger prospective studies.

  9. Leukocyte Profile in Peripheral Blood and Neutrophil-Lymphocyte Ratio in Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Miller, Iben Marie; Ring, Hans Christian; Prens, Errol P.

    2016-01-01

    odds of leukocytosis when compared to controls with an odds ratio for the HS-HOSP group of 4.38 (95% CI = 2.18-8.80; p ... profile in hospital-treated HS patients (HS-HOSP), self-reported population-based HS patients (HS-POP) and population controls. Results: Our study comprised 32 individuals in the HS-HOSP group, 430 in the HS-POP group, and 20,780 controls. The median hs-CRP for the HS-HOSP group was 5.1 mg/l (quartile...... range 2.6-8.2), 2.2 mg/l (1.0-4.3) for the HS-POP group and 1.3 mg/l (0.7-2.9) for the controls. An age-sex-adjusted analysis revealed a significantly higher hs-CRP for both HS groups compared to controls (p

  10. Is combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma?

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    Tanoglu A

    2014-03-01

    Full Text Available Alpaslan Tanoglu,1 Ergenekon Karagoz,2 Nurettin Yiyit,3 Ufuk Berber4 1Department of Gastroenterology, 2Department of Infectious Diseases and Clinical Microbiology, 3Department of Thoracic Surgery, 4Department of Pathology, GATA Haydarpasa Training Hospital, Uskudar, TurkeyWe read with interest the recent article entitled "Combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma" by Feng et al.1 In their study, authors aimed to investigate the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR, for predicting survival in patients with esophageal squamous cell carcinoma (ESCC. Finally, they concluded that combination of NLR and PLR is a useful predictor of postoperative survival in patients with ESCC and combination of these parameters is superior to NLR or PLR as a predictive factor in patients with ESCC. We would like to thank the authors for their contribution.View original paper by Feng and colleagues.

  11. The Neutrophil to Lymphocyte Ratio May Predict Benefit from Chemotherapy in Lung Cancer

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    Dan Liu

    2018-04-01

    Full Text Available Background/Aims: The objectives of this study were to evaluate the impact of the neutrophil to lymphocyte ratio (NLR and platelet to lymphocyte ratio (PLR on overall survival (OS and to explore the value of changes in the NLR and PLR with treatment as a response indicator. Methods: A total of 934 patients were eligible for retrospective analysis between 2008 and 2014. The pretreatment and post-treatment PLR and NLR in all patients were calculated based on complete blood counts. Univariate and multivariate Cox regression analyses were performed to determine the associations of the PLR and NLR with OS. Results: The pretreatment NLR and PLR were correlated with different disease status and response to chemotherapy. Patients with lower NLR and PLR had a significantly better complete response (CR rate to chemotherapy versus those with a higher NLR and PLR (p< 0.001. The NLR and PLR were sustained in patients who obtained a CR compared with moderate or poor response patients. The lower NLR of pretreatment was independently associated with a favourable prognosis in whole patients with lung cancer (HR: 0.69, 95% CI, 0.55-0.85, p< 0.001. In the patients under control after chemotherapy, the NLR of post-chemotherapy had a greater impact on survival, and the low NLR level maintained during chemotherapy was identified a predictor for favourable survival. PLR was not an independent prognostic indicator in the whole cohort or any subgroups. Conclusion: Our results suggested that NLR was well-connected with outcomes and response to chemotherapy in patients with lung cancer. As a response indicator, NLR may predict benefit from chemotherapy and improve patient selection.

  12. Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes cultured in synovial fluid isolated from patients with rheumatoid arthritis

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    Michał Gajewski

    2016-07-01

    Full Text Available Objectives : Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca 2+ ions mobilization or β 2 -integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods : Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils or with or without synovial fluid (85% for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH vs. oxidized glutathione (GSSG ratio and membrane lipid peroxidation evaluation. Results : Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions : Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by

  13. Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Patients with Cutaneous Vasculitis.

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    Emiroglu, Nazan; Cengiz, Fatma Pelin; Bahalı, Anıl Gulsel; Ozkaya, Dilek Biyik; Su, Ozlem; Onsun, Nahide

    2017-03-01

    Vasculitis represents a specific pattern of inflammation of the blood vessel wall that can occur in any organ system of the body. The neutrophil to lymphocyte ratio (NLR) and red blood cell distribution width (RDW) are currently used as markers of inflammation in several diseases. This study analyzed C-reactive protein level (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), NLR, and RDW in patients who had cutaneous vasculitis, or cutaneous vasculitis with systemic involvement, and in healthy controls. A total of 85 individuals were included in our study: 45 with vasculitis and 40 healthy controls. Patients who had complete blood count (CBC) analysis, CRP, and ESR at the time of skin biopsy were included in the study. NLR was calculated from these parameters. NLR, CRP, ESR, and WBC were significantly higher in patients with vasculitis than in healthy controls (p≤0.05), but RDW did not significantly differ between the two groups. This study suggests that blood NLR may be used for predicting vasculitis, especially cutaneous vasculitis with systemic involvement. © 2017 by the Association of Clinical Scientists, Inc.

  14. Preoperative neutrophil-lymphocyte ratio is an independent prognostic factor for hepatocellular carcinoma after radical resection

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    ZHANG Tingting

    2015-06-01

    Full Text Available ObjectiveTo evaluate the effect and predictive value of preoperative neutrophil-lymphocyte ratio (NLR on the prognosis of patients undergoing radical resection for hepatocellular carcinoma (HCC. MethodsThe clinical data of 245 patients who received radical resection for HCC in our hospital from 2004 to 2009 were retrospectively analyzed. The effects of clinicopathological parameters including NLR on overall survival (OS time were assessed by univariate analysis using the log-rank test. The significant variables were further analyzed by multivariate analysis using the Cox regression model. ResultsUsing NLR=1.5, 2, and 3 as cut-off points, the patients were divided into four groups. The median OS time in groups with NLR<1.5, 1.5≤NLR<2, 2≤NLR<3, and NLR≥3 was 39.6, 38.3, 25.4, and 19.9 months, respectively (P=0.003. Multivariate analysis showed that preoperative NLR, levels of alpha-fetoprotein and alanine aminotransferase in peripheral blood, number of tumor nodules, maximum size of tumor, and portal vein tumor thrombus were independent prognostic factors for HCC (P<0.05. ConclusionPreoperative NLR in peripheral blood is a novel prognostic biomarker for HCC after radical resection.

  15. Association of pretreatment neutrophil-lymphocyte ratio and outcome in emergency colorectal cancer care.

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    Palin, R P; Devine, A T; Hicks, G; Burke, D

    2018-04-01

    Introduction The association between the neutrophil-lymphocyte ratio (NLR) and outcome in elective colorectal cancer surgery is well established; the relationship between NLR and the emergency colorectal cancer patient is, as yet, unexplored. This paper evaluates the predictive quality of the NLR for outcome in the emergency colorectal cancer patient. Materials and Methods A total of 187 consecutive patients who underwent emergency surgery for colorectal cancer were included in the study. NLR was calculated from the haematological tests done on admission. Receiver operating characteristic analyses were used to determine the most suitable cut-off for NLR. Outcomes were assessed by mortality at 30 and 90 days using stepwise Cox proportional hazards regression. Results An NLR cut-off of 5 was found to have the highest sensitivity and specificity. At 30 days, age and time from admission to surgery were associated with increased mortality; a high NLR was associated with an increased risk of mortality in univariate but not multivariate analysis. At 90 days, age, NLR, time from admission to surgery and nodal status were all significantly associated with increased mortality on multivariate analysis. Conclusions Pre-operative NLR is a cheap, easily performed and useful clinical tool to aid prediction of outcome in the emergency colorectal cancer patient.

  16. Neutrophil-to-lymphocyte ratio in patients with peripheral vertigo: a prospective controlled clinical study.

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    Ozbay, Isa; Kahraman, Cuneyt; Balikci, Hasan Huseyin; Kucur, Cuneyt; Kahraman, Nilufer Kuzeyli; Ozkaya, Derya Pınar; Oghan, Fatih

    2014-01-01

    We aimed to investigate the relationship between peripheral vertigo and inflammation by using the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory marker. We recruited 103 patients with peripheral vertigo (71 women, 32 men; mean age, 39.8 ± 14.7 years) who presented to the Otolaryngology Department of Dumlupinar University Hospital. Vertigo patients with systemic diseases, neurological disorders, malignancy or any inflammatory disease that could alter the NLR were excluded from the study. We also enrolled 103 age- and sex-matched healthy subjects (controls; 82 women, 21 men; mean age, 36.7 ± 13.5 years) who underwent routine checkups in our hospital. The vertigo patients underwent full otolaryngologic and neurologic examinations and audiometric tests to rule out any other pathology causing the peripheral vertigo. NLR was calculated in all subjects and was compared between the patient and control groups. There were no significant differences between the study and control groups in terms of lipid profiles, liver-function tests, white blood cell (WBC) count, hemoglobin level, mean platelet volume, and vitamin B12 and folate levels. The mean NLR was significantly higher in the patients than in the controls (Pvertigo, found that the NLR is significantly higher among peripheral vertigo patients than among healthy controls. This result suggests that the NLR is a novel potential marker of stress in peripheral vertigo patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Neutrophil to lymphocyte ratio as the main predictor of peripheral artery disease in regular hemodialysis patients

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    Siregar, R. H.; Muzasti, R. A.

    2018-03-01

    Cardiovascular disease is the most inducer of morbidity and mortality of chronic kidney disease (CKD) patients who have undergone dialysis. Today, neutrophil to lymphocyte ratio (NLR) is considered an indicator of the severity and extent of systemic inflammation and atherosclerosis in patients with renal and cardiovascular disorders. To examine the relationship between NLR with PAD in regular hemodialysis patients, a cross-sectional study, Ankle- Brachial Index (ABI) measurement and peripheral blood examination was on 72 regular hemodialysis patients ≥6 months. The ABI value ≤0.9 is considered PAD. NLR≥ 3.5 is considered abnormal based on some pre-existing research. Prevalence of PAD is 29.16%. Chi- square test showed significant correlation between NLR with PAD (p = 0.0001), multiplication of Calcium and Phosphorus (p = 0.0001), and type 2 Diabetes Mellitus (T2DM) (p = 0.039), multivariate analysis showed that NLR was an independent predictor for PAD in regular hemodialysis patients (RR = 2.271 p = 0.027). In conclusion, NLR, a new inflammatory marker of peripheral blood examination may serve as a marker of PAD in a regular hemodialysis patient, in addition to the multiplication of Calcium and Phosphorus as well as T2DM.

  18. Postoperative Elevation of the Neutrophil: Lymphocyte Ratio Predicts Complications Following Esophageal Resection.

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    Vulliamy, Paul; McCluney, Simon; Mukherjee, Samrat; Ashby, Luke; Amalesh, Thangadorai

    2016-06-01

    Complications following esophagectomy are a significant source of morbidity. The aim of this study was to investigate the utility of the neutrophil:lymphocyte ratio (NLR) in the early identification of complications following esophagectomy, as compared to other routinely available parameters. We performed a retrospective cohort study of patients undergoing Ivor-Lewis esophagectomy at a single centre. Baseline characteristics and complications occurring within the first 30 days of surgery were recorded. White blood cell counts and C-reactive protein (CRP) levels immediately following surgery (day 0) and over the subsequent three postoperative days were analysed. Sixty-five patients were included, of whom 29 (45 %) developed complications. The median NLR was similar among patients with and without a complicated recovery on day 0 (12.7 vs 13.6, p = 0.70) and day 1 (10.0 vs 9.3, p = 0.29). Patients who subsequently developed complications had a higher NLR on day 2 (11.8 vs 7.5, p 8.3 on day 2 had a sensitivity of 93 % and a specificity of 72 % for predicting complications. The NLR is a simple and routinely available parameter which has a high sensitivity in the early detection of complications following esophagectomy.

  19. Predictive value of neutrophil-to-lymphocyte ratio in diabetic wound healing.

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    Vatankhah, Nasibeh; Jahangiri, Younes; Landry, Gregory J; McLafferty, Robert B; Alkayed, Nabil J; Moneta, Gregory L; Azarbal, Amir F

    2017-02-01

    The neutrophil-to-lymphocyte ratio (NLR) has been used as a surrogate marker of systemic inflammation. We sought to investigate the association between NLR and wound healing in diabetic wounds. The outcomes of 120 diabetic foot ulcers in 101 patients referred from August 2011 to December 2014 were examined retrospectively. Demographic, patient-specific, and wound-specific variables as well as NLR at baseline visit were assessed. Outcomes were classified as ulcer healing, minor amputation, major amputation, and chronic ulcer. The subjects' mean age was 59.4 ± 13.0 years, and 67 (66%) were male. Final outcome was complete healing in 24 ulcers (20%), minor amputation in 58 (48%) and major amputation in 16 (13%), and 22 chronic ulcers (18%) at the last follow-up (median follow-up time, 6.8 months). In multivariate analysis, higher NLR (odds ratio, 13.61; P = .01) was associated with higher odds of nonhealing. NLR can predict odds of complete healing in diabetic foot ulcers independent of wound infection and other factors. Copyright © 2016 Society for Vascular Surgery. All rights reserved.

  20. Neutrophil-to-Lymphocyte Ratio in the Prediction of Microscopic Colitis

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    Feyzullah Ucmak

    2016-01-01

    Full Text Available Aim: The aim of this study was to investigate the importance of the neutrophil-to-lymphocyte ratio (NLR in predicting microscopic colitis (MC in patients with diarrhea-dominant type irritable bowel syndrome (IBS-D. Material and Method: Between January 1, 2010 and December 31, 2012, 49 patients who fulfilled the Roma III criteria for IBS-D were included in the study. All patients had underwent colonoscopy and colonoscopic biopsy (cecum, ascending, transverse, descending and rectosigmoid sections to diagnose MC (25 patients with MC. Complete blood count parameters were evaluated in the two groups (IBS-D and MC using standard methodology. Results: The patients were evaluated in two groups: MC and IBS-D. The groups were similar with respect to age, gender and presence of hypertension. The NLO was significantly higher in the MC group compared to the IBS-D group (2.48±0.99, 1.92±0.84; p=0.041, respectively. A cut-off value of 1.86 had a sensitivity of 76% and spesificity of 55% in predicting MC in patients with symptoms of IBS-D. Discussion: A significant association was found between the presence of MC in patients with IBS-D and increased NLR. The NLR may be a useful marker in predicting MC in patients with symptoms of IBS-D.

  1. Diagnostic Accuracy of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Detecting Occult Papillary Thyroid Microcarcinomas in Benign Multinodular Goitres

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    Dimitrios K. Manatakis

    2018-01-01

    Full Text Available Objective. To investigate the diagnostic accuracy of neutrophil-to-lymphocyte (NLR and platelet-to-lymphocyte (PLR ratios in detecting occult papillary thyroid microcarcinomas in benign, multinodular goitres. Methods. 397 total thyroidectomy patients were identified from the institutional thyroid surgery database between 2007 and 2016 (94 males, 303 females, mean age 53 ± 14.5 years. NLR and PLR were calculated as the absolute neutrophil and absolute platelet counts divided by the absolute lymphocyte count, respectively, based on the preoperative complete blood cell count. Results. NLR was significantly higher in carcinomas and microcarcinomas compared to benign pathology (p=0.026, whereas a direct association could not be established for PLR. Both NLR and PLR scored low in all parameters of diagnostic accuracy, with overall accuracy ranging between 45 and 50%. Conclusions. As surrogate indices of the systemic inflammatory response, NLR and PLR are inexpensive and universally available from routine blood tests. Although we found higher NLR values in cases of malignancy, NLR and PLR cannot effectively predict the presence of occult papillary microcarcinomas in otherwise benign, multinodular goitres.

  2. Neutrophil-lymphocyte ratio: a new predictive and prognostic factor in patients with Bell palsy.

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    Özler, Gül Soylu; Günak, Güldem

    2014-05-01

    The aim of this study was to investigate whether neutrophil-lymphocyte ratio (NLR) levels are elevated in patients with Bell palsy (BP). Moreover, we aimed to find out whether there is a correlation between NLR levels and the severity and prognosis of BP. The study group consisted of 25 subjects who presented with BP and 25 control subjects with no evidence of facial nerve pathology. The subjects underwent a general physical examination; an assessment of laboratory blood parameters; and a cranial magnetic resonance imaging, using gadolinium as a contrast medium. The mean (SD) NLR values were 2.16 (0.80) in the patients with BP and 1.36 (0.48) in the control group. The mean NLR values in the patients with BP were significantly higher than in the control group (P = 0.0001). There was a positive correlation between NLR values and grade of facial paralysis (r = 0.661, P = 0.0001). The mean (SD) NLR values in the grades III, IV, V, and VI BP groups were 1.40 (0.54), 1.78 (0.44), 3.00 (0.63), and 2.60 (0.54), respectively. The mean NLR values in the grade V BP group were significantly higher than in the other groups (P = 0.0001). In addition, there was a positive correlation between NLR values and prognosis of facial paralysis (r = 0.239, P = 0.251). There is no previous study that investigated the association between NLR and BP in the literature. Higher NLR values in patients with BP may be a predictor of worse prognosis.

  3. Propensity score analysis of recurrence for neutrophil-to-lymphocyte ratio in colorectal cancer.

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    Balde, Alpha I; Fang, Suzhen; He, Linyun; Cai, Zhai; Han, Shuai; Wang, Weiwei; Li, Zhou; Kang, Liang

    2017-11-01

    The perioperative serum neutrophil-to-lymphocyte ratio (NLR) has been proposed to predict adverse prognosis in colorectal cancer (CRC). However, its interpretation remains unclear. The present study aimed to clarify the prognostic value of NLR in predicting survival among CRC patients. A single-centre, retrospective, propensity score-matched study of adenocarcinoma patients who underwent D3 lymphadenectomy via laparoscopic or open surgery between 2010 and 2016 was conducted. A cutoff of 3.5 was used based on the receiver operating characteristic curve. To overcome selection biases, we performed a 1:1 match using six covariates. The high-preoperative NLR group had a higher recurrence rate than the low group (P analysis showed that increased NLR (P analysis showed that N2 (hazard ratio [HR], 2.492; P = 0.008) was an adverse prognostic factor for RFS. Univariate analysis for overall survival (OS) revealed that high perioperative NLR (P = 0.001), N1 (P = 0.01), N2 (P analysis showed that M1 (HR, 3.973; P < 0.001) and N2 (HR, 2.381; P = 0.013) were highly adverse factors for OS. Clinical assessments performed during a 21.14 (±16.20)-mo follow-up revealed that OS (P = 0.001) and RFS (P < 0.001) were worse in the high-perioperative group than in the low group between the matched groups. An elevated preoperative NLR is a strong predictor of worse RFS and OS in CRC patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Association of Neutrophil-to-Lymphocyte Ratio With Inflammation and Erythropoietin Resistance in Chronic Dialysis Patients

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    Jérôme Pineault

    2017-11-01

    Full Text Available Background: Neutrophil-to-lymphocyte ratio (NLR was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in nephrology is not yet established. Objective: We evaluated its accuracy as an inflammation biomarker in a dialysis population. Design setting: Single-center retrospective study. Patients: The records of all 550 patients who were treated with hemodialysis (HD or peritoneal dialysis (PD from September 2008 to March 2011 were included. Measurements: NLR was calculated from the monthly complete blood count. Methods: Association between NLR and markers of inflammation (C-reactive protein [CRP], serum albumin, and erythropoietin resistance index [ERI] was measured using Spearman coefficient. Results: In total, 120 patients were eligible for the correlation analyses. We found a positive correlation between NLR and CRP (all patients: r = 0.45, P < .001; HD: r = 0.47, P < .001; PD: r = 0.48, P = .13. NLR and albumin were inversely correlated ( r = −0.51, P < .001. Finally, high NLR was associated with a nonsignificant increased ERI, but we have not demonstrated a direct correlation. Limitations: CRP and albumin are not measured routinely and were ordered for a specific clinical reason leading to an indication bias. Also, no relationship with clinical outcome was established. Conclusions: NLR seems to be a good inflammatory biomarker in dialysis in addition to being easily available. However, controlled studies should be conducted to properly assess and validate NLR levels that would be clinically significant and relevant, as well as its prognostic significance and utility in a clinical setting.

  5. Assessment of neutrophil to lymphocyte ratio and mean platelet volume in pediatric familial Mediterranean fever patients

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    Ozge Basaran

    2017-01-01

    Full Text Available Background: Blood neutrophil to lymphocyte ratio (NLR and mean platelet volume (MPV both have been used as a simple marker of inflammation in many disorders. Here, we aimed to investigate the relationship between NLR, MPV, and familial Mediterranean fever (FMF. Materials and Methods: In this retrospective study, the files of FMF patients in pediatric rheumatology outpatient clinic were reviewed. There were 160 participants (68.4% in the FMF patient group and 74 participants (31.6% in the control group. Ninety of patients were in attack-free period, and 70 were in attack period. Results: The highest values of NLR were found in the patients at attack period. Patients in attack-free period and the participants in control group had similar levels of NLR (1.71 ± 0.83 and 1.91 ± 1.86 respectively (P = 0.457, and they had lower ratios than the patients did at attack period (4.10 ± 3.11 (P < 0.001 for both. There was no significant difference between MPV values of attack patients (8.35 ± 4.91 and attack-free patients (8.43 ± 1.15 (P = 0.074. MPV values of attack patients and attack-free patients were significantly higher than control group (7.99 ± 0.81 (P < 0.001 for both. Conclusion: NLR ratio may indicate FMF attack period. Since there was no significant difference between attack-free patients and control groups, NLR ratio cannot be used as a subclinical inflammation marker. However, NLR could be a useful predictor of inflammation in FMF patients. On the other hand, since our attack and attack-free patients have similar MPV values and both had greater MPV values than control group, we suggest that MPV may be used to show subclinical inflammation.

  6. The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

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    Cox, Samantha; Hurt, Christopher; Grenader, Tal; Mukherjee, Somnath; Bridgewater, John; Crosby, Thomas

    2017-10-01

    The derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. 258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). An elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479]. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Prognostic roles of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in ovarian cancer: a meta-analysis of retrospective studies.

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    Zhao, Zhe; Zhao, Xinrui; Lu, Jingjing; Xue, Jing; Liu, Peishu; Mao, Hongluan

    2018-04-01

    The systemic inflammatory response markers have been reported to be associated with the prognosis of various cancers. We conducted this meta-analysis of retrospective studies to evaluate and identify the prognostic impact of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on ovarian cancer. PubMed, EMBASE, and China National Knowledge Infrastructure databases were included to search for eligible studies. The following terms were used: "neutrophil to lymphocyte ratio", "NLR", "platelet to lymphocyte ratio", "PLR", "ovarian cancer", "ovary cancer", "ovarian carcinoma", "ovary carcinoma", "ovarian neoplasm", "ovary neoplasm", "ovarian tumor", and "ovary tumor". The random-effects model was chosen to estimate the pooled HR with 95% CI. Heterogeneity between studies was assessed by Higgins I 2 value. The stability and heterogeneity of studies were analyzed by sensitivity analysis. Publication bias was examined by Egger's test and Begg's test with the funnel plots. 13 studies consisting of 3467 patients were considered for meta-analysis. We found that the high NLR had a poor prognostic impact on OS and PFS in ovarian cancer, with a pooled HR 1.70, 95% CI 1.35-2.15 and HR 1.77, 95% CI 1.48-2.12, respectively. Similarly, the results showed the high PLR adversely affected OS and PFS in ovarian cancer, with a pooled HR 2.05, 95% CI 1.70-2.48 and HR 1.85, 95% CI 1.53-2.25, respectively. In conclusion, we found that both NLR and PLR had an unfavorable impact on PFS and OS of patients with ovarian cancer. Our meta-analysis supported that NLR/PLR could be effective prognostic predictors of ovarian cancer.

  8. Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: A meta-analysis.

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    Takenaka, Yukinori; Oya, Ryohei; Kitamiura, Takahiro; Ashida, Naoki; Shimizu, Kotaro; Takemura, Kazuya; Yamamoto, Yoshifumi; Uno, Atsuhiko

    2018-03-01

    Neutrophils play substantial roles in cancer progression. Previous reports demonstrated the prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in various types of solid cancers. The purpose of this study was to quantify the prognostic impact of NLR on head and neck squamous cell carcinoma (HNSCC). We systematically searched electronic databases, identified articles regarding NLR and HNSCC mortality, and extracted hazard ratios (HRs) and 95% confidence intervals (CIs). Pooled HRs for overall survival (OS) and disease-specific survival (DSS) were estimated using random effect models. Nineteen studies enrolling 3770 patients were included in the analyses. Overall, NLR greater than the cutoff value was associated with poorer OS and DSS (HR 1.69; 95% CI 1.47-1.93; P < .001 and HR 1.88; 95% CI 1.20-2.95; P = .006, respectively). Elevated NLR predicts worse outcomes in patients with HNSCC. © 2017 Wiley Periodicals, Inc.

  9. Influence of neutrophile granulocyte/lymphocyte ratio (NLR on poor prognosis of elderly AECOPD patients during hospital stay

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    Jian-Rong Cui

    2016-01-01

    Full Text Available Objective: To discuss the influence of neutrophile granulocyte/lymphocyte ratio(NLR to the poor prognosis of elderly AECOPD patients during the stay in hospital. Method: A total of 133 cases elderly patients with AECOPD admitted in our hospital from March 2013 to September 2014 were selected, and divided them into death group (31 cases and survival group (102 cases according to in-hospital death occurrence; To compare the on admission general clinical data, therapy method, lung function, blood routine examination [white blood cell count (WBC, neutrophile granulocyte/lymphocyte ratio(NLR], C-reactive protein (CRP, blood gas analysis and blood biochemical indexes in both groups, and drew ROC curve for a analysis of the clinical value of NLR in the prediction of death. Results: Among 133 cases of elderly AECOPD patients: the proportion of combined pulmonary heart disease and mechanical ventilation in death group was higher than that in survival group, PaCO2, WBC count, neutrophil count, NLR, CRP level in death group was higher, but lymphocyte count, serum albumin(ALB in death group was lower; multiple logistic regression analysis showed that NLR presented independent positive correlation with the in-hospital death in elderly AECOPD patients; ROC curve analysis showed that the ROCAUC of NLR to the inhospital death in elderly AECOPD patients was 0.787, the best diagnostic node value was 7.3, sensitivity and specificity were 77.4% and 74.5% respectively; bounded by NLR(7.3, divided patients into NLR≥7.3 group and NLR<7.3 group, hospital stays, CRP level and mortality in NLR≥7.3 group were higher than that in NLR<7.3 group. Conclusion: NLR was the high risk factor of the in-hospital death in elderly AECOPD patients, early detection of NLR level had a certain difference to the evaluation for short-term prognosis of elderly AECOPD patients and guide treatment.

  10. Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis

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    Xiao, Wei-Kai; Chen, Dong; Li, Shao-Qiang; Fu, Shun-Jun; Peng, Bao-Gang; Liang, Li-Jian

    2014-01-01

    Neutrophil-lymphocyte ratio (NLR) has recently been reported as a predictor of Hepatocellular carcinoma (HCC). However, its prognostic value in HCC still remains controversial. In this study, we aimed to evaluate the association between NLR and clinical outcome of HCC patients by performing meta-analysis. A comprehensive literature search for relevant studies published up to August 2013 was performed by using PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95% CIs) as effect measures. A total of 15 studies encompassing 3094 patients were included in this meta-analysis. Our pooled results showed that high NLR was associated with poor overall survival (OS) and disease free survival (DFS) in HCC initially treated by liver transplantation (HR = 3.42, 95% CI:2.41-4.85,P = 0.000; HR = 5.90, 95% CI:3.99-8.70,P = 0.000, respectively) and surgical resection (HR = 3.33, 95% CI:2.23-4.98, P = 0.000; HR = 2.10, 95% CI: 2.06–2.14, respectively). High NLR was also associated with poor OS in HCC treated by radiofrequency-ablation (HR = 1.28, 95%CI: 1.10-1.48, P = 0.000), TACE (HR = 2.52, 95% CI: 1.64-3.86, P = 0.000) and mixed treatment (HR = 1.85, 95% CI: 1.40-2.44, P = 0.000), respectively. In addition, high NLR was significantly correlated with the presence of vascular invasion (OR = 2.69, 95% CI: 2.01–3.59, P = 0.000), tumor multifocality (OR = 1.74, 95% CI: 1.30–2.34, P = 0.000) and higher incidence of AFP ≥ 400 ng/ml (OR = 1.46, 95% CI: 1.01–2.09, P = 0.04). Elevated NLR indicates a poor prognosis for patients with HCC. NLR may be a convenient, easily-obtained, low cost and reliable biomarker with prognostic potential for HCC

  11. Prognostic value of neutrophil to lymphocyte ratio in patients with acute pulmonary embolism: a restrospective study.

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    Kayrak, Mehmet; Erdoğan, Halil Ibrahim; Solak, Yalcin; Akilli, Hakan; Gül, Enes Elvin; Yildirim, Oğuzhan; Erer, Murat; Akilli, Nezire Belgin; Bekci, Taha Tahir; Aribaş, Alpay; Yazici, Mehmet

    2014-01-01

    Acute pulmonary embolism (PE) is a serious clinical condition characterised by a high mortality rate. Previous studies showed that leukocytosis was associated with recurrences of venous thromboemboli, major bleeding and increased mortality. The aim of the present study was to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR) in patients with acute PE during short term follow-up. A total of 640 patients were screened by I26 code of ICD-9 and 359 patients were included as cases of confirmed acute PE. Admission blood counts and clinical data were obtained from medical charts. The predictors of 30-day mortality were examined. Fifty-one out of 359 patients (14.2%) included in the study died during 30 days follow-up. In multivariate Cox regression analysis systolic blood pressure (HR:0.97 (0.94-0.99 CI95%), p=0.019), diabetes mellitus (HR:3.3 (1.30-8.39 CI95%), p=0.012), CK-MB(HR:1.03 (1.01-1.06 CI95%), p=0.024) and NLR (HR:1.03 (1.01-1.06 CI95%), p=0.008) were predictors of 30-day mortality. An optimal cut-off value of NLR was determined as 9.2 by using ROC curve. Hazards ratio of NLR>9.2 was found to be 3.60 (1.44-9.18 CI95%, p=0.006). NLR>9.2 had a sensitivity, specificity, negative predictive value, and positive predictive value of 68.6%, 80.5%, 93.9% and 36.5%, respectively. NLR on hospital admission may be a predictor of 30-day mortality in acute PE. Since complete blood count is a part of the routine laboratory investigation in the most hospitalised patients use and preliminary promising results of this study, NLR should be investigated in future prospective randomised trials regarding prognostic value in acute PE. Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  12. Is Preoperative Neutrophil Lymphocyte Ratio a Reliable Prognostic Parameter for Localized Prostate Cancer?

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    Tümay İpekçi

    2017-12-01

    Full Text Available Objective: In spite of all efforts, prostate cancer is still the 2nd highest cause of cancer-related deaths in men. For this reason new developments are needed in diagnosis, treatment and follow-up of prostate cancer. Neutrophil/lymphocyte (N/L ratio is a cheap and effective parameter used for research into many solid tumors; but there are not enough studies on the reliability of this parameter in prostate cancer. In this study we researched the efficacy of N/L ratio in localized prostate cancer. Materials and Methods: Between March 9, 2012 and April 23, 2017, the data of 140 patients who underwent radical prostatectomy with localized prostate cancer were screened retrospectively. The patients’ ages, preoperative prostate specific antigen (PSA and N/L ratio, pathologic stage, pathologic Gleason score, tumor volume, lymph node involvement, surgical margin positivity and presence or absence of 3rd month biochemical recurrence were noted. The correlations between N/L ratio with age, PSA, pathologic parameters, surgical margin positivity and biochemical recurrence were investigated. Results: The mean age of patients was 63.0±5.9 years, mean PSA value was 10.8±8.5 ng/mL and mean N/L ratio was 2.5±1.9. There was no correlation found between N/L ratio and PSA, pathologic stage, Gleason score, lymph node involvement, tumor volume, surgical margin positivity and biochemical recurrence (p>0.05. Conclusion: In our study investigating 140 patients with localized prostate cancer, we did not identify any correlation between N/L ratio and PSA, surgical stage and Gleason score, surgical margin positivity, and 3rd month biochemical recurrence. When the literature is investigated, it appears that N/L ratio is effective for metastatic prostate cancer. To provide a more accurate judgment of the role of N/L ratio in localized prostate cancer, there is a need for new studies with broader patient series.

  13. Prognostic meaning of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ration (LMR) in newly diagnosed Hodgkin lymphoma patients treated upfront with a PET-2 based strategy.

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    Romano, Alessandra; Parrinello, Nunziatina Laura; Vetro, Calogero; Chiarenza, Annalisa; Cerchione, Claudio; Ippolito, Massimo; Palumbo, Giuseppe Alberto; Di Raimondo, Francesco

    2018-06-01

    Recent reports identify NLR (the ratio between absolute neutrophils counts, ANC, and absolute lymphocyte count, ALC), as predictor of progression-free survival (PFS) and overall survival (OS) in cancer patients. We retrospectively tested NLR and LMR (the ratio between absolute lymphocyte and monocyte counts) in newly diagnosed Hodgkin lymphoma (HL) patients treated upfront with a PET-2 risk-adapted strategy. NLR and LMR were calculated using records obtained from the complete blood count (CBC) from 180 newly diagnosed HL patients. PFS was evaluated accordingly to Kaplan-Meier method. Higher NLR was associated to advanced stage, increased absolute counts of neutrophils and reduced count of lymphocytes, and markers of systemic inflammation. After a median follow-up of 68 months, PFS at 60 months was 86.6% versus 70.1%, respectively, in patients with NLR ≥ 6 or NLR PET-2 scan (p PET-2 was an independent predictor of PFS in multivariate analysis. Advanced-stage patients (N = 119) were treated according to a PET-2 risk-adapted protocol, with an early switch to BEACOPP regimen in case of PET-2 positivity. Despite this strategy, patients with positive PET-2 still had an inferior outcome, with PFS at 60 months of 84.7% versus 40.1% (negative and positive PET-2 patients, respectively, p PET-2 status and to a lesser extend NLR in advanced stage, while LMR maintained its significance in early stage. By focusing on PET-2 negative patients, we found that patients with NLR ≥ 6.0 or LMR PET-2 scan, NLR and LMR can result in a meaningful prognostic system that needs to be further validated in prospective series including patients treated upfront with PET-2 adapted-risk therapy.

  14. The Predictive Value of Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio for the Effusion Viscosity in Otitis Media With Chronic Effusion.

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    Elbistanli, Mustafa Suphi; Koçak, Hasan Emre; Acipayam, Harun; Yiğider, Ayşe Pelin; Keskin, Mehmet; Kayhan, Fatma Tülin

    2017-05-01

    The objective of the authors' study was to investigate the predictive value of the neutrophil-lymphocyte rate (NLR) and platelet-lymphocyte rate (PLR) in otitis media with effusion and the correlation of the effusion type with these ratios. Retrospective case-control study. One hundred twenty-six pediatric patients diagnosed otitis media with chronic effusion and had ventilation tube inserted between October 2015 and July 2016 were included in the study group and 124 healthy children, who applied for the routine examination and had blood count analysis, were included in the control group. The patients in the study group were divided into 2 groups regarding the effusion viscosity, which was obtained from the patients' operation files. Seventy-one patients were included in the serous group and 55 patients in the mucous group. The NLR and PLR rates of the groups were compared and statistically evaluated. The average NLR and PLR rates were significantly higher in the study group than in the control group (P = 0.000, P = 0.004 respectively). Comparison of the serous and mucous groups with the control group revealed a significant difference between the control group and the serous group regarding the NLR and PLR (P = 0.000; P = 0.000 respectively), but not between the control group and mucous group (P = 0.694; P = 0.691 respectively). Neutrophil-lymphocyte rate and PLR had a predictive value for otitis media with effusion and additionally it was a laboratory indicator supporting the typing of the viscosity of the fluid accumulated in the middle ear.

  15. Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model.

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    Chrom, Pawel; Stec, Rafal; Bodnar, Lubomir; Szczylik, Cezary

    2018-01-01

    The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy. This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R 2 , Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups. Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R 2 , 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R 2 , 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups). Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.

  16. The relative role of neutrophils and platelets in the local accumulation of circulating lymphocytes at sites of ionophore A23187 inoculation

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    Hayes, J.M.; Simmons, R.L. (Univ. of Pittsburgh, PA (USA))

    1991-03-01

    The early cellular infiltrate at inflammatory sites consists predominantly of neutrophils and cells of the monocyte/macrophage lineage. The mechanism by which circulating, unsensitized lymphocytes accumulate at sites of inflammation is unknown. The pattern of accumulation of 111indium-labeled circulating thymocytes in response to local injections of the ionophore A23187 was studied and compared with the pattern of (125)iodinated albumin accumulation as a measure of vascular permeability. The kinetics of thymocyte accumulation differed from those of vascular permeability. Sublethal total-body irradiation (750 rads) markedly decreased thymocyte accumulation but had little effect on vascular permeability. Irradiation of the local site alone had no effect. T lymphocyte, T lymphoblast, and platelet accumulation generally followed the same pattern as thymocytes. Intravenous injection of neutrophils, but not platelets, partially restored lymphocyte accumulation in vivo in irradiated mice via a pathway involving the circulating neutrophil, and seemed to be independent of changes in vascular permeability.

  17. Mean Platelet Volume and Neutrophil-to-Lymphocyte Ratio in Patients with Crimean–Congo Hemorrhagic Fever

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    Derya Koçer

    2015-01-01

    Full Text Available Objectives: Crimean–Congo hemorrhagic fever (CCHF is a tick-borne zoonotic infection caused by Crimean Congo hemorrhagic fever virus (CCHFV. The aim of the present study was to investigate the association between blood neutrophil-to-lymphocyte ratio (NLR and mean platelet volume (MPV which are simple markers of subclinical inflammation and CCHF. We also investigated the relationship of these markers with coagulation parameters.Methods: Thirty-one suspected CCHF patients, who submitted to Training and Research Hospital, Kayseri, Turkey between 2009 and 2013, were evaluated retrospectively. Among thirty-one patients, nineteen were laboratory confirmed CCHF patients diagnosed by RT-PCR or CCHFV-specific IgM positivity. Alanine aminotransferase (ALT, aspartate aminotransferase (AST, lactate dehydrogenase (LDH, creatinin phosphokinase (CK, coagulation parameters, white blood cell counts (WBCs, and platelet counts of patient group were compared with twenty-five healthy individuals.Results: MPV, AST, ALT, LDH, CK and coagulation parameters were significantly higher in patients with CCHF than the controls, whereas WBCs, neutrophil, lymphocyte, hemoglobin, platelet counts and NLR were significantly lower (p<0.05. We found no significant correlation between MPV, NLR and coagulation parameters.Conclusions: Our study demonstrates that MPV and NLR may be beneficial markers in the diagnosis of CCHF. But these parameters should not be considered stand-alone tests for this use owing to nonspecificity with other diseases.

  18. Evaluation of blood neutrophil-lymphocyte ratio and platelet distribution width as inflammatory markers in patients with fibromyalgia.

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    Aktürk, Semra; Büyükavcı, Raikan

    2017-08-01

    Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and systemic symptoms. The aetiology and pathogenesis of fibromyalgia are not yet fully understood. Blood neutrophil/lymphocyte ratio (NLR) is a marker of systemic inflammatory response. Platelet distribution width (PDW) and mean platelet volume (MPV) are the determinants of platelet activation and studied as markers in inflammatory diseases. The aim of the present study was to evaluate levels of NLR,PDW and MPV in patients with fibromyalgia. A total of 197 FMS patients and 53 healthy controls are included in the study. Demographic characteristics, erythrocyte sedimentation rate, C-reactive protein, neutrophil, lymphocyte and platelet counts, platelet distribution width and mean platelet volume levels were recorded. In the patient group, the blood NLR and MPV were significantly higher and the PDW was significantly lower compared to the control group. In the roc curve analysis, blood PDW ≥had 90.4% sensitivity and 90% specificity in predicting fibromyalgia. The results of this study suggest NLR and PDW as promising inflammatory markers indicating fibromyalgia and may be beneficial in facilitating the diagnosis of FMS patients.

  19. The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

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    Tang, Xingxing; Du, Peng; Yang, Yong

    2017-10-01

    The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

  20. Neutrophil-to-lymphocyte ratio in predicting prognosis and course of community community-acquired pneumonia in hospitalized patients.

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    T. O. Pertseva

    2018-04-01

    Full Text Available Currently, a marker which could be used both to assess the severity of community acquired pneumonia (CAP and determine the risk of complications is being searched. According to some authors, Neutrophil-to-Lymphocyte Ratio (NLR could be such a marker. Therefore, the aim of our research was to determine the diagnostic significance of NLR in patients with CAP and to establish the relationship of NLR with other clinical and laboratory parameters. We conducted a retrospective analysis of 171 case histories of patients with CAP of 3 and 4 clinical groups, with the calculation of NLR (according to the common blood count. In the course of the work, it was found that NLR reflects a balance between the response of neutrophils and lymphocytes and this parameter is associated with the severity of systemic inflammation in patients with CAP. NLR has good diagnostic value in determining the mortality risk in patients with CAP, specially an increase in the level of NLR (more than 10 is associated with a high risk of life-threatening complications.

  1. Neutrophil-to-Lymphocyte Ratio as a Marker in Patients with Non-arteritic Anterior Ischemic Optic Neuropathy

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    Onur Polat

    2015-12-01

    Full Text Available Background: Non-arteritic anterior ischemic optic neuropathy (NAION is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Although the precise cause of NAION remains elusive, the etiology of NAION is believed to be multifactorial. Aims: To evaluate the utility of neutrophil-to-lymphocyte ratio (NLR as a simple and readily available prognostic factor for clinical disease activity in patients with NAION. Study Design: Case-control study. Methods: Forty-five patients with the diagnosis of NAION and 50 age- and sex-matched controls with/without any systemic or ocular diseases except cataract were retrospectively enrolled in the study. Demographic characteristics and laboratory findings including complete blood count of all patients and control subjects were obtained from the electronic medical record. The neutrophil and lymphocyte counts were recorded and the NLR was calculated. Results: White blood cell, neutrophil, NLR and platelet values of the NAION patients were significantly higher than those of the controls (p<0.001, p<0.001, p=0.004, p=0.037, respectively. Initial NLR values were negatively correlated with initial and the third month best corrected visual acuity levels in the study group. The optimum NLR cut-off point for NAION was 1.94. Conclusion: NLR could be considered as a new inflammatory marker for assessment of the severity of inflammation in NAION patients with its quick, cheap, easily measurable property with routine complete blood count analysis.

  2. [Immunologic indexes, enzyme status of lymphocytes and functional activity of blood neutrophils in children with infectious mononucleosis caused by Epstein-Barr virus].

    Science.gov (United States)

    Kurtasova, L M; Tolstikova, A E; Savchenko, A A

    2013-01-01

    Explore the immunological parameters, levels of activity of NAD(P)-dependent dehydrogenases lymphocytes, interferon status parameters, phagocytic activity and chemiluminescence response of neutrophils in the blood of children in the acute phase of infectious mononucleosis caused by the Epstein-Barr virus. 65 children at the age of 4-6 years old with infectious mononucleosis caused by EBV in acute phase were observed. Such indexes as cell-mediated, humoral and interferon immunity, NAD(P)-depended dehydrogenases activity in blood lymphocyte, phagocytes activity, levels of spontaneous and induced chemiluminescence ofperipheral blood neutrophils were studied. Children with EVB-infection have immunophenotype spectrum changes and changes of enzymes status of blood lymphocytes against the increasing in leucocytes and the useful increasing in lymphocytes. The useful increasing in IgA, IgM, IgG contenting in serum blood were found. The decreasing of spontaneous production of IFN alpha and the decreasing of induced production of IFNalpha, IFNgamma were determined. The breach of phagocytes activity and chemiluminescent response of blood neutrophils were found. The children in the acute phase of infectious mononucleosis caused by the Epstein-Barr virus, there are changes in the immune status, changes the activity of NAD(P)-dependent dehydrogenases in blood lymphocytes, marked changes in functional and metabolic state of peripheral blood neutrophils.

  3. Combination of neutrophil lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma

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    Feng JF

    2013-11-01

    Full Text Available Ji-Feng Feng,1 Ying Huang,2 Jin-Shi Liu1 1Department of Thoracic Surgery, 2Department of Operating Theatre, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China Background: Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various types of cancers. This study investigated the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR, collectively named the CNP, for predicting survival in patients with esophageal squamous cell carcinoma (ESCC. Materials and methods: The CNP was calculated on the basis of data obtained on the day of admission: patients with both elevated NLR (>3.45 and PLR (>166.5 were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. Results: The CNP was associated with tumor length (P<0.001, differentiation (P=0.021, depth of invasion (P<0.001, and nodal metastasis (P<0.001. No significant differences were found between the CNP and morbidity. However, significant differences were found between the CNP and mortality (P<0.001. The overall survival in the CNP 0, CNP 1, and CNP 2 groups were 63.4%, 50.0%, and 20.2%, respectively (CNP 0 versus CNP 1, P=0.014; CNP 1 versus CNP 2, P<0.001. Multivariate analyses showed that CNP was a significant predictor of overall survival. CNP 1–2 had a hazard ratio (HR of 1.964 (95% confidence interval [CI]: 1.371–2.814, P<0.001 for overall survival. CNP (HR =1.964, P<0.001 is superior to NLR (HR =1.310, P=0.053 or PLR (HR =1.751, P<0.001 as a predictive factor. Conclusion: The CNP is considered a useful predictor of postoperative survival in patients with ESCC. The CNP is superior to NLR or PLR as a predictive factor in patients with ESCC. Keywords: esophageal squamous cell carcinoma (ESCC, neutrophil lymphocyte ratio (NLR, platelet lymphocyte ratio (PLR, overall survival

  4. The ratio Neutrophil/Lymphocyte and Platelet/Lymphocyte in patient with Rheumatoid Arthritis that are Treating with Anti-TNF

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    İsmail Boyraz

    2014-06-01

    Full Text Available OBJECTIVES: Rheumatoid arthritis (RA is a chronic inflammatory disorder with unknown etiology. RA is characterized by a variable course of remissions and relapses, and subclinical inflammation persists between the disease exacerbations. Anti-TNF therapies have become more often preferred in recent years in the treatment of RA. The aim of the present study was to determine the relationship between N/L and P/L ratios and subclinical inflammation in patients with RA who achieved remission with anti-TNF therapy. METHODS: The present study was a retrospective, controlled and multicenter study. The present study reviewed the medical records of the patients who were on follow-up in the outpatient clinics of the Department of Physical Therapy in Abant İzzet Baysal University and Harran University due to rheumatoid arthritis (RA and who achieved remission with anti-TNF therapy.A total of 80 patients in the inactive phase of RA and 45 healthy subjects in the control group were included in the study. Hemogram results of the people were examined retrospectively. RESULTS: There was significant difference between the patient and the control group in terms of platelet ratio and lymphocyte and neutrophil ratio. There was no significant difference between the group in terms of N/L and P/L ratios.CONCLUSIONS:  In the current study, we found significant differences between the patient and the control group in terms of neutrophil, lymphocyte, and platelet counts; however, there was no significant difference between the two groups in terms of N/L and P/L ratios. These findings suggest that therapies with anti-TNF agents in patients with RA achieved complete control of inflammation. 

  5. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in acute pulmonary embolism: a systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Qian; Ma, Junfen; Jiang, Zhiyun; Ming, Liang

    2018-02-01

    Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to predict prognosis of acute pulmonary embolism (PE). However, the prognostic value of NLR and PLR remained inconsistent between studies. The aim of this meta-analysis was to assess the prognostic role of NLR and PLR in acute PE. We systematically searched Pubmed, Embase, Web of Science and CNKI for relative literature up to March 2017. The pooled statistics for all outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). The statistical analyses were performed using Review Manager 5.3.5 analysis software and Stata software. Totally 7 eligible studies consisting of 2323 patients were enrolled in our meta-analysis. Elevated NLR was significantly associated with overall (short-term and long-term) mortality (OR 10.13, 95% CI 6.57-15.64, Panalysis revealed that NLR and PLR are promising biomarkers in predicting prognosis in acute PE patients. We suggest NLR and PLR be used routinely in the PE prognostic assessment.

  6. The relationship between neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with obstructive sleep apnea syndrome

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    Hülya Günbatar

    2015-09-01

    Full Text Available Objective: There is a strong relationship between obstructive sleep apnea syndrome (OSAS and cardiovascular disease (CVD. Chronic intermittent hypoxia, inflammation, oxidative stress, and endothelial dysfunction may create etiologic mechanisms, connection between OSAS to CVD. Inflammation play an important role in the development of CVD. Platelet- Lymphocyte Ratio (PLR and Neutrophil-lymphocyte Ratio (NLR are new biomarkers showing inflammation. This study was designed to investigate the association between PLR, NLR and relationship between severity of OSAS, polysomnographic parameters and PLR. Methods: This was a cohort study in which patients who had undergone a full night polysomnography for diagnosis of OSA were recruited. Patients were divided according to their apnea hypopnea index (AHI scores into OSAS negative simple snoring (Group 1; AHI 30 groups. Results: A total of 111 patients were included in this study. There were 26, 22 and 63 patients in Groups 1, 2 and 3, respectively. PLR were significantly different between groups (Group 1: 87.12, Group 2: 103.6, Group 3: 112.5, p < 0.05. PLR were significantly correlated with NLR, AHI, oxygen desaturation index, average and minimum O2 saturation values (p < 0.05. Multiple regression analysis demonstrated that PLR is an independent predictor of CVD. PLR cut-off value for demonstrating the presence of CVD is higher than 86.03. Conclusion: In the light of these findings, PLR is strongly associated with the severity of OSAS. PLR might be used as a biomarker to predict CVD in OSAS patients.

  7. Are neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as effective as Fournier's gangrene severity index for predicting the number of debridements in Fourner's gangrene?

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    Kahramanca, Sahin; Kaya, Oskay; Özgehan, Gülay; Irem, Burak; Dural, Ibrahim; Küçükpınar, Tevfik; Kargıcı, Hülagü

    2014-03-01

    Fournier's gangrene (FG) is a rapidly progressive and necrotizing infection of the subcutaneous and fascial tissues with a high mortality rate. In the present study, we aimed to investigate prognostic factors and analyze the outcomes of 68 patients in a tertiary reference hospital. Patients admitted to the emergency department were investigated retrospectively between January 2006 and January 2013 and divided into two groups. The patients in Group I (G1) required one debridement, and Group II (G2) patients required more than one. Patient demographic and clinical characteristics were encoded. Fournier's Gangrene Severity Index (FGSI) scores, neutrophil-lymphocyte ratios (NLR), and platelet-lymphocyte ratios (PLR) were calculated. Prognostic factors were compared between the groups. There were no statistically significant differences between the groups in terms of mean age, female-male ratio, or duration of symptoms on admission; however, there were more infection sources, predisposal factors, and positive culture results in G2. Additionally, hospital stay, total cost, and mortality rate values were high in G2. We found statistically higher NLR and PLR ratios in G2, but there was no significant difference in FGSI scores between the groups. The FGSI scoring system was not found to be valuable in determining prognosis. However, NLR and PLR were valuable, and previous use of NLR and PLR for determining Fournier's gangrene prognosis could not be found in the English literature.

  8. Can Serum Neutrophil-to-Lymphocyte Ratio Be a Predictive Biomarker to Help Differentiate Active Chronic Otitis Media From Inactive Chronic Otitis Media?

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    Tansuker, Hasan Deniz; Eroğlu, Sinan; Yenigün, Alper; Taşkin, Ümit; Oktay, Mehmet Faruk

    2017-05-01

    The authors' aim was to investigate whether serum neutrophil to lymphocyte ratio might be used as a predictive biomarker to help differentiate active from inactive chronic otitis media (COM). Two hundred fifty-nine patients having inactive COM received tympanoplasty without mastoidectomy and were identified as Group 1. On the other hand, 254 patients having active COM received tympanoplasty with mastoidectomy and were identified as Group 2. Routine hemogram tests were performed preoperatively for both the groups. By performing a chart review, white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet, and mean platelet volume values were compared between the groups in an age-matched and sex-matched manner. A total of 513 COM patients with age range of 7 to 65 years were included in the study. Two hundred seventy-five patients (53.6%) were male, 238 were (46.4%) female. Preoperatively both serum neutrophil and lymphocyte counts were significantly higher in Group 2 (P = 0.015 and P = 0.004, respectively). However, the neutrophil-to-lymphocyte ratios between the groups were not significantly different (P = 0.511). No statistically significant differences were identified from preoperative neutrophil-to-lymphocyte ratios between patients having active COM and inactive COM. Level NA.

  9. Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

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    Chen L

    2017-05-01

    Full Text Available Li Chen,1 Yanjiao Zuo,1 Lihua Zhu,2 Yuxin Zhang,3 Sen Li,1 Fei Ma,4 Yu Han,5 Hongjiang Song,1 Yingwei Xue11Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, 3Department of General Surgery, Mudanjiang First People’s Hospital, Mudanjiang, 4Department of Breast Surgery, 5Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaBackground: Accurate and useful predictors of gastric carcinoma treated with neoadjuvant chemotherapy are lacking at present. We aim to explore the potential prognostic significance of the neutrophil-to-lymphocyte ratio (NLR in advanced gastric cancer receiving S-1 plus oxaliplatin (SOX or oxaliplatin and capecitabine (XELOX regimen.Methods: We enrolled 91 patients with advanced gastric cancer treated with neoadjuvant chemotherapy from August 2008 to September 2015. The peripheral venous blood samples were collected before neoadjuvant chemotherapy. The NLR was divided into two groups: low NLR <2.17 group and high NLR ≥2.17 group. Univariate analysis on disease-free survival (DFS and overall survival (OS were generated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were assessed by univariate analyses, and the independent prognostic factors were evaluated using multivariate analysis (Cox’s proportional-hazards regression model.Results: The univariate analysis showed that median DFS and median OS were worse for high NLR values than low NLR values before neoadjuvant chemotherapy (median DFS: 19.97 and 26.87 months, respectively, P=0.299; median OS: 25.83 and 29.73 months, respectively, P=0.405. Multivariate analysis showed that the NLR before neoadjuvant

  10. The Combination of Platelet Count and Neutrophil Lymphocyte Ratio Is a Predictive Factor in Patients with Esophageal Squamous Cell Carcinoma

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    Ji-Feng Feng

    2014-10-01

    Full Text Available OBJECTIVE: The prognostic value of inflammation indexes in esophageal cancer was not established. In this study, therefore, both prognostic values of Glasgow prognostic score (GPS and combination of platelet count and neutrophil lymphocyte ratio (COP-NLR in patients with esophageal squamous cell carcinoma (ESCC were investigated and compared. METHODS: This retrospective study included 375 patients who underwent esophagectomy for ESCC. The cancer-specific survival (CSS was calculated by the Kaplan-Meier method, and the difference was assessed by the log-rank test. The GPS was calculated as follows: patients with elevated C-reactive protein (>10 mg/l and hypoalbuminemia (300 × 109/l and neutrophil lymphocyte ratio (>3 were assigned to COP-NLR2. Patients with one or no abnormal value were assigned to COP-NLR1 or COP-NLR0, respectively. RESULTS: The 5-year CSS in patients with GPS0, 1, and 2 was 50.0%, 27.0%, and 12.5%, respectively (P < .001. The 5-year CSS in patients with COP-NLR0, 1, and 2 was 51.8%, 27.0%, and 11.6%, respectively (P < .001. Multivariate analysis showed that both GPS (P = .003 and COP-NLR (P = .003 were significant predictors in such patients. In addition, our study demonstrated a similar hazard ratio (HR between COP-NLR and GPS (HR = 1.394 vs HR = 1.367. CONCLUSIONS: COP-NLR is an independent predictive factor in patients with ESCC. We conclude that COP-NLR predicts survival in ESCC similar to GPS.

  11. The combination of platelet count and neutrophil lymphocyte ratio is a predictive factor in patients with esophageal squamous cell carcinoma.

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    Feng, Ji-Feng; Huang, Ying; Chen, Qi-Xun

    2014-10-01

    The prognostic value of inflammation indexes in esophageal cancer was not established. In this study, therefore, both prognostic values of Glasgow prognostic score (GPS) and combination of platelet count and neutrophil lymphocyte ratio (COP-NLR) in patients with esophageal squamous cell carcinoma (ESCC) were investigated and compared. This retrospective study included 375 patients who underwent esophagectomy for ESCC. The cancer-specific survival (CSS) was calculated by the Kaplan-Meier method, and the difference was assessed by the log-rank test. The GPS was calculated as follows: patients with elevated C-reactive protein (> 10 mg/l) and hypoalbuminemia (l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0, respectively. The COP-NLR was calculated as follows: patients with elevated platelet count (> 300 × 10(9)/l) and neutrophil lymphocyte ratio (> 3) were assigned to COP-NLR2. Patients with one or no abnormal value were assigned to COP-NLR1 or COP-NLR0, respectively. The 5-year CSS in patients with GPS0, 1, and 2 was 50.0%, 27.0%, and 12.5%, respectively (P GPS (P = .003) and COP-NLR (P = .003) were significant predictors in such patients. In addition, our study demonstrated a similar hazard ratio (HR) between COP-NLR and GPS (HR = 1.394 vs HR = 1.367). COP-NLR is an independent predictive factor in patients with ESCC. We conclude that COP-NLR predicts survival in ESCC similar to GPS.

  12. Neutrophil-to-lymphocyte ratio as a novel-potential marker for predicting prognosis of Bell palsy.

    Science.gov (United States)

    Bucak, Abdulkadir; Ulu, Sahin; Oruc, Serdar; Yucedag, Fatih; Tekin, Mustafa Said; Karakaya, Fatıma; Aycicek, Abdullah

    2014-07-01

    Bell palsy can be defined as an idiopathic, acute, facial nerve palsy. Although the pathogenesis of Bell palsy is not fully understood, inflammation seems to play important role. Neutrophil-to-lymphocyte (NLR) ratio was defined as a novel potential marker to determine inflammation and it is routinely measured in peripheral blood. Our goal was to investigate the relationship between Bell palsy and inflammation by using NLR. Retrospective study. The 54 patients who were followed up for Bell palsy for a period of 1 to 3 years, along with 45 age- and sex-matched controls, were included in the study. An automated blood cell counter was used for NLR measurements. All patients were treated with prednisone, 1 mg/kg per day with a progressive dose reduction. Patients were classified according to the House-Brackmann grading system at posttreatment period. Those with House-Brackmann grade I and grade II were regarded as satisfactory recovery; and those with House-Brackmann grade III to grade VI were regarded as nonsatisfactory recovery. The mean NLR and neutrophil values in patients with Bell palsy were significantly higher than in the control group (P=0.001 and PBell palsy and its prognosis. Our result suggest that while evaluating Bell palsy patients, NLR might be taken into account as a novel potential marker to predict the patients' prognosis. 3b. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Comparison of absolute neutrophil to CD4 lymphocyte values as a ...

    African Journals Online (AJOL)

    1.5 x 109/L is therefore obviously not appropriate for people of negroid descent whose lower reference limit is ANC 1.3 x 109/L.6,7 Neutropenia remains the most common predisposing factor to infections in cancer pa- tients.1,8,9 The accepted definition of neutropenia is an absolute neutrophil count ≤ 1.5 x 109/L,8 though ...

  14. Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Suciu, Stefan; Punt, Cornelis J A

    2007-01-01

    : A total of 363 patients were randomly assigned and baseline blood neutrophil and leukocyte counts were available from 316 and 350 patients, respectively. A high neutrophil count (> 7.5 x 10(9)/L) was an independent prognostic factor for short overall survival (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P...... = 0.02), and a high leukocyte count (> 10 x 10(9)/L) was an independent prognostic factor of both short overall survival (HR, 1.7; 95% CI, 1.3 to 2.4; P = 0.0005) and short progression-free survival (HR, 1.5; 95% CI, 1.1 to 2.1; P = 0.008). CONCLUSION: A high pretreatment count of neutrophils in blood...

  15. The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients

    Directory of Open Access Journals (Sweden)

    Matteo Piciucchi

    2017-03-01

    Full Text Available Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR, the Odonera Prognostic Nutritional Index (PNI, the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis. In a single center cohort study, inflammatory-based scores were assessed at diagnosis and their prognostic relevance as well as that of clinic-pathological variables were evaluated through multiple logistic regression and survival probability analysis. In 206 patients, age, male sex, tumor size, presence of distant metastasis, access to chemotherapy, and an NLR > 5 but not other scores were associated with overall survival (OS at multivariate analysis. Patients with an NLR < 5 had a median survival of 12 months compared to 4 months in those with an NLR > 5. In the 81 patients with distant metastasis at diagnosis, an NLR > 5 resulted in the only variable significantly associated with survival. Among patients with metastatic disease who received chemotherapy, the median survival was 3 months in patients with an NLR > 5 and 7 months in those with an NLR < 5. The NLR might drive therapeutic options in PDAC patients, especially in the setting of metastatic disease.

  16. Evaluation of the prognostic value of neutrophil to lymphocyte ratio in patients with hypertriglyceridemia-induced acute pancreatitis.

    Science.gov (United States)

    Wang, Yuchen; Fuentes, Harry E; Attar, Bashar M; Jaiswal, Palash; Demetria, Melchor

    Recent studies attribute promising prognostic values to various inflammatory biomarkers in acute pancreatitis, including the following: the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red cell distribution width (RDW). We aimed to determine the performance of these biomarkers for detecting disease severity in patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP). We retrospectively reviewed 110 patients with HTG-AP and compared the NLR, PLR, and RDW in different severity groups. We performed receiver-operating characteristic (ROC) analysis to identify the optimal cut-off value for NLR to predict severe AP. NLR was significantly higher in patients with severe AP than mild and moderately severe AP (14.6 vs. 6.9, p analysis (Odds ratio 6.71, p = 0.019). NLR represents an inexpensive, readily available test with a promising value to predict disease severity in HTG-AP. Among the three inflammatory biomarkers, NLR has the highest discriminatory capacity for severe HTG-AP, with an optimal cut-off value of 10. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  17. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Novel Markers for Diagnosis of Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Mohammad Amin Bahrami

    2016-04-01

    Full Text Available Background: Sudden sensorineural hearing loss (SSNHL is a common otologic disease characterized by a loss of hearing greater than 30 dB in three consecutive frequen­cies which occurs in less than 72 hours. Objective: To investigate the role of neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR on sudden sensorineural hearing loss (SSNHL. Search strategy: A PubMed, Science Direct, Scopus, OVID, EMBASE and Google Scholar search (date last searched April 2016 without any time, language and location restriction was done. Inclusion criteria: All case-control studies, which have been investigated the relationship of NLR and PLR with the occurrence of SSNHL were included in our meta-analysis. Results: A total of 5 case-control studies were included in the study. All 5 studies have been reported NLR of patients and control groups (611 patients and 804 controls. Our analysis showed that the mean NLR of patients is 1.12 (0.82-1.43 unit higher than that of controls with 95% CI which is statistically significant. Also, 3 studies have been reported PLR of patients and control groups (512 patients and 705 controls. Our analysis showed that the mean PLR of patients is 0.57 (0.08-1.05 unit higher than that of controls with 95% CI which is statistically significant too. Conclusions: This meta-analysis confirmed the relationship of NLR and PLR with SSNHL. Therefore, these parameters can be considered as new markers in diagnosis of SSNHL. 

  18. Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios Are More Effective than the Fournier's Gangrene Severity Index for Predicting Poor Prognosis in Fournier's Gangrene.

    Science.gov (United States)

    Yim, Sang Un; Kim, Sun Woo; Ahn, Ji Hoon; Cho, Yang Hyun; Chung, Hoseok; Hwang, Eu Chang; Yu, Ho Song; Oh, Kyung Jin; Kim, Sun-Ouck; Jung, Seung Il; Kang, Taek Won; Kwon, Dong Deuk; Park, Kwangsung

    2016-04-01

    We investigated the value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as markers of mortality in patients with Fournier's gangrene. Records from 62 patients treated for Fournier's gangrene between 2003 and 2014 were reviewed retrospectively. Data were collected regarding medical history, symptoms, physical examination findings, admission laboratory tests, and the extent of body surface area involved (%). Fournier's Gangrene Severity Index score, NLR, and PLR were calculated. The data were assessed separately for surviving and deceased patients. Of the 62 patients, 36 survived (58%, group 1) and 26 died (42%, group 2). Parameters that were statistically different between the two groups (p Fournier's Gangrene Severity Index score, and admission laboratory parameters, including body temperature, heart rate, bicarbonate, albumin, and serum calcium. The average body surface area affected in group 2 was statistically different from that of group 1 (6.0% versus 2.3%, p = 0.001). A high Fournier's Gangrene Severity Index score (>9), high NLR (>8), and high PLR (>140) were associated more frequently with group 2 patients. Multivariable regression analysis showed that high NLR (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.25-17.3; p = 0.022) and high PLR (adjusted OR, 11.6; 95% CI, 2.7-49.5; p = 0.001) were independent prognostic factors for poor prognosis from Fournier's gangrene. However, the Fournier's Gangrene Severity Index score did not shown any statistically significant effect on mortality (p = 0.086). The Fournier's Gangrene Severity Index scoring system was not associated with determining poor prognosis, however, high NLR and high PLR were associated with predictors of mortality in patients with Fournier's gangrene.

  19. Strong Prognostic Value of Tumor-infiltrating Neutrophils and Lymphocytes Assessed by Automated Digital Image Analysis in Early Stage Cervical Cancer

    DEFF Research Database (Denmark)

    Carus, Andreas; Donskov, Frede; Switten Nielsen, Patricia

    2014-01-01

    INTRODUCTION Manual observer-assisted stereological (OAS) assessments of tumor-infiltrating neutrophils and lymphocytes are prognostic, accurate, but cumbersome. We assessed the applicability of automated digital image analysis (DIA). METHODS Visiomorph software was used to obtain DIA densities...... with the prognostically strongest manual OAS assessments in the peritumoral compartment. In multivariate analysis, CD66b and CD8 densities, assessed by DIA, and regional lymph node metastases were independent predictors of RFS, while CD163 density and FIGO stage were not. The CD66b/CD8 tumorassociated neutrophil...

  20. Expresión de L-selectina en linfocitos T y neutrófilos de niños infectados con HIV L-selectin expression on T lymphocytes and neutrophils in HIV infected children

    Directory of Open Access Journals (Sweden)

    Gaddi Eduardo

    2005-04-01

    Full Text Available La capacidad de los leucocitos de abandonar la circulación y migrar hacia los tejidos es un paso crítico de la respuesta inmune. La L-selectina, selectina leucocitaria (CD62L, media la unión de linfocitos a las vénulas endoteliales altas de los ganglios linfáticos periféricos, y también participa en la adhesión de linfocitos, neutrófilos y monocitos al endotelio vascular activado en los sitios de inflamación. En este trabajo se estudiaron los niveles de expresión de L-selectina sobre los linfocitos T y polimorfonucleares neutrófilos en 25 niños HIV(+ sin tratamiento antirretroviral y 25 niños sanos HIV(-, evaluando además su comportamiento en 10 de los pacientes, luego de 6 meses de iniciada la terapéutica específica para el HIV. El número de linfocitos TCD3+, CD4+ y CD8+ que expresan CD62L se encontró significativamente disminuido en los niños HIV(+ con respecto al grupo control. El porcentaje de neutrófilos que expresan CD62L se encontró significativamente disminuido en los pacientes con mayor compromiso inmunológico. Se observó una correlación positiva entre los niveles de LTCD4+ y el porcentaje de neutrófilos que expresan CD62L. Luego de 6 meses de tratamiento antirretroviral no hubo cambios significativos en los niveles de expresión de CD62L sobre LTCD4+ y LTCD8+. La reducción en los niveles de expresión de L-selectina en estos tipos celulares sugiere que durante la infección por HIV las funciones leucocitarias tales como la migración y el asentamiento linfocitario son anormales, contribuyendo al progresivo deterioro inmune.The ability of leukocytes to leave the circulation and migrate into tissues is a critical feature of the immune response. L-selectin (CD62L, the leukocyte selectin, mediates the binding of lymphocytes to high endothelial venules of peripheral lymph nodes and is also involved in lymphocyte, neutrophil and monocyte attachment to vascular endothelium at sites of inflammation. In this study L

  1. Effects of lithium on the functions of human neutrophils and lymphocytes in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, R.; Walters, L.; Grabow, G.; Van der Merwe, M.; Van Rensburg, C.E. (Pretoria Univ. (South Africa))

    1982-10-02

    The effects of lithium sulphate (LiSO/sub 4/) at concentrations ranging from 10/sup -7/M to 10/sup -2/M on human polymorphonuclear leucocyte (PMNL) and lymphocyte functions in vitro were investigated. The leucocyte functions assessed were PMNL motility, post-phagocytic hexose-monophosphate shunt activity, myeloperoxidase-mediated iodination of Candida albicans and lymphocyte transformation to mitogens. These same functions as well the results of serological studies were assessed in normal volunteers prior to ingestion of lithium carbonate (LiCO/sub 3/), 2 hours and 24 hours after the ingestion of a single oral dose of 480 mg LiCO/sub 3/ and on the 4th day of ingestion of 2x480 mg LiCO/sub 3/ tablets daily. Incubation of PMNL with LiSO/sub 4/ at concentrations up to 10/sup -3/M had no detectable effects on motility or post-phagocytic metabolic activity. Higher concentrations (10/sup -3/M) inhibited these functions. Likewise, at concentrations up to 1x10/sup -4/M LiSO/sub 4/ had no effects on mitogen-induced transformation of lymphocytes, although higher concentrations did inhibit this activity. These same leucocyte functions were unaffected by ingestion of LiCO/sub 3/. Levels of serum immunoglobulins and complement components, total haemolytic complement activity and salivary lgA values also remained unaltered. In vitro investigations showed that at a concentration of 10/sup -3/M LiSO/sub 4/ had no inhibitory effects on the stimulation of PMNL motility mediated by ascorbate, levamisole and thiamine.

  2. Neutrophil: Lymphocyte Ratio and Mean Platelet Volume in Patients with Gout

    Directory of Open Access Journals (Sweden)

    Ayse Balkarli

    2016-09-01

    Full Text Available Aim: Gout is a clinical syndrome with increased uric acid concentration, which is caused by inflammatory response against monosodium urate (MSU crystals. In gout, neutrophils are involved in inflammatory response and neutrophil activation is dependent on local cytokine production. Mean platelet volume (MPV and neutrophillymphocyte ratio (NLR are considered as inflammatory markers in several diseases and it is reported that they may have prognostic significance. Inthe current literature, there is no study evaluating MPV and NLR in gout. In this retrospective study, we investigated the role of MPV and NLR in determining inflammation in gout disease. Material and Method: In this retrospective study, 106 patients with gout (91 men and 15 women meeting the inclusion criteria based on patient records and 148 age- and sex-matched healthy controls (128 men and 20 women were included. Laboratory data during attacks (group I and intercritical period (group II were collected for the patient group. Results: Mean age was 59.46±12.93 years in the patient group and 59.00±11.33 years in the control group. Age at first attack was 52.00±12.77 years and mean time interval between first 2 attacks was 6.00±5.52 months. There was tophus in 9 patients (8.5% and family history of gout in 17 patients (16.0%. Compared to groupII (intercritical period and the control, no significant difference in MPV levels was found in groupI (during attack. MPV was similar among the three groups. C-reactive protein (CRP and erythrocyte sedimentation rate (ESR were found to be significantly higher in group I compared to group II. There was significant difference in NLR among three groups. When classified according to the presence of tophus, it was seen that MPV and NLR were similar in both groups. Discussion: The finding of increased NLR during attacks and intercritical period show that patients with gout are subjected to chronic inflammation. Thus, NLR can be a simple, inexpensive

  3. Type 1 Diabetes Prone NOD Mice Have Diminished Cxcr1 mRNA Expression in Polymorphonuclear Neutrophils and CD4+ T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    Karine Haurogné

    Full Text Available In humans, CXCR1 and CXCR2 are two homologous proteins that bind ELR+ chemokines. Both receptors play fundamental roles in neutrophil functions such as migration and reactive oxygen species production. Mouse Cxcr1 and Cxcr2 genes are located in an insulin-dependent diabetes genetic susceptibility locus. The non obese diabetic (NOD mouse is a spontaneous well-described animal model for insulin-dependent type 1 diabetes. In this disease, insulin deficiency results from the destruction of insulin-producing beta cells by autoreactive T lymphocytes. This slow-progressing disease is dependent on both environmental and genetic factors. Here, we report descriptive data about the Cxcr1 gene in NOD mice. We demonstrate decreased expression of mRNA for Cxcr1 in neutrophils and CD4+ lymphocytes isolated from NOD mice compared to other strains, related to reduced NOD Cxcr1 gene promoter activity. Looking for Cxcr1 protein, we next analyze the membrane proteome of murine neutrophils by mass spectrometry. Although Cxcr2 protein is clearly found in murine neutrophils, we did not find evidence of Cxcr1 peptides using this method. Nevertheless, in view of recently-published experimental data obtained in NOD mice, we argue for possible Cxcr1 involvement in type 1 diabetes pathogenesis.

  4. Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation.

    Science.gov (United States)

    Mukaida, N

    2000-12-01

    Since the discovery 13 years ago of interleukin (IL)-8 as a potent neutrophil chemotactic factor, accumulating evidence has established it as a crucial mediator in neutrophil-dependent acute inflammation. Numerous observations have demonstrated that various types of cells can produce a large amount of IL-8, either in response to various stimuli or constitutively, after malignant transformation. Recent studies of IL-8-mediated signaling have revealed that IL-8 activates a wide range of signaling molecules in a coordinate manner. IL-8 has been proven to have diverse actions on various types of leukocytic and nonleukocytic cells besides neutrophils. The author reviews recent progress in IL-8 signal transduction and biological actions on nonneutrophilic leukocytes, including T lymphocytes, monocytes, and hematopoietic progenitor cells. Potential involvement of IL-8 in viral infections and tumor progression is also discussed.

  5. Assessment of relationships between novel inflammatory markers and presence and severity of preeclampsia: Epicardial fat thickness, pentraxin-3, and neutrophil-to-lymphocyte ratio.

    Science.gov (United States)

    Cakmak, Huseyin Altug; Dincgez Cakmak, Burcu; Abide Yayla, Cigdem; Inci Coskun, Ebru; Erturk, Mehmet; Keles, Ibrahim

    2017-08-01

    The aim of this study was to evaluate the relation of three new inflammatory markers with presence and severity of preeclampsia and to compare the predictive values of all markers for presence of this setting. In this study, a total of 100 consecutive pregnants with a diagnosis of preeclampsia and 40 healthy pregnants between October 2014 and April 2015 were included. Epicardial fat tissue was calculated by two-dimensional transthoracic echocardiography, and pentraxin-3 and neutrophil-to-lymphocyte ratio were measured by using an enzyme-linked immunosorbent assay method and routine blood count analysis, respectively. Epicardial fat thickness (p preeclampsia as compared to the healthy pregnants. Furthermore, epicardial fat thickness (p = 0.002), pentraxin-3 (p preeclampsia compared to mild preeclampsia. In the multivariate analysis, epicardial fat thickness (p = 0.013), pentraxin-3 (p = 0.04), and neutrophil-to-lymphocyte ratio (p preeclampsia after adjusting for other risk factors. Epicardial fat thickness, neutrophil-to-lymphocyte ratio, and pentraxin-3 are important markers that provide an additional information beyond that provided by conventional methods in predicting presence and severity of preeclampsia.

  6. Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis.

    Directory of Open Access Journals (Sweden)

    Kyoung Im Cho

    Full Text Available Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS. We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR and major adverse cardiovascular events (MACE in patients with severe calcific AS.A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I and undergoing aortic valve replacement (AVR. We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period.The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR, 1.06; 95% confidence interval (CI, 1.04-1.09; p-value 9, respectively.The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS.

  7. Predictive value of elevated neutrophil to lymphocyte ratio in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction.

    Science.gov (United States)

    Ergelen, Mehmet; Uyarel, Huseyin; Altay, Servet; Kul, Şeref; Ayhan, Erkan; Isık, Turgay; Kemaloğlu, Tuba; Gül, Mehmet; Sönmez, Osman; Erdoğan, Ercan; Turfan, Murat

    2014-05-01

    The neutrophil to lymphocyte ratio (NLR) has been investigated as a new predictor for cardiovascular risk. Admission NLR would be predictive of adverse outcomes after primary angioplasty for ST-segment elevation myocardial infarction (STEMI). A total of 2410 patients with STEMI undergoing primary angioplasty were retrospectively enrolled. The study population was divided into tertiles based on the NLR values. A high NLR (n = 803) was defined as a value in the third tertile (>6.97), and a low NLR (n = 1607) was defined as a value in the lower 2 tertiles (≤6.97). High NLR group had higher incidence of inhospital and long-term cardiovascular mortality (5% vs 1.4%, P 6.97) was found as an independent predictor of inhospital cardiovascular mortality (odds ratio: 2.8, 95% confidence interval: 1.37-5.74, P = .005). High NLR level is associated with increased inhospital and long-term cardiovascular mortality in patients with STEMI undergoing primary angioplasty.

  8. Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

    Science.gov (United States)

    Zhou, Xin; Wang, Jing; Xia, Jun; Cheng, Feng; Mao, Jingjue; Zhu, Jianwei; Guo, Hongfeng

    2018-01-01

    The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

  9. Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in cervical cancer: a meta-analysis and systematic review.

    Science.gov (United States)

    Wu, Jiayuan; Chen, Manyu; Liang, Caixia; Su, Wenmei

    2017-02-21

    The prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in cervical cancer remains controversial. We conducted a meta-analysis based on the data from 13 studies with 3729 patients to evaluate the association between the pretreatment NLR and the clinical outcomes of overall survival and progression-free survival in patients with cervical cancer. The relationship between NLR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis indicated that elevated pretreatment NLR was a poor prognostic marker for patients with cervical cancer because it predicted unfavorable overall survival (HR = 1.375, 95% CI: 1.200-1.576) and progression-free survival (HR = 1.646, 95% CI: 1.313-2.065). Increased NLR is also significantly associated with the larger tumor size (OR = 1.780, 95% CI: 1.090-2.908), advanced clinical stage (OR = 2.443, 95% CI: 1.730-3.451), and positive lymph node metastasis (OR = 2.380, 95% CI: 1.775-3.190). By these results, high pretreatment NLR predicted a shorter survival period for patients with cervical cancer, and it could be served as a novel index of prognostic evaluation in patients with cervical cancer.

  10. Neutrophil-to-lymphocyte ratio and mural nodule height as predictive factors for malignant intraductal papillary mucinous neoplasms.

    Science.gov (United States)

    Watanabe, Yusuke; Niina, Yusuke; Nishihara, Kazuyoshi; Okayama, Takafumi; Tamiya, Sadafumi; Nakano, Toru

    2018-01-15

    Accurate preoperative prediction for malignant IPMN is still challenging. The aim of this study was to investigate the validity of neutrophil-to-lymphocyte ratio (NLR) and mural nodule height (MNH) for predicting malignant intraductal papillary mucinous neoplasm (IPMN). The medical records of 60 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. NLR tended to be higher in malignant IPMN (median: 2.23) than in benign IPMN (median: 2.04; p = .14). MNH was significantly greater in malignant IPMN (median: 16 mm) than in benign IPMN (median: 8 mm; p MNH were 3.60 and 11 mm, respectively. The sensitivity and specificity of NLR ≥3.60 for predicting malignant IPMN were 40% and 93%, and those of MNH ≥11 mm were 73% and 77%, respectively. Univariate analysis revealed that NLR ≥3.60 (p MNH ≥11 mm (p MNH ≥11 mm were not. NLR and MNH are suboptimal tests in predicting malignant IPMN; however, they can be useful to assist in clinical decision-making.

  11. Is the neutrophil-to-lymphocyte ratio a potential diagnostic marker for peptic ulcer perforation? A retrospective cohort study.

    Science.gov (United States)

    Tanrikulu, Yusuf; Sen Tanrikulu, Ceren; Sabuncuoglu, Mehmet Zafer; Kokturk, Furuzan; Temi, Volkan; Bicakci, Ercan

    2016-03-01

    Peptic ulcer perforation (PUP) accounts for 5% of all abdominal emergencies and is recognized as a gastrointestinal emergency requiring rapid and efficient clinical evaluation and treatment. The mortality rate ranges from 10% to 40% among patients with perforation. In the present retrospective study, we examined the potential utility of the neutrophil-to-lymphocyte ratio (NLR) in early diagnosis of PUP; we asked whether this ratio allowed PUP and peptic ulcer disease to be distinguished. We enrolled the following patients: 58 with PUP, 62 with noncomplicated peptic ulcer diseases (NCPU), and 62 controls, between May 2010 and 2015. Patients who underwent surgical repair to treat PUP were included in the study group. Another group consisted of NCPU patients who had a noncomplicated peptic ulcer. The control group consisted of patients presenting with nonspecific abdominal pain to the emergency department. The mortality rate was 5.2% in the PUP group. The white blood cell count, C-reactive protein, and NLRs were higher in the PUP compared to the other groups (Ppeptic ulcer disease. Thus, the NLR should be calculated in addition to the clinical examination. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with chronic hepatitis B virus (HBV) infection.

    Science.gov (United States)

    Zhao, Zhidan; Liu, Jianhua; Wang, Jiaxin; Xie, Tinyan; Zhang, Qiuhuan; Feng, Sisi; Deng, Hui; Zhong, Baiyun

    2017-10-01

    This retrospective study aimed to investigate the associations between the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and disease severity in patients with chronic HBV infection-related liver disease (CHB). Patients with CHB were retrospectively identified. Clinical data for 172 HBV-infected patients and 40 healthy controls were collected from the electronic patient medical record system database of our hospital. HBV-related-compensated-cirrhosis patients (HBV-CC patients) had a significantly lower mean PLR than did other patients (PHBV-related-decompensated-cirrhosis patients (HBV-DC patients) had a significantly higher mean NLR than did any other patients (PHBV DNA (r=0.264, PHBV DNA in both HBV-CC patients (r=-0.116, P=0.044) and HBV-DC patients (r=0.456, P=0.008). In HBV-Active-Carriers patients (HBV-AC patients), the PLR was positively correlated with serum HBeAg level (r=0.321, P=0.023). In HBV-DC patients, the NLR was positively correlated with serum HBeAg level (r=0.372, P=0.033). In the logistic regression prediction model, a predictive probability cutoff of 0.392 had the highest sensitivity and specificity (sensitivity, 91.2%; specificity, 84.0%) in distinguishing between HBV-CC and HBV-AC patients. A NLR cutoff value of 2.94 had the highest sensitivity and specificity (sensitivity, 81.8%; specificity, 88.2%) in distinguishing between HBV-DC and HBV-CC patients. The PLR and NLR partially reflect the amounts of serum HBV DNA and serum HBeAg levels circulating in CHB patients. The logistic regression model including the PLR and age most accurately distinguished between HBV-CC and HBV-AC patients. The NLR may be useful for follow-up in HBV-CC patients to predict disease progression. In summary, the PLR and NLR provided a supplementary means for effectively managing chronic HBV infection and disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Preoperative platelet-lymphocyte ratio is superior to neutrophil-lymphocyte ratio as a prognostic factor for soft-tissue sarcoma

    International Nuclear Information System (INIS)

    Que, Yi; Qiu, Haibo; Li, Yuanfang; Chen, Yongming; Xiao, Wei; Zhou, Zhiwei; Zhang, Xing

    2015-01-01

    Inflammation can promote tumor growth, invasion, angiogenesis and even metastasis. Inflammatory markers have been identified as prognostic indicators in various malignances. This study compared the usefulness of platelet-lymphocyte ratio (PLR) with that of neutrophil-lymphocyte ratio (NLR) for predicting outcomes of patients who underwent radical resection for soft tissue sarcoma (STS). We included 222 STS patients in this retrospective study. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate overall survival (OS) and disease free survival (DFS). In univariate analysis, elevated PLR and NLR were both significantly associated with decreased OS. In multivariate analysis, PLR (HR: 2.60; 95 % CI: 1.17–5.74, P = 0.019) but not NLR was still identified as independent predictors of outcome. Median OS was 62 and 76 months for the high PLR and low PLR groups, respectively. High PLR and NLR were both significantly associated with shorter DFS in univariate analysis, with median DFS of 18 and 57 months in the high PLR and low PLR groups. In multivariate analysis, elevated PLR (HR: 1.77; 95 % CI: 1.05–2.97, P = 0.032) was also related to decreased DFS. Our findings provide a new and valuable clue for diagnosing and monitoring STS. Prediction of disease progression is not only determined by the use of clinical or histopathological factors including tumor grade, tumor size, and tumor site but also by host-response factors such as performance status, weight loss, and systemic inflammatory response. They also significantly affect clinical outcomes. Thus, PLR can be used to enhance clinical prognostication. Furthermore, the PLR can be assessed from peripheral blood tests that are routinely available without any other complicated expenditure, thus providing lower cost and greater convenience for the prognostication. Elevated preoperative PLR as an independent prognostic factor is superior to NLR in predicting clinical outcome in patients with STS

  14. Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier.

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    Curis, Céline; Percher, Florent; Jeannin, Patricia; Montange, Thomas; Chevalier, Sébastien A; Seilhean, Danielle; Cartier, Luis; Couraud, Pierre-Olivier; Gout, Olivier; Gessain, Antoine; Ceccaldi, Pierre-Emmanuel; Afonso, Philippe V

    2016-08-15

    Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease develops upon infiltration of HTLV-1-infected lymphocytes into the central nervous system, mostly the thoracic spinal cord. The central nervous system is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. In this study, we investigated the role of activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, in the crossing of the BBB by HTLV-1-infected lymphocytes. We demonstrated that ALCAM is overexpressed on the surface of HTLV-1-infected lymphocytes, both in chronically infected cell lines and in primary infected CD4(+) T lymphocytes. ALCAM overexpression results from the activation of the canonical NF-κB pathway by the viral transactivator Tax. In contrast, staining of spinal cord sections of HAM/TSP patients showed that ALCAM expression is not altered on the BBB endothelium in the context of HTLV-1 infection. ALCAM blockade or downregulation of ALCAM levels significantly reduced the migration of HTLV-1-infected lymphocytes across a monolayer of human BBB endothelial cells. This study suggests a potential role for ALCAM in HAM/TSP pathogenesis. Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease is the consequence of the infiltration of HTLV-1-infected lymphocytes into the central nervous system (CNS), mostly the thoracic spinal cord. The CNS is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. The mechanism of migration of lymphocytes into the CNS is unclear

  15. Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history.

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    Ivković, Maja; Pantović-Stefanović, Maja; Dunjić-Kostić, Bojana; Jurišić, Vladimir; Lačković, Maja; Totić-Poznanović, Sanja; Jovanović, Aleksandar A; Damjanović, Aleksandar

    2016-04-01

    Neutrophil-to-lymphocyte ratio (NLR) has been independently related to bipolar disorder (BD) and factors associated with suicidal risk. The aim of our study was to explore the relationship between NLR and suicide risk in euthymic BD patients. We also sought to propose a model of interaction between NLR and stress-diathesis factors, leading to suicidal risk in BD. The study group consisted of 83 patients diagnosed with BD (36 suicide attempters; 47 suicide non-attempters), compared to the healthy control group (n=73) and matched according to age, gender, and body mass index (BMI). NLR was measured according to the complete blood count. Mood symptoms have been assessed by Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale. Early trauma and acute stress were evaluated by Early Trauma Inventory Self Report-Short Form and List of Threatening Experiences Questionnaire, respectively. Suicide risk has been assessed by Suicide Behaviors Questionnaire-Revised (SBQ-R). Significant correlation was found between NLR and SBQ-R score. The main effects of suicide attempts on NLR, after covarying for confounders, were observed, indicating increased NLR in BD suicide attempters compared to healthy controls. We found significant moderatory effects of family history on NLR relationship to suicidal risk, with NLR being significant positive predictor of suicidal risk only in the patients with positive family history of suicide attempts. The results suggest an enhancing effect of positive family history of suicide attempts on predictive effect of NLR on suicide risk. Our data support the idea that immune markers can predict suicide attempt risk in BD, but only in the subpopulation of BD patients with family history of suicide attempts. This could lead to prevention in suicide behavior in the patient population at particular risk of suicide. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma

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    Oh, Byong Sun; Jang, Jeong Won; Kwon, Jung Hyun; You, Chan Ran; Chung, Kyu Won; Kay, Chul Seung; Jung, Hyun Suk; Lee, Seungok

    2013-01-01

    Accumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC). The study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements. With the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, α-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p < 0.05). Patients with elevated CRP (> 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p < 0.001). The combined use of CRP and NLR provided incremental prognostic information. With significant inter-correlations, levels of CRP and NLR escalated with aggravating Child-Pugh class from A to C or progressing tumor stage from I to IV. CRP and NLR on baseline and serial measurements were well predictive of treatment response (p < 0.001). CRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC

  17. Pretreatment neutrophil to lymphocyte ratio in determining the prognosis of head and neck cancer: a meta-analysis.

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    Yu, Yalian; Wang, Hongbo; Yan, Aihui; Wang, Hailong; Li, Xinyao; Liu, Jiangtao; Li, Wei

    2018-04-04

    Recent studies have reported a relationship between prognosis and neutrophil-to-lymphocyte ratio (NLR) in patients with head and neck cancer (HNC). As the results are still controversial, we conducted a meta-analysis of pretreatment NLR in peripheral blood and prognosis in HNC patients. We retrieved articles from PubMed, Medline, Cochrane Library, Embase and Web of Science. A comparative analysis was conducted for the effect of pretreatment NLR in peripheral blood on overall survival (OS), progression-free survival, disease-free survival (DFS), disease-specific survival, metastasis-free survival, and recurrence-free survival of HNC patients. The analysis applied the criteria for systematic reviews described in the Cochrane Handbook and was conducted using hazard ratios (HRs) to estimate effect size, and calculated by Stata/SE version 13.0. The meta-analysis included eligible cohort studies (5475 cases). The OS data indicated increased mortality risk in HNC patients with a high NLR (HR = 1.84, 95% confidence interval (CI): 1.53-2.23; P Analysis of subgroups stratified by NLR cutoff values revealed increased mortality risk and significantly shorter DFS in patients with high NLR compared to those with low NLR (HR = 2.18, 95% CI: 1.46-3.24; P analysis results were stable, as shown by sensitivity analysis. No publication bias was detected by the Egger test (P = 0.135). HNC patients with elevated pretreatment NLR in peripheral blood have poor prognosis and are prone to local invasion and distant metastasis. NLR values are easily obtained from routinely collected blood samples and could assist clinicians to determine prognosis of HNC patients.

  18. Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Colorectal Liver Metastasis: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Tang, Haowen; Li, Bingmin; Zhang, Aiqun; Lu, Wenping; Xiang, Canhong; Dong, Jiahong

    2016-01-01

    Inflammation is deemed to play critical roles in tumor progression and metastasis, and an increased neutrophil-lymphocyte ratio (NLR) has been reported to correlate with poor survivals in various malignancies. However, association between NLR elevation and survival outcome in patients with colorectal liver metastasis (CRLM) remains controversial. The aim of this study was to investigate the prognostic significance of elevated NLR in CRLM. The meta-analysis was conducted in adherence to the MOOSE guidelines. PubMed, Embase, Cochrane Library, Web of Science and the Chinese SinoMed were systematically searched to identify eligible studies from the initiation of the databases to May, 2016. Overall survival (OS) and recurrence free survival (RFS) were pooled by using hazard ratio (HR) with corresponding 95% confidence interval (CI). Correlation between NLR values and clinicopathological features was synthesized by using odds ratio (OR) with corresponding 95% CI. A total of 1685 patients from 8 studies (9 cohorts) were analyzed, consisting 347 (20.59%) in high pretreatment NLR value group and 1338 (79.41%) in low pretreatment NLR value one. The results demonstrated that elevated pretreatment NLR was significantly related to poor OS (HR 2.17, 95% CI 1.82-2.58) and RFS (HR 1.96, 95% CI 1.64-2.35) in patients with CRLM. The result of this systematic review and meta-analysis indicated that an elevated pretreatment NLR was closely correlated with poor long-term survival (OS and RFS) in CRLM patients. NLR can be routinely monitored and serve as a useful and cost-effective marker with strong prognostic significance in patients with CRLM.

  19. Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis

    Science.gov (United States)

    Bowen, Randy C.; Little, Nancy Ann B.; Harmer, Joshua R.; Ma, Junjie; Mirabelli, Luke G.; Roller, Kyle D.; Breivik, Andrew Mackay; Signor, Emily; Miller, Alec B.; Khong, Hung T.

    2017-01-01

    An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS). We analyzed 144 studies comprising 45,905 patients, two-thirds of which were published after 2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001). This association was observed in all subgroups based on tumor site, stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70 (95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83 (95% CI, 1.50-2.23, P < 0.001), respectively. Available evidence suggests that NLR greater than the cutoff reduces OS, independent of geographic location, gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS also have worse outcomes with elevated NLR. PMID:28418870

  20. Comparison of carbon monoxide poisonings originated from coal stove and natural gas and the evaluation of Neutrophil/Lymphocyte ratio

    Directory of Open Access Journals (Sweden)

    Yahya Kemal Günaydın

    2015-09-01

    Full Text Available Objective: The aim of our study is to present the epidemiologic, clinical, laboratory and prognosis differences between the coal stove origin poisoning and natural gas leakages. We also aimed to investigate relationship between the severity of clinical picture, prognosis, complications develop in CO poisoning with neutrophil/lymphocyte ratio (NLR at the initial admission. Methods: All the acute carbon monoxide cases who applied to Ankara Training and Research Hospital Emergency Medicine Clinic between October 2009 and April 2010 were included to this prospective study. CO poisoning diagnosis was made by the history of CO poisoning with carboxyl hemoglobin (COHb concentration is over 10%. 100 patients were included to our study. Results: Of the patients, 55(55% were poisoned from the coal-stove and 45(45% from natural gas leakage. The mean COHb level of the natural gas group was significantly high (p=0.01. The mean value of GCS of the natural gas group was significantly lower (p=0.018. The number of patients with indication for HBO therapy were 17 and 6 in the natural gas group and coal-stove group, respectively, being significantly higher in the natural gas group(p=0.001. There was no statistically significant relationship between the value of NLR and values of COHb, troponin, and GCS (p=0.872, p=0.470, and p=0.896, respectively. Conclusions: Carbon monoxide poisoning from natural gas leakage is more toxic than that from the coal-stove. There is no relationship between NLR at the time of presentation and the severity of clinical findings, prognosis and complications.

  1. Preoperative lymphocyte-to-monocyte ratio represents a superior predictor compared with neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for colorectal liver-only metastases survival

    Directory of Open Access Journals (Sweden)

    Peng JH

    2017-07-01

    Full Text Available Jianhong Peng,1,* Hui Li,2,* Qingjian Ou,1,* Junzhong Lin,1 Xiaojun Wu,1 Zhenhai Lu,1 Yunfei Yuan,1 Desen Wan,1 Yujing Fang,1 Zhizhong Pan1 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Systemic inflammation was recognized as an essential factor contributing to the development of malignancies. This study aimed to investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR, neutrophil-to-lymphocyte ratio (NLR, and platelet-to-lymphocyte ratio (PLR in patients with colorectal liver-only metastases (CLOM undergoing hepatectomy. We retrospectively enrolled 150 consecutive patients with CLOM between 2000 and 2012. The optimal cutoff values of continuous LMR, NLR, and PLR were determined using the receiver operating characteristic curve analysis. Recurrence-free survival (RFS and overall survival (OS related to the LMR, NLR, and PLR were analyzed using both Kaplan–Meier and multivariate Cox regression methods. Elevated LMR (≥2.82 and lower NLR (<4.63 were significantly associated with better RFS and OS in patients with CLOM after hepatectomy, instead of lower PLR (<150.17. Multivariate Cox analysis identified elevated LMR as the only independent inflammatory factor for better RFS (hazard ratio, 0.591; 95% CI, 0.32–0.844; P=0.008 and OS (hazard ratio, 0.426; 95% CI, 0.254–0.716; P=0.001. In the subgroup analysis, elevated LMR was a significant favorable factor in both 5-year RFS and OS of patients with male gender, lymph node metastases, colon cancer, liver tumor with the largest diameter <5 cm, preoperative carcinoembryonic antigen level <200 ng/mL, negative hepatitis B virus infection, non

  2. The relationship between mean platelet volume and neutrophil/lymphocyte ratio with inflammation and proteinuria in chronic kidney disease

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    Gulay Yilmaz

    2017-01-01

    Full Text Available Atherosclerosis, which develops as a result of inflammation, is the most important cause of morbidity and mortality in chronic kidney disease (CKD. In this study, we investigated the relationship of mean platelet volume (MPV and neutrophil/lymphocyte ratio (NLR with inflammation and proteinuria in patients with CKD Stage 3-4. Healthy individuals who applied to nephrology clinic for checkup purposes acted as controls. Fifty-three patients and 30 healthy controls were included in the study. Patients with diabetes mellitus, active infection, malignancy, and coronary artery disease were excluded from the study. Biochemistry values and hemograms were recorded for all patients and for control group. NLR was calculated. The relationship between MPV/NLR and protein, fibrinogen, and proteinuria was evaluated. Our study showed a statistically significant difference between CKD group and healthy control (HC group in uric acid, fibrinogen, C-reactive protein, and NLR values (P <0.01, P <0.01, P = 0.01, P <0.01, respectively. No statistically significant difference was found between CKD and HC groups for MPV (P = 0.307. Correlation analysis revealed a statistically significant relationship between NLR and creatinine (P <0.00, r = 0.571, uric acid (P <0.00, r = 0.436, glomerular filtration rate (P <0.00, r = −0.418, 24 h urine protein (P = 0.004, r = 0.311, and 24 h urine microalbumin (P = 0.001, r = 0.354. A statistically significant relationship was detected between MPV and platelet count (P <0.001, r = −0.422, age (P = 0.004, r = −0.312, uric acid (P = 0.04, r = −0.226, and fibrinogen (P = 0.023, r = −0.249. Whereas, a statistically significant relationship was detected between NLR and microalbuminuria/proteinuria, there was no statistically significant relationship between MPV and microalbuminuria/proteinuria. Our study showed that the NLR is high in CKD group and is correlated with uric acid and proteinuria, which are known to be associated

  3. Elevated tissue transglutaminase antibodies in juvenile idiopathic arthritis children: Relation to neutrophil-to-lymphocyte ratio and disease activity

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    Rasha E. Gheith

    2017-10-01

    Full Text Available Background: Subclinical gut inflammation is described in juvenile idiopathic arthritis (JIA, so has joint involvement been related to celiac disease (CD. The well-known involvement of tissue transglutaminase (tTG in the pathogenesis of CD stimulated progress in the field of autoimmune diseases. Aim of the work: To screen JIA children for tTG antibodies and to detect its relation to the neutrophil-lymphocyte ratio (NLR and disease activity. Patients and methods: The study included 44 JIA children with 44 matched controls. All subjects had no GIT symptoms suggestive of CD. Disease activity was assessed using the juvenile arthritis disease activity score in 27 joints (JADAS-27. The tTG antibodies (IgA and IgG were assessed. Results: The patients mean age was 12.5 ± 2.8 years and disease duration 5.01 ± 2.9 years; Female:Male 3.4:1. The mean JADAS-27 score was 12.6 ± 2.04. tTG antibodies were positive in 43.2% of the patients compared to 18.2% control (p = 0.01. Antibodies positivity was comparable according to gender and subtypes. The NLR in JIA children (1.62 ± 0.58 was significantly higher than in control (1.3 ± 0.5 (p = 0.006. Those with positive tTG antibodies had a significantly reduced body mass index (p = 0.02 and increased NLR (p = 0.02 compared to those with negative tTG. Only NLR and JADAS-27 would significantly predict antibodies positivity (p = 0.037 and p = 0.04, respectively. Conclusion: Increased tTG antibodies are frequent in JIA children raising the possibility of an associated subclinical CD. Markedly reduced BMI and increased NLR could forecast the presence of these antibodies. In addition to the JADAS-27, the NLR is a simple test that could predict this association and could be a useful biomarker.

  4. Single emergency room measurement of neutrophil/lymphocyte ratio for early detection of acute kidney injury (AKI).

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    Abu Alfeilat, Mohsen; Slotki, Itzchak; Shavit, Linda

    2017-07-29

    Neutrophil-to-lymphocyte ratio (NLR) is considered a readily available biomarker of systemic inflammation. An association between elevated NLR and adverse outcomes in a variety of medical and surgical conditions including CKD has been demonstrated in several studies. In this study, we evaluated the accuracy of single Emergency Department (ED) measurement of NLR for early diagnosis of acute kidney injury (AKI). We prospectively studied 294 patients aged 71.6 ± 17. We measured NLR at presentation to the ED. AKI is defined as a new-onset 1.5-fold or more increase in serum creatinine or a 25% decrease in estimated GFR sustained for at least 3 days despite volume resuscitation. The primary outcome is AKI. Secondary outcome is in-hospital mortality. A multivariate model and ROC analysis were performed to evaluate the association and eventual predictive capacity of NLR for the outcomes. 36 patients (12.2%) developed AKI and 26 (9%) died, 8 (22%) of the AKI group and 17 patients (7%) of the non-AKI group. The Mean NLR is significantly higher in AKI compare to non-AKI patients (11.7 ± 15.2 vs 6.45 ± 7.19, p = 0.048). A multivariate model adjusted for age, gender, blood pressure, plasma albumin and hemoglobin levels confirms that the NLR is higher in AKI patients (p = 0.031). Receiver operating characteristics curve reveals an AUC of 0.715 (95% CI 0.63-0.8) sensitivity 0.78, specificity 0.65, and OR 6.423 (CI 2.659-16.026) for a cutoff value of NLR 5.5. The relation between NLR and in-hospital mortality is not statistically significant (p = 0.92). Single ED measurement of NLR might be a useful tool for early diagnosis of AKI. This finding is particularly important in light of the low cost and widespread availability of NLR, especially compared with other biomarkers currently under study in the context of AKI.

  5. Neutrophil to lymphocyte ratio as a reliable marker to predict insulin resistance and fibrosis stage in chronic hepatitis C virus infection.

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    Abdel-Razik, Ahmed; Mousa, Nasser; Besheer, Tarek A; Eissa, Mohamed; Elhelaly, Rania; Arafa, Mohammad; El-Wakeel, Niveen; Eldars, Waleed

    2015-12-01

    Hepatitis C virus (HCV) is one of the most noxious infectious diseases. Chronic hepatitis C (CHC) had biochemical evidence of insulin resistance (IR). The neutrophil/lymphocyte ratio (NLR) integrates information on the inflammatory milieu and physiological stress. We aimed to investigate the clinical utility of NLR to predict the presence of IR and fibrosis in CHCvirus infection. The study included 234 CHC patients and 50 healthy controls. The CHC group was divided into two subgroups ; CHC with HOMA-IR>3 and CHC with HOMA-IR≤3. Liver biopsy, homeostasis model assessment-IR (HOMA-IR), neutrophil and lymphocyte counts were recorded ; and NLR was calculated. Proinflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)] were measured by an enzyme-linked immunosorbent assay. Patients with HOMA-IR>3 had a higher NLR compared with patients with HOMA-IR≤3 [2.61±0.95 and 1.92±0.86, respectively, PC-reactive protein, TNF-α and IL-6 cytokines ; P3 and advanced fibrosis. This ratio can be used as a novel noninvasive marker to predict IR and advanced disease. © Acta Gastro-Enterologica Belgica.

  6. Effect of the level of maternal energy intake prepartum on immunometabolic markers, polymorphonuclear leukocyte function, and neutrophil gene network expression in neonatal Holstein heifer calves.

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    Osorio, J S; Trevisi, E; Ballou, M A; Bertoni, G; Drackley, J K; Loor, J J

    2013-06-01

    A conventional approach in dairy cow nutrition programs during late gestation is to feed moderate-energy diets. The effects of the maternal plane of nutrition on immune function and metabolism in newborn calves are largely unknown. Holstein cows (n=20) were fed a controlled-energy (CON) diet (1.24 Mcal/kg) for the entire dry period (~50 d) or the CON diet during the first 29 d of the dry period followed by a moderate-energy (OVE) diet (1.47 Mcal/kg) during the last 21 d prepartum. All calves were weighed at birth before first colostrum intake. Calves chosen for this study (n=6 per maternal diet) had blood samples harvested before colostrum feeding (d 0) and at 2 and 7 d of age. Blood samples were used to determine metabolites, acute-phase proteins, oxidative stress markers, hormones, phagocytic capacity of polymorphonuclear leukocytes (PMN) and monocytes, and total RNA was isolated from PMN. Calves from OVE dams weighed, on average, 5kg less at birth (44.0 vs. 48.6kg) than calves from CON dams. Blood glucose concentration in OVE calves had a more pronounced increase between 0 and 2 d than CON, at which point phagocytosis by PMN averaged 85% in OVE and 62% in CON. Compared with CON, calves from OVE had greater expression of TLR4, but lower expression of PPARA and PPARD at birth. Expression of PPARG and RXRA decreased between 0 and 2 d in both groups. Concentrations of leptin, cholesterol, ceruloplasmin, reactive oxygen metabolites, myeloperoxidase, retinol, tocopherol, IgG, and total protein, as well as expression of SOD2 and SELL increased markedly by 2 d in both groups; whereas, cortisol, albumin, acid-soluble protein, NEFA, insulin, as well as expression of IL6, TLR4, IL1R2, LTC4S, and ALOX5 decreased by 2 d. By 7 d of age, the concentration of haptoglobin was greater than precolostrum and was lower for OVE than CON calves. Our data provide evidence for a carry-over effect of maternal energy overfeeding during the last 3 wk before calving on some measurements of

  7. Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study.

    Science.gov (United States)

    Borné, Yan; Smith, J Gustav; Nilsson, Peter M; Melander, Olle; Hedblad, Bo; Engström, Gunnar

    2016-01-01

    High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes. Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45-73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22-1.53) for total leukocytes, 1.33 (1.19-1.49) for neutrophils and 1.29 (1.15-1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes. Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations

  8. Decline of blood leukocyte counts 1947-59, Hiroshima and Nagasaki

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    Ichimaru, Michito; Ueda, Shoichi; Blaisdell, R K

    1963-03-03

    Earlier reports of progressive decline in leukocyte counts in Hiroshima from about 1948 to 1954 have been confirmed. A similar phenomenon has been observed in Nagasaki. Analysis indicates that this decline in white cell count with time is not related to exposure to the 1945 atomic bombs, to sex, to age, to commonly diagnosed diseases, or to the disproportionate influence of a subgroup. The principal white cells affected were neutrophils, lymphocytes and eosinophils. The precise etiologic factors accounting for the decline, and the biological significance of the present lower range of leukocyte values in Hiroshima and Nagasaki remain to be determined. 16 references, 5 figures, 5 tables.

  9. Quantitative and qualitative changes in leukocytes of psoriatic patients

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    Mahesar, S.M.; Khand, A.A.

    2011-01-01

    Background: Psoriasis is a disease concerned with inflammation and scaling of skin. In psoriasis, cells of the skin come on surface quickly before their complete maturation. In psoriatic patients, T-cells produce an abnormally large amount of toxic chemicals and cause inflammation. This study was undertaken to find out values of prognostic significance for worsening of the disease at early stage and to evaluate the changes (quantitative and qualitative) occurring in white blood cells of psoriatic patients. Methods: A total of 158 subjects, 79 psoriatic patients (44 males and 35 females) and same numbers of normal control volunteers were recruited. Total and Differential Leukocyte Counts (TLC and DLC) were determined. Morphological examination was also undertaken. All results of patients were compared with normal control volunteers. Results : In 47.7% male and 54.2% female patients TLC was higher than controls while variation in differential count was observed in 61.3% male and 62.8% female patients. Overall, neutrophils in 45% patients, basophils in 30.3%, eosinophils in 65.8%, and monocytes in 15% of patients were elevated. In 77.2% psoriatic patients, lymphocytes were decreased. In volunteers total and differential leukocyte counts were within normal range. Total leukocyte count in normal males was 5,136 +- 31, and in psoriatic male subjects it was 10,498 +- 43, and it was 5,023 +- 35 against 11,390 +- 31 in normal versus psoriatic females ( p<0.001). Conclusion: Total leukocyte count was elevated in psoriatics while on DLC neutrophils, eosinophils and neutrophils were significantly raised where as lymphocytes were significantly decreased in psoriatic patients. Morphological changes were also noted. (author)

  10. Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation

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    Shen, Lijun; Zhang, Hui; Liang, Liping; Li, Guichao; Fan, Ming; Wu, Yongxin; Zhu, Ji; Zhang, Zhen

    2014-01-01

    The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer. From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed. With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0–1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2–3 group with no statistical significance (P = 0.873). An elevated baseline NLR is a valuable and easily available prognostic factor for OS in

  11. In vitro studies of leukocyte labeling with /sup 99m/Tc

    International Nuclear Information System (INIS)

    Uchida, T.; Vincent, P.C.

    1976-01-01

    A method for labeling leukocytes in vitro with /sup 99m/Tc is described. Separated leukocytes are incubated with /sup 99m/Tc, followed by reduction with stannous chloride and washing with acid citrate dextrose solution. Maximum labeling occurs after at least 5 min incubation with pertechnetate, followed by at least 10 min incubation with stannous chloride. Labeling is similar at room temperature and at 37 0 C. The labeled leukocytes are viable, and reutilization of label does not occur in vitro. In acid conditions (pH 5.2), the elution of /sup 99m/Tc from leukocytes is comparable with that of 32 P-diisopropylfluorophosphate, but /sup 99m/Tc elution is greater at pH 7.2 to 7.4. Neutrophils label more heavily with /sup 99m/Tc than do monocytes, lymphocytes, erythrocytes, or platelets

  12. Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis.

    Science.gov (United States)

    Jeon, Tae Joo; Park, Ji Young

    2017-06-07

    To investigated the prognostic value of the neutrophil-lymphocyte ratio (NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients. We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d (median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P pancreatitis. Elevated baseline NLR correlates with severe acute pancreatitis and organ failure.

  13. White blood cell counts and neutrophil to lymphocyte ratio in the diagnosis of testicular cancer: a simple secondary serum tumor marker.

    Science.gov (United States)

    Yuksel, Ozgur Haki; Verit, Ayhan; Sahin, Aytac; Urkmez, Ahmet; Uruc, Fatih

    2016-01-01

    The aim of the study was to investigate white blood cell counts and neutrophil to lymphocyte ratio (NLR) as markers of systemic inflammation in the diagnosis of localized testicular cancer as a malignancy with initially low volume. Thirty-six patients with localized testicular cancer with a mean age of 34.22±14.89 years and 36 healthy controls with a mean age of 26.67±2.89 years were enrolled in the study. White blood cell counts and NLR were calculated from complete blood cell counts. White blood cell counts and NLR were statistically significantly higher in patients with testicular cancer compared with the control group (ptesticular cancer besides the well-known accurate serum tumor markers as AFP (alpha fetoprotein), hCG (human chorionic gonadotropin) and LDH (lactate dehydrogenase).

  14. Neutrophil to lymphocyte ratio (NLR) improves the risk assessment of ISS staging in newly diagnosed MM patients treated upfront with novel agents.

    Science.gov (United States)

    Romano, A; Parrinello, N L; Consoli, M L; Marchionni, L; Forte, S; Conticello, C; Pompa, A; Corso, A; Milone, G; Di Raimondo, F; Borrello, I

    2015-11-01

    Recent reports identify the ratio between absolute neutrophil count (ANC) and absolute lymphocyte count (ALC), called neutrophil to lymphocyte ratio (NLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. We retrospectively examined the NLR in a cohort of 309 newly diagnosed multiple myeloma (MM) patients treated upfront with novel agents. NLR was calculated using data obtained from the complete blood count (CBC) at diagnosis and subsequently correlated with PFS and OS. The median NLR was 1.9 (range 0.4-15.9). Higher NLR was independent of international staging system (ISS) stage, plasma cell infiltration or cytogenetics. The 5-year PFS and OS estimates were, respectively, 18.2 and 36.4 % for patients with NLR ≥ 2 versus 25.5 and 66.6 % in patients with NLR < 2. Among younger patients (age <65 years, N = 179), NLR ≥ 2 had a negative prognostic impact on both PFS and OS, in all ISS stages. By combining ISS stage and NLR in a model limited to young patients, we found that 19 % of the patients were classified as very low risk, 70 % standard risk and 11 % very high risk. The 5-year estimates were 39.3, 19.4 and 10.9 % for PFS and 95.8, 50.9 and 23.6 % for OS for very low, standard-risk and very high-risk groups. We found NLR to be a predictor of PFS and OS in MM patients treated upfront with novel agents. NLR can be combined with ISS staging system to identify patients with dismal outcome. However, larger cohorts and prospective studies are needed to use NLR as additional parameter to personalise MM therapy in the era of novel agents.

  15. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

    Science.gov (United States)

    Viswanathan, Kavitha; Dhabhar, Firdaus S.

    2005-04-01

    Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

  16. TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils

    DEFF Research Database (Denmark)

    Radjabova, Valeria; Mastroeni, Piero; Skjødt, Karsten

    2015-01-01

    We identified a novel, evolutionarily conserved receptor encoded within the human leukocyte receptor complex and syntenic region of mouse chromosome 7, named T cell-interacting, activating receptor on myeloid cells-1 (TARM1). The transmembrane region of TARM1 contained a conserved arginine residu...

  17. LEUKOCYTE DIFFERENTIAL OF ANGUILLID EEL, Anguilla bicolor McClelland, EXPOSED TO VARIED SALINITIES

    Directory of Open Access Journals (Sweden)

    Fita Fatimah

    2017-06-01

    Full Text Available The anguillid eel is a catadromous eel capable of inhabiting freshwater growth habitat and seawater spawning habitat throughout their life cycle. At the juvenile to mature stage, they inhabit freshwater then migrate to marine water to spawn. Changes in salinity, which is one of the stressful environmental factors for the eel, affect their physiological condition by increasing the leukocytes number. This increase is an adaptation method to improve their immune system as a response to salinity change. This study intended to evaluate the leukocyte differential of anguillid eel (Anguilla bicolor McClelland exposed to various salinities. This research applied a Completely Randomized Design. The treatment was three levels of saline media including 4 ppt, 15 ppt, and 30 ppt with five replicates. The independent variable was the different salinity, and the dependent variable was the leukocyte differential. The parameters measured consisted of the different percentage of neutrophils, lymphocytes, monocytes, and eosinophils in which the measurements administered after two months of the eel exposure. We analyzed the data with ANOVA at the confidence level of 95%. The results showed that exposure of salinity significantly affected the percentage of leukocyte differential (P < 0.05. The increase in salinity decreased the neutrophils and monocytes, but increased the lymphocytes, and showed no effect on eosinophils.

  18. Association between circulating specific leukocyte types and incident chronic kidney disease: the Atherosclerosis Risk in Communities (ARIC) study.

    Science.gov (United States)

    Tian, Niu; Penman, Alan D; Manning, R Davis; Flessner, Michael F; Mawson, Anthony R

    2012-01-01

    Progressive renal fibrosis is a characteristic of all the diseases that cause renal failure and is invariably accompanied by a prominent leukocyte infiltration in the kidney. The goal of this study was to determine the association between the circulating specific leukocyte types and incident chronic kidney disease (CKD). In a cohort of 10,056 middle-aged white and African American adults, levels of circulating neutrophils, lymphocytes, and monocytes were measured at baseline; blood pressure (BP) and serum creatinine were measured and estimated glomerular filtration rate (eGFR) was calculated at baseline and 3 and 9 years later; and surveillance for first hospitalization or death with CKD was carried out over a mean follow-up of 7.4 years (maximum, 11.9 years). Increased neutrophil levels and decreased lymphocyte levels were significantly associated with greater CKD incidence after adjustment for covariates. African Americans tended to have similar but stronger patterns of association between circulating leukocytes and CKD incidence than whites, although the differences between race groups were not statistically significant. We also found that eGFR and BP were higher at each visit in African Americans than whites between ages 45 and 65. These findings support a potential role for circulating specific leukocytes in the pathogenesis of kidney dysfunction, especially in African Americans, indicating the leukocyte-related renal mechanism of essential hypertension (HT). Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  19. Peripheral blood and milk leukocytes subsets of lactating Sarda ewes

    Directory of Open Access Journals (Sweden)

    Piero Bonelli

    2013-05-01

    Full Text Available Leukocytes subpopulations in blood and milk of lactating Sarda ewes were investigated. Animals characterized by a SSC level <500×103cells/mL and a negative bacteriological examination were sampled in early, mid and late lactation. Milk differential cell count evidenced that macrophage represented the main population (42.8%±3.5 followed by lymphocytes (40.2%±3.4 and neutrophils (8,6%±2.1. Flow cytometry analysis showed that lymphocytes subsets in milk were quite different from blood. High CD8+ and low CD4+ lymphocytes percentages determined a CD4/CD8 ratio inversion in milk compared to blood (0.3%±0.03 vs 1.8%±0.08. CD8+ decreased while, conversely, CD4+ increased in late lactation. γδ T cells were more represented in milk (12.6%±1.3 than in blood (6.8%±0.3 and their proportions appeared similar throughout lactation in both compartments. IL-2 receptor was mainly expressed in milk on T cytotoxic lymphocytes. Data obtained in uninfected mammary glands could allow an early discrimination between physiological and pathological changes occurring in ewe milk. Further phenotypical and functional studies on milk leukocytes subsets might help to understand defense mechanisms of the ovine mammary gland against IMI.

  20. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Sacdalan DB

    2018-02-01

    Full Text Available Danielle Benedict Sacdalan,1 Josephine Anne Lucero,2 Dennis Lee Sacdalan1 1Section of Medical Oncology, Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines; 2Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines Introduction: Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients.Methods: We performed a meta-analysis of published articles on the utility of baseline NLR in predicting outcomes in patients treated with immune checkpoint inhibitors (ICIs using Review Manager, version 5.3. Seven studies on the prognostic utility of NLR in ICI treatment were included in this analysis. For outcomes of interest, the hazard ratios (HRs were computed. Subgroup analyses were planned based on type of malignancy and type of immune checkpoint inhibitor.Results/discussion: A high NLR resulted in worse overall survival (OS (HR, 1.92; 95% CI, 1.29–2.87; p=0.001 and progression-free survival (PFS; HR, 1.66; 95% CI, 1.38–2.01; p<0.00001 across types of malignancies studied (melanoma, non-small-cell lung cancer, and genitourinary cancer. Subgroup analysis across different types of malignancies treated with ICI showed similar results for OS and PFS. The single study on genitourinary cancers also showed worse OS and PFS (OS: HR, 1.82; 95% CI, 1.29–2.87; p=0.001 and PFS: HR, 1.83; 95% CI, 0.97–3

  1. Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet Count, CRP, and Albumin Levels in Metastatic Colorectal Cancer Patients Treated with FOLFIRI-Bevacizumab.

    Science.gov (United States)

    Artaç, Mehmet; Uysal, Mükremin; Karaağaç, Mustafa; Korkmaz, Levent; Er, Zehra; Güler, Tunç; Börüban, Melih Cem; Bozcuk, Hakan

    2017-06-01

    Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil-leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach. Hence, there is a strong need for identifying new prognostic factors to show the efficacy of FOLFIRI-bev. This is a retrospective study including patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded before FOLFIRI-bev therapy. The efficacy of these factors on progression-free survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And the cutoff value of N/L ratio was analyzed with ROC analysis. The median age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio >2.5 showed progressive disease versus 43 % in patients with N/L ratio ratio >2.5 versus 13.5 months for the patients with N/L ratio analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were all significantly associated with poor prognosis. At multivariate Cox regression analysis, CRP was confirmed to be a better independent prognostic factor. CRP variable was divided into above the upper limit of normal (ULN) and normal value. The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8 months, respectively (p = 0.022). CRP and N/L ratio are potential predictors for advanced mCRC treated with FOLFIRI-bev.

  2. Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial.

    Science.gov (United States)

    Liu, Yanhong; Kong, Xiangyi; Wang, Wen; Fan, Fangfang; Zhang, Yan; Zhao, Min; Wang, Yi; Wang, Yupeng; Wang, Yu; Qin, Xianhui; Tang, Genfu; Wang, Binyan; Xu, Xiping; Hou, Fan Fan; Gao, Wei; Sun, Ningling; Li, Jianping; Venners, Scott A; Jiang, Shanqun; Huo, Yong

    2017-01-01

    The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all P dyslipidemia/normolipidemia), we found that patients in the highest quartile of total leukocyte count (≥7.6 × 10 9 cells/l) had 1.64 times the risk of high TG [95% confidence interval (CI): 1.46, 1.85], 1.34 times the risk of high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI: 1.12, 1.39) compared with their counterparts in the lowest quartile of total leukocyte count. Similar patterns were also observed with neutrophils and lymphocytes. In summary, these findings indicate that elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  3. Neutrophil and lymphocyte dose curves in whole-body relatively homogeneous human γ-irradiation (on the basis of the materials of the accident at the Chernobyl Nuclear Power Station)

    International Nuclear Information System (INIS)

    Konchalovskij, M.V.; Baranov, A.E.; Solov'ev, V.Yu.

    1991-01-01

    The experience in a study of regularties of the bone marrow syndrome in persons exposed to rather homogeneous γ-beam irradiation during the accident at the Chernobyl Nuclear Power Station (127 cases) were summed up. Hematological data were processed by computer, and emperic dose curves of neutrophils and lymphocytes were obtained within the range of 0.5-12 Gy by regressive analysis. New data were obtained on the nature of a course of a granulocyte recovery phase at a dose level over 5 Gy. Some features of the time course of lymphocytes in persons exposed to radiation during the accident at the Chernobyl Nuclear Power Station, were considered

  4. Association of the Preoperative Neutrophil-to-ymphocyte Count Ratio and Platelet-to-Lymphocyte Count Ratio with Clinicopathological Characteristics in Patients with Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Sang Mi Kim

    2015-12-01

    Full Text Available BackgroundSeveral inflammatory biomarkers, especially a high preoperative neutrophil-to-lymphocyte count ratio (NLR and platelet-to-lymphocyte count ratio (PLR, are known to be indicator of poor prognosis in several cancers. However, very few studies have evaluated the significance of the NLR and PLR in papillary thyroid cancer (PTC. We evaluated the association of the preoperative NLR and PLR with clinicopathological characteristics in patients with PTC.MethodsThis study included 1,066 female patients who underwent total thyroidectomy for PTC. Patients were stratified into 4 quartiles by preoperative NLR and PLR. And the combination of preoperative NLR and PLR was calculated on the basis of data obtained value of tertile as follows: patients with both an elevated PLR and an elevated NLR were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively.ResultsThe preoperative NLR and PLR were significantly lower in patients aged ≥45 years and in patients with Hashimoto's thyroiditis. The PLR was significantly higher in patients with tumor size >1 cm (P=0.021.When the patients were categorized into the aforementioned four groups, the group with the higher preoperative PLR was found to have a significantly increased incidence of lateral lymph node metastasis (LNM (P=0.018. However, there are no significant association between the combination of preoperative NLR and PLR and prognostic factors in PTC patients.ConclusionThese results suggest that a preoperative high PLR were significant associated with lateral LNM in female patients with PTC.

  5. Relationships between leukocytes and Hepatozoon spp. In green frogs, Rana clamitans.

    Science.gov (United States)

    Shutler, Dave; Smith, Todd G; Robinson, Stephen R

    2009-01-01

    There are few published data on amphibian leukocyte profiles, and relationships between amphibian leukocytes and parasites are even less well known. Using counts from 35 pairs of blood smears taken 2 days apart, we tested for correlations between leukocyte proportions and infection intensities of Hepatozoon spp. (either Hepatozoon catesbianae or Hepatozoon clamatae) in green frogs (Rana clamitans). On average (SE), we counted 65.4 (1.7) lymphocytes, 14.0 (1.3) neutrophils, 19.3 (1.6) eosinophils, 0.9 (0.1) monocytes, and 0.4 (0.1) basophils per 100 leukocytes. All frogs harbored Hepatozoon spp. (median seven parasites per 100 leukocytes; range 1-250). Significant relationships were not observed between numbers of leukocytes and infection intensities of Hepatozoon spp. Among the possible explanations for these null results are that Hepatozoon spp. is benign, that Hepatozoon spp. is able to evade detection by the immune system, that Hepatozoon spp. is able to manipulate leukocyte investment, or that other unmeasured or undetected parasites were more important in affecting immune response.

  6. Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake

    DEFF Research Database (Denmark)

    Inturi, Swetha; Wang, Guankui; Chen, Fangfang

    2015-01-01

    demonstrated that neutrophils, monocytes, lymphocytes and eosinophils took up SPIO NWs, and the uptake was prevented by EDTA (a general complement inhibitor) and by antiproperdin antibody (an inhibitor of the alternative pathway of the complement system). Cross-linking and hydrogelation of SPIO NWs surface...... by epichlorohydrin decreased C3 opsonization in mouse serum, and consequently reduced the uptake by mouse leukocytes by more than 70% in vivo. Remarkably, the cross-linked particles did not show a decrease in C3 opsonization in human serum, but showed a significant decrease (over 60%) of the uptake by human...... leukocytes. The residual uptake of cross-linked nanoparticles was completely blocked by EDTA. These findings demonstrate species differences in complement-mediated nanoparticle recognition and uptake by leukocytes, and further show that human hemocompatibility could be improved by inhibitors of complement...

  7. Can the neutrophil-to-lymphocyte ratio be used to predict recurrence and progression of non-muscle-invasive bladder cancer?

    Directory of Open Access Journals (Sweden)

    Sebahattin Albayrak

    2016-06-01

    Full Text Available The aim of our study was to evaluate whether neutrophil-to-lymphocyte ratio (NLR is a predictor of disease progression and recurrence in patients with primary non-muscle-invasive bladder cancer (NMIBC. This was a prospective study of 86 patients with newly diagnosed NMIBC. The patients were classified by the number of points assigned by the European Organization for Research and Treatment of Cancer risk tables. The correlation between progression score, recurrence score, age, mean platelet volume, red blood cell distribution width and NLR was assessed statistically. The same parameters were compared between the risk groups. A significant difference in NLR and age values was observed between recurrence and progression risk score groups. The relationships between NLR and recurrence and progression risk scores were no longer significant after correcting for the statistical effect of age on scores. Age was significantly different between groups after adjusting for NLR. Our study revealed that NLR and age were associated with patient age and bladder tumor progression and recurrence risk scores. After correcting for age, the significant relationship with NLR was lost, in contrast to some previous studies. We recommend that patient age should be corrected to avoid misleading results in NLR studies.

  8. The pretransplant neutrophil-lymphocyte ratio as a new prognostic predictor after liver transplantation for hepatocellular cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Xu, Zheng-Guang; Ye, Cheng-Jie; Liu, Lin-Xun; Wu, Gang; Zhao, Zhan-Xue; Wang, Yong-Zhen; Shi, Bing-Qiang; Wang, Yong-Hong

    2018-02-01

    Recently, many reports showed that the pretransplant neutrophil-lymphocyte ratio (NLR) may be correlated with the prognosis of patients undergoing liver transplantation (LT) for hepatocellular cancer (HCC). However, their results still remained controversial. Thus we performed a meta-analysis of 13 studies to estimate the prognostic value of pretransplant NLR. Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to September 2017. Hazard ratio (HR) or odds ratio (OR) with its 95% CI was used to evaluate the association between elevated NLR and the prognosis or clinical features of liver cancer patients. A total of 13 studies including 1936 patients were included in this meta-analysis. Elevated pretransplant NLR had a close association with the overall survival (HR: 2.22; 95% CI: 1.34-3.68), recurrence-free survival (HR: 3.77; 95% CI: 2.01-7.06) and disease-free survival (HR: 2.51; 95% CI: 1.22-5.15) of patients undergoing LT for HCC, respectively. In addition, elevated NLR was associated with the presence of vascular invasion (OR: 2.39; 95% CI: 1.20-4.77) and Milan criteria (OR: 0.26; 95% CI: 0.17-0.40). The results of this meta-analysis showed that elevated pretransplant NLR may be used as a new prognostic predictor after LT for HCC.

  9. Postoperative Neutrophil-to-Lymphocyte Ratio as a Predictor of Long-Term Prognosis after Pancreatectomy for Pancreatic Carcinoma: A Retrospective Analysis.

    Science.gov (United States)

    Tsujita, Eiji; Ikeda, Yasuharu; Kinjo, Nao; Yamashita, Yo-Ichi; Hisano, Terumasa; Furukawa, Masayuki; Taguchi, Ken-Ichi; Morita, Masaru; Toh, Yasushi; Okamura, Takeshi

    2017-06-01

    To clarify the prognostic value of the postoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing pancreatectomy for pancreatic carcinoma (PAC). A high preoperative NLR has been reported to be a predictor of poor survival in patients with various cancers including PAC. However, it has not been extensively examined in postoperative NLR after pancreatectomy for PAC. This retrospective study enrolled 86 patients who underwent pancreatectomy without preoperative therapy for PAC from 2005 to 2013. Clinicopathological parameters, including postoperative NLR, were evaluated to identify predictors of the overall and recurrence-free survival of patients after pancreatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. Univariate and multivariate analyses showed that postoperative NLR at one month was an independent prognostic factor in the overall and recurrence-free survival of patients. The 3-year survival rate after pancreatectomy was as follows: 33.9 per cent in patients with a postoperative NLR of less than 3.0 at one month; and 7.3 per cent in those with a postoperative NLR of 3.0 or more at one month (P pancreatectomy in the NLR at one month ≥3.0 group was significantly lower than in the NLR at one month pancreatectomy in patients with PAC.

  10. An elevated neutrophil-lymphocyte ratio is associated with adverse outcomes following single time-point paracetamol (acetaminophen) overdose: a time-course analysis.

    Science.gov (United States)

    Craig, Darren G; Kitto, Laura; Zafar, Sara; Reid, Thomas W D J; Martin, Kirsty G; Davidson, Janice S; Hayes, Peter C; Simpson, Kenneth J

    2014-09-01

    The innate immune system is profoundly dysregulated in paracetamol (acetaminophen)-induced liver injury. The neutrophil-lymphocyte ratio (NLR) is a simple bedside index with prognostic value in a number of inflammatory conditions. To evaluate the prognostic accuracy of the NLR in patients with significant liver injury following single time-point and staggered paracetamol overdoses. Time-course analysis of 100 single time-point and 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Timed laboratory samples were correlated with time elapsed after overdose or admission, respectively, and the NLR was calculated. A total of 49/100 single time-point patients developed hepatic encephalopathy (HE). Median NLRs were higher at both 72 (P=0.0047) and 96 h after overdose (P=0.0041) in single time-point patients who died or were transplanted. Maximum NLR values by 96 h were associated with increasing HE grade (P=0.0005). An NLR of more than 16.7 during the first 96 h following overdose was independently associated with the development of HE [odds ratio 5.65 (95% confidence interval 1.67-19.13), P=0.005]. Maximum NLR values by 96 h were strongly associated with the requirement for intracranial pressure monitoring (Pparacetamol overdoses. Future studies should assess the value of incorporating the NLR into existing prognostic and triage indices of single time-point paracetamol overdose.

  11. Elevated Preoperative Neutrophil-Lymphocyte Ratio Is Associated with Poor Prognosis in Hepatocellular Carcinoma Patients Treated with Liver Transplantation: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Sun

    2016-01-01

    Full Text Available This study aims to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR in hepatocellular carcinoma (HCC patients treated with liver transplantation (LT through meta-analysis. Relevant articles were sought in PubMed, Embase, and Wangfang databases up to July 2015. A total of 1687 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that elevated NLR was significantly associated with poorer overall survival (OS (HR = 2.71, 95% CI: 1.91–3.83 and poorer disease-free survival (DFS (HR = 3.61, 95% CI: 2.23–5.84 in HCC patients treated with LT. Moreover, subgroup analysis showed the significant association between elevated preoperative NLR and poor prognosis was not altered by cutoff values of NLR or types of LT. Therefore, elevated preoperative NLR is associated with poor prognosis in HCC patients treated with LT. Preoperative NLR should be used to predict the prognosis of HCC after LT in our clinical work.

  12. Neutrophil-to-lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3-year follow-up study).

    Science.gov (United States)

    Azab, Basem; Daoud, Jacques; Naeem, Fahad Ben; Nasr, Rabih; Ross, Jennifer; Ghimire, Pratima; Siddiqui, Ayesha; Azzi, Nadine; Rihana, Nancy; Abdallah, Marie; Azzi, Nassif; Patel, Parishram; Kleiner, Morton; El-Sayegh, Suzanne

    2012-01-01

    Previous studies have demonstrated the role of inflammation in diabetic nephropathy (DN). Neutrophil to lymphocyte ratio (NLR) rather than other white cell parameters was found to be a useful inflammatory marker to predict adverse outcomes in medical and surgical conditions. Nevertheless, the value of NLR in predicting DN has not been elucidated. An observational study included 338 diabetic patients, who were followed at our clinic between 2007 and 2009. We arranged our patients into tertiles according to their 2007 NLR. The primary outcome was continuous decrease of GFR >12 mL/min between 2007 and 2009 with the last GFR <60 mL/min. The lowest NLR tertile had fewer patients (2.7%) with primary outcome (i.e., worsening renal function) compared with middle and highest NLR tertiles, which had more patients with primary outcomes (8.7% and 11.5%, respectively) with a significant p-value 0.0164. When other potential confounders were individually analyzed with NLR tertile, the NLR tertiles remained a significant predictor of poor GFR outcome in the presence of other variables (hemoglobin A1C, systolic blood pressure, diastolic blood pressure, age, and congestive heart failure with p-values 0.018, 0.019, 0.017, 0.033, and 0.022, respectively). NLR predicted the worsening of the renal function in diabetic patients. Further studies are needed to confirm this result.

  13. The connections among suicidal behavior, lipid profile and low-grade inflammation in patients with major depressive disorder: a specific relationship with the neutrophil-to-lymphocyte ratio.

    Science.gov (United States)

    Ekinci, Okan; Ekinci, Asli

    2017-11-01

    The role of inflammation and lipid metabolism in the pathophysiology of suicidal behavior has received particular attention in recent years. The neutrophil-to-lymphocyte ratio (NLR) has been suggested as a new and more reliable indicator of low-grade inflammation. NLR has been found to be altered in major depressive disorder (MDD) and has been related to various factors, including chronic stress and impulsivity that were previously reported to be related to suicidal behavior. We aimed to explore the roles of NLR, C-reactive protein (CRP) and serum lipid levels on suicidal behavior in patients with MDD. The study group consisted of 139 inpatients diagnosed with MDD [37 suicide attempters (SA); 102 suicide non-attempters (NSA)], 50 healthy controls and matched according to age, gender and education. NLR, PLR, CRP and lipid values were obtained from digital inpatient records. CRP levels and NLR were substantially higher in patients with SA than in subjects with NSA and healthy comparison subjects after adjusting the confounding factors. The logistic regression included two predictive variables for suicide status in patients with depressive disorder (A) previous suicidal history; (B) NLR. This is the first study suggesting that NLR may be a trait marker for suicidal vulnerability via a relationship between NLR and a recent suicide attempt in depressed inpatients. Future prospective studies are needed to determine the exact roles of NLR, and other inflammatory markers on suicidality in MDD.

  14. High Neutrophil-to-Lymphocyte Ratio is a Significant Predictor of Cardiovascular and All-Cause Mortality in Patients Undergoing Peritoneal Dialysis

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    Xiangxue Lu

    2018-03-01

    Full Text Available Background/Aims: Chronic inflammation is associated with increased risk of cardiovascular death in patients with end-stage renal disease (ESRD. Although elevated neutrophil-to-lymphocyte ratio (NLR, a novel inflammatory marker, has been shown to predict cardiovascular disease and all-cause mortality in the general population, limited evidence is available for its role in ESRD. Methods: We enrolled 86 patients undergoing peritoneal dialysis (PD for a 36-month follow-up to investigate the association between the NLR and arterial stiffness markers, namely, carotid-femoral pulse wave velocity (cfPWV and carotid augmentation index (AIx, and mortality in PD patients. The primary endpoints were cardiovascular mortality and all-cause mortality. Kaplan–Meier curves were used to show the cumulative incidence of cardiovascular mortality and all-cause mortality. Results: High NLR was found to be a predictor of increased cfPWV (β = 1.150; P < 0.001 and AIx (β = 3.945; P < 0.001 in patients on PD. Patients with higher NLR had lower survival during follow-up. Kaplan–Meier curves showed that the cumulative incidences of both cardiovascular mortality and all-cause mortality were significantly higher in patients with NLR ≥ 4.5 (both P < 0.01. Conclusion: Our results suggest that high NLR is independently associated with arterial stiffness and predicts cardiovascular and all-cause mortality in PD patients.

  15. Evaluation of blood neutrophil to lymphocyte and platelet to lymphocyte ratios according to plasma glucose status and serum insulin-like growth factor 1 levels in patients with acromegaly.

    Science.gov (United States)

    Üçler, R; Aslan, M; Atmaca, M; Alay, M; Ademoğlu, E N; Gülşen, I

    2016-06-01

    Cardiovascular, respiratory, and cerebrovascular diseases and malignancies are responsible for morbidity and mortality in acromegaly. Also these diseases are associated with chronic inflammation. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are currently gaining interest as new markers of inflammation. Moreover, increased morbidity and mortality are positively correlated with the presence of diabetes and levels of insulin-like growth factor 1 (IGF-1) in acromegaly. The objective of the present study was to investigate the relationship between these markers and acromegaly according to plasma glucose status and serum IGF-1 levels. We retrospectively analyzed data from 61 acromegaly patients who were in a newly diagnosed period (35 male, 26 female; mean age 38.13 ± 13.98). Patients with normal plasma glucose (n = 27), impaired fasting glucose (n = 18), and diabetes mellitus (n = 16) were categorized into three different groups. NLR and PLR were compared between the study groups and were evaluated according to IGF-1 levels. There were no statistically significant differences in NLR and PLR measurements among the study groups (p > 0.05). However, there were significant positive correlations between NLR and IGF-1 levels and between PLR and IGF-1 levels when all patients were evaluated (r = 0.334, p = 0.011 and r = 0.277, p = 0.035, respectively). This is the first report studying the relationship of NLR and PLR with glucose status and IGF-1 levels in acromegaly patients. Our study results suggest that subclinical inflammation may play a role in increased incidence of mortality and morbidity, which depends on uncontrolled IGF-1 levels in patients with acromegaly. © The Author(s) 2015.

  16. Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts

    International Nuclear Information System (INIS)

    Shin, H.S.; Hayden, M.; Langley, S.; Kaliss, N.; Smith, M.R.

    1975-01-01

    Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were active in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls. (U.S.)

  17. Improved survival of newborns receiving leukocyte transfusions for sepsis

    International Nuclear Information System (INIS)

    Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

    1984-01-01

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions

  18. Regulation of primary cytotoxic T lymphocyte responses generated during mixed leukocyte culture with H-2d identical Qa-1-disparate cells

    International Nuclear Information System (INIS)

    Huston, D.P.; Tavana, G.; Rich, R.R.; Gressens, S.E.

    1986-01-01

    Cytotoxic lymphocyte (CTL) responses are not usually generated during primary mixed leukocyte culture (MLC) with H-2 identical cells. Thus NZB mice are unusual in that their spleen cells do mount CTL responses during primary MLC with H-2d identical stimulator cells; the predominant target antigen for these NZB responses is Qa-1b. Considering the numerous immunoregulatory defects in NZB mice, we postulated that these NZB anti-Qa-1 primary CTL responses were due to an abnormality in T suppressor cell activity. Cellular interactions capable of suppressing NZB anti-Qa-1 primary CTL responses were investigated by using one-way and two-way MLC with spleen cells from NZB mice and other H-2d strains. Although H-2d identical one-way MLC with the use of NZB responders resulted in substantial CTL responses, only minimal CTL responses were detected from two-way MLC with the use of NZB spleen cells plus nonirradiated spleen cells from other H-2d mice. Thus the presence of non-NZB spleen cells in the two-way H-2d identical MLC prevented the generation of NZB CTL. Noncytotoxic mechanisms were implicated in the suppression of the NZB CTL responses during two-way MLC, because only minimal CTL activity was generated when NZB spleen cells were cultured with semiallogeneic, H-2d identical (e.g., NZB X BALB) F1 spleen cells. The observed suppression could be abrogated with as little as 100 rad gamma-irradiation to the non-NZB spleen cells. The phenotype of these highly radiosensitive spleen cells was Thy-1+, Lyt-1+, Lyt-2-, L3T4+. The functional presence of these cells in the spleens of semiallogeneic, H-2d identical F1 mice indicated that their deficiency in NZB mice was a recessive trait. These data suggest that NZB mice lack an L3T4+ cell present in the spleens of normal mice that is capable of suppressing primary anti-Qa-1 CTL responses

  19. Leukocyte changes across menstruation, ovulation, and mid-luteal phase and association with sex hormone variation.

    Science.gov (United States)

    Nowak, Judyta; Borkowska, Barbara; Pawlowski, Boguslaw

    2016-09-10

    Total leukocyte count (white blood cells-WBC) and the count of each subpopulation vary across the menstrual cycle, but results of studies examining the time and direction of these changes are inconsistent and methodologically flawed. Besides, no previous study focused on leukocyte count on the day of ovulation. Blood samples were obtained from 37 healthy and regularly cycling women aged 19.8-36.1 years. Samples were taken three times: during menstruation (M), ovulation (O), and in the mid-luteal phase (ML). WBC, neutrophils, lymphocytes, mixed cells, progesterone (P,) and estradiol (E) were measured in each of the three target phases of the cycle. Compared to menstruation, WBC (P = 0.002) and neutrophils (P < 0.001) increased around ovulation and remained stable in the mid-luteal phase, whereas lymphocyte and mixed cell counts did not change throughout the menstrual cycle. There were some correlations of sex hormone variation with leukocyte changes between M and O (positive for E and WBC, negative for P and WBC and for P and neutrophil count; P < 0.05), but not between O and ML. Peripheral leukocyte changes taking place in the second half of the cycle are already observable on the day of ovulation and they are associated with sex hormone variation. We speculate that these changes may lead to increased immune protection against pathogens at a time when fertilization and implantation typically occur. Am. J. Hum. Biol. 28:721-728, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. The Optimal Cut-Off Value of Neutrophil-to-Lymphocyte Ratio for Predicting Prognosis in Adult Patients with Henoch–Schönlein Purpura

    Science.gov (United States)

    Park, Chan Hyuk; Han, Dong Soo; Jeong, Jae Yoon; Eun, Chang Soo; Yoo, Kyo-Sang; Jeon, Yong Cheol; Sohn, Joo Hyun

    2016-01-01

    Background The development of gastrointestinal (GI) bleeding and end-stage renal disease (ESRD) can be a concern in the management of Henoch–Schönlein purpura (HSP). We aimed to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with the prognosis of adult patients with HSP. Methods Clinical data including the NLR of adult patients with HSP were retrospectively analyzed. Patients were classified into three groups as follows: (a) simple recovery, (b) wax & wane without GI bleeding, and (c) development of GI bleeding. The optimal cut-off value was determined using a receiver operating characteristics curve and the Youden index. Results A total of 66 adult patients were enrolled. The NLR was higher in the GI bleeding group than in the simple recovery or wax & wane group (simple recovery vs. wax & wane vs. GI bleeding; median [IQR], 2.32 [1.61–3.11] vs. 3.18 [2.16–3.71] vs. 7.52 [4.91–10.23], P<0.001). For the purpose of predicting simple recovery, the optimal cut-off value of NLR was 3.18, and the sensitivity and specificity were 74.1% and 75.0%, respectively. For predicting development of GI bleeding, the optimal cut-off value was 3.90 and the sensitivity and specificity were 87.5% and 88.6%, respectively. Conclusions The NLR is useful for predicting development of GI bleeding as well as simple recovery without symptom relapse. Two different cut-off values of NLR, 3.18 for predicting an easy recovery without symptom relapse and 3.90 for predicting GI bleeding can be used in adult patients with HSP. PMID:27073884

  1. The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone

    Directory of Open Access Journals (Sweden)

    Martin Boegemann

    2017-02-01

    Full Text Available The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS and overall survival (OS was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR <5 and 17 with NLR >5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months (HR: 1.6 (95%CI:0.9–2.8; p = 0.11. After multivariate adjustment (MVA, ECOG > 0–1, baseline LDH>upper limit of normal (UNL and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months (HR: 2.3 (95%CI:1.3–4.0; p < 0.01. In MVA, ECOG > 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to <5 prognosticated worse PFS (five versus 12 months (HR: 4.1 (95%CI:1.1–15.8; p = 0.04. MVA showed a trend towards worse PFS for NLR-change to <5 (p = 0.11. NLR-change to <5 led to non-significant shorter median OS (seven versus 16 months (HR: 2.3 (95%CI:0.7–7.1; p = 0.15. MVA showed non-significant difference for OS. We concluded baseline NLR <5 is associated with improved survival. In contrast, in patients with baseline NLR >5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully.

  2. Persistent elevation of neutrophil/lymphocyte ratio associated with new onset atrial fibrillation following percutaneous coronary intervention for acute st segment elevation myocardial infarction

    International Nuclear Information System (INIS)

    Chavarria, N.; Wong, C.; Hussain, H.; Joiya, H.U.

    2015-01-01

    Increasing evidence suggests that inflammation plays an important role in initiation and maintaining of atrial fibrillation (AF). The Neutrophil to Lymphocyte (N/L) Ratio is an easily derived and readily available parameter that has emerged as marker of inflammation with predictive and prognostic value. We investigated the association between N/L ratio and incidence of atrial fibrillation in patients undergoing cardiac catheterization for acute ST-segment elevation myocardial infarction (STEMI). Methods: This cross sectional descriptive study was carried out at New York Hospital Queens. We retrospectively analysed clinical, hematologic and angiographic data of 290 patients who underwent coronary angiography with stent placement for acute ST-segment elevation myocardial infarction between 2008-2011. Results: Study cohort of 290 patients had mean age 63.3 ± 13.0 years consisting of 81.4% male. The N/L ratio was measured at time points: <6 hours pre-catheterization, <12, 48 and 96 hours post catheterization. Patients who developed AF (n=40, 13.8%), had higher post catheterization N/L ratios at 48 hours (median 5.23 vs 3.00, p=0.05) and 96 hours (median 4.67 vs 3.56, p=0.03), with no differences in the immediate pre and post procedural measurements, <6 hours pre catheterization (median 2.49 vs 2.82, p=0.467) and <12 hours post catheterization (median 5.93 vs 5.03, p=0.741) respectively. Conclusion: In conclusion, these findings support an inflammatory aetiology contributing to new onset AF following percutaneous coronary intervention for acute STEMI. Further studies are warranted to elucidate these findings. (author)

  3. High Neutrophil-to-lymphocyte Ratio as Prognostic Factor in Patients Affected by Upper Tract Urothelial Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Marchioni, Michele; Cindolo, Luca; Autorino, Riccardo; Primiceri, Giulia; Arcaniolo, Davide; De Sio, Marco; Schips, Luigi

    2017-06-01

    Given the increasing interest in the possible role of the neutrophil-to-lymphocyte ratio (NLR) as an easily available oncologic marker for upper tract urothelial cancer (UTUC), we sought to quantify the prognostic effect of this biomarker and assess its consistency in UTUC. A systematic review of the published data was performed up to May 2016 using multiple search engines (PubMed, Ovid, and Scopus) to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing patients with a high and those with a low NLR before surgical treatment of UTUC to determine whether the NLR is an independent predictor of survival. Pooled estimates were calculated using a fixed-effects model if no significant heterogeneity was identified. Alternatively, a random-effects model was used when significant heterogeneity was detected. For continuous outcomes, the weighted mean difference was used as a summary measure. For binary variables, the odds ratio or risk ratio was calculated with the 95% confidence intervals (CIs). Statistical analyses were performed using RevMan, version 5. Six studies with 1710 patients were included. A high NLR was associated with poorer oncologic outcomes in patients affected by UTUC, in particular in terms of overall survival (hazard ratio [HR], 1.97; 95% CI, 1.27-3.04; P = .002) and recurrence-free survival (HR, 1.53; 95% CI, 1.19-1.96; P = .0009) but not cancer-specific survival (HR, 1.25; 95% CI, 0.29-5.41; P = .77). Current evidence suggests that the NLR might have an independent role as a prognostic factor in patients affected by UTUC undergoing surgical treatment. The NLR potentially represents an easily available measurement of prognosis; however, it requires validation in larger prospective studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies.

    Science.gov (United States)

    Wu, Shuiqing; Zhao, Xiaokun; Wang, Yinhuai; Zhong, Zhaohui; Zhang, Lei; Cao, Jian; Ai, Kai; Xu, Ran

    2018-01-01

    Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

  5. Clinical value of the preoperative neutrophil-to-lymphocyte ratio and red blood cell distribution width in patients with colorectal carcinoma.

    Science.gov (United States)

    Han, Fuyan; Shang, Xuming; Wan, Furong; Liu, Zhanfeng; Tian, Wenjun; Wang, Dan; Liu, Yiqing; Wang, Yong; Zhang, Bingchang; Ju, Ying

    2018-03-01

    The aim of the present study was to investigate the clinical value of the preoperative neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in the peripheral blood of colorectal carcinoma (CRC) patients. Clinical data obtained from 240 patients with CRC undergoing radical surgical resection in Shandong Provincial Hospital Affiliated to Shandong University (Jinan, Shandong, China) between January 2011 and April 2015 were retrospectively analyzed. Data were also collected from 110 patients with colon polyps and 48 healthy volunteers to serve as controls for comparative analysis. The clinicopathological characteristics of the patients in the low and high NLR and RDW groups were compared. The NLR and RDW values were compared prior to and following surgery. Kaplan-Meier analyses and Cox regression modeling were performed to predict overall survival (OS) and disease-free survival (DFS). The NLR and RDW levels in the CRC patients were markedly higher than those in the colon polyp patients and the healthy controls. The optimum NLR and RDW cutoff points for CRC were 2.06 and 13.45%, respectively. Significant differences were detected in tumor location, diameter, degree of differentiation, tumor depth, carcinoembryonic antigen and carbohydrate antigen 199 when comparing the high and low NLR groups (P0.05). CRC patients with an increased RDW had significantly worse OS and DFS rates, particularly those with metastatic CRC (P<0.05). Patients with a high NLR exhibited a reduced DFS time in CRC (P=0.053), although this difference was not significant, and a significantly worse DFS time in metastatic CRC (P=0.047). In conclusion, it is convenient to use preoperative NLR and RDW to predict prognosis following surgery for patients with CRC.

  6. Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Localized and Advanced Prostate Cancer: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Tang, Lu; Li, Xintao; Wang, Baojun; Luo, Guoxiong; Gu, Liangyou; Chen, Luyao; Liu, Kan; Gao, Yu; Zhang, Xu

    2016-01-01

    Increasing evidence suggests that inflammation plays an essential role in cancer development and progression. The inflammation marker neutrophil-lymphocyte ratio (NLR) is correlated with prognosis across a wide variety of tumor types, but its prognostic value in prostate cancer (PCa) remains controversial. In the present meta-analysis, the prognostic value of NLR in PCa patients is investigated. We performed a meta-analysis to determine the predictive value of NLR for overall survival (OS), recurrence-free survival (RFS), and clinical features in patients with PCa. We systematically searched PubMed, ISI Web of Science, and Embase for relevant studies published up to October 2015. A total of 9418 patients from 18 studies were included in the meta-analysis. Elevated pretreatment NLR predicted poor OS (HR 1.628, 95% CI 1.410-1.879) and RFS (HR 1.357, 95% CI 1.126-1.636) in all patients with PCa. However, NLR was insignificantly associated with OS in the subgroup of patients with localized PCa (HR 1.439, 95% CI 0.753-2.75). Increased NLR was also significantly correlated with lymph node involvement (OR 1.616, 95% CI 1.167-2.239) but not with pathological stage (OR 0.827, 95% CI 0.637-1.074) or Gleason score (OR 0.761, 95% CI 0.555-1.044). The present meta-analysis indicated that NLR could predict the prognosis for patients with locally advanced or castration-resistant PCa. Patients with higher NLR are more likely to have poorer prognosis than those with lower NLR.

  7. Maintenance therapy of childhood acute lymphoblastic leukemia revisited-Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

    Science.gov (United States)

    Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard; Heyman, Mats; Wesenberg, Finn; Kristinsson, Jon; Vettenranta, Kim; Schrøeder, Henrik; Weinshilboum, Richard; Jensen, Katrine Lykke; Grell, Kathrine; Rosthoej, Susanne

    2016-12-01

    6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose adjustment guidelines. To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP maintenance therapy targeted to a white blood cell count (WBC) of 1.5-3.5 × 10 9 /l. After a median follow-up of 13.8 years for patients in remission, stepwise Cox regression analysis did not find age, average doses of 6MP and MTX, hemoglobin, absolute lymphocyte counts, thrombocyte counts, or Ery levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10 9 /l rise [1.00-1.09], P = 0.048), the absolute neutrophil count (ANC; HR = 1.7 per 10 9 /l rise [1.3-2.4], P = 0.0007), and Ery thiopurine methyltransferase activity (HR = 2.7 per IU/ml rise [1.1-6.7], P = 0.03). WBC was significantly related to ANC (Spearman correlation coefficient, r s  = 0.77; P best hematological target for dose adjustments of maintenance therapy. © 2016 Wiley Periodicals, Inc.

  8. Value of neutrophil-to-lymphocyte ratio for predicting lung cancer prognosis: A meta-analysis of 7,219 patients.

    Science.gov (United States)

    Yu, Yu; Qian, Lei; Cui, Jiuwei

    2017-09-01

    Current evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) may be a biomarker for poor prognosis in lung cancer, although this association remains controversial. Therefore, a meta-analysis was performed to evaluate the association between NLR and lung cancer outcome. A systematic literature search was performed through the PubMed, Embase and Cochrane Library databases (until July 30, 2016), to identify studies evaluating the association between NLR and overall survival (OS) and/or progression-free survival (PFS) among patients with lung cancer. Based on the results of this search, data from 18 studies involving 7,219 patients with lung cancer were evaluated. The pooled hazard ratio (HR) suggested that elevated pretreatment NLR predicted poor OS [HR=1.46, 95% confidence interval (CI): 1.30-1.64] and poor PFS (HR=1.42, 95% CI: 1.15-1.75) among patients with lung cancer. Subgroup analysis revealed that the prognostic value of NLR for predicting poor OS increased among patients who underwent surgery (HR=1.50, 95% CI: 1.21-1.84) or patients with early-stage disease (HR=1.64, 95% CI: 1.37-1.97). An NLR cut-off value of ≥4 significantly predicted poor OS (HR=1.56, 95% CI: 1.31-1.85) and PFS (HR=1.54, 95% CI: 1.13-1.82), particularly in the cases of small-cell lung cancer. Thus, the results of the present meta-analysis suggested that an elevated pretreatment NLR (e.g., ≥4) may be considered as a biomarker for poor prognosis in patients with lung cancer.

  9. Neutrophil to lymphocyte ratio is associated with proximal/middle segment of the LAD lesions in patients with ST segment elevation infarction

    Directory of Open Access Journals (Sweden)

    Ozlem Arican Ozluk

    2017-01-01

    Full Text Available Introduction: Neutrophil to lymphocyte ratio (NLR was revaled to have a close relation with atherosclerotic cardiovascular disease. The relationship between NLR and culprit plaque localization has never been studied. Aim of the study : To evaluate the association between NLR and unstable plaque localization of left anterior descending artery (LAD in anterior miyocardial infarction patients. Material and methods : Patients admitted to our hospital with acute anterior STEMI were included. Fifhy-eight patients who have single-vessel disease at LAD and their hematological parameters were analyzed retrospectively. Proximal segment of LAD lesions were groupped as Group I and mid segment of the LAD lesion groupped as Group II. The groups were compared according to their NLR and other parameters. Results : Between group I (n = 41, mean age 52.5 ±12.7 and group II (n = 17, mean ages 52.0 ±10.8; NLR, were significantly higher in group I compared to the group II (6.9 ±5.6 vs. 3.3 ±2.0, p = 0.01. In group I, left ventricular ejection fraction (LVEF was significantly lower (p = 0.02. In correlation analyzes, NLR was positively correlated with CK MB (r = 0.32, p = 0.01 and negatively correlated with LVEF (r = –0.28, p = 0.03. Conclusions : The present study demonstrated that anterior myocardial infarction patients with high NLR had a greater possibility having proximal culprit lesion on the LAD. Therefore NLR can be used as a useful tool to culprit plaque localization in patients with acute miyocardial infarction patients.

  10. Neutrophil-lymphocyte ratio is a novel reliable predictor of nephropathy, retinopathy, and coronary artery disease in Indians with type-2 diabetes

    Directory of Open Access Journals (Sweden)

    Sachin Chittawar

    2017-01-01

    Full Text Available Background and Aims: Neutrophil-lymphocyte ratio (NLR has been suggested to be a predictor of coronary artery disease (CAD, and end-organ damage in type-2 diabetes mellitus (T2DM. Similar data are lacking from Indians with T2DM. Hence, this study aimed to evaluate the role of NLR as a predictor of microvascular complications and CAD in T2DM. Subjects and Methods: Consecutive T2DM patients attending the outpatient services of 2 different hospitals, who gave consent, underwent clinical, anthropometric evaluation, and evaluation for the occurrence of retinopathy, nephropathy, neuropathy, and CAD. Results: A total of 298 patients were screened of which 265 patients' data were analyzed. Occurrence of hypertension, neuropathy, nephropathy, retinopathy, and CAD was 12.8%, 18.5%, 41.5%, 62.3%, and 3.8%, respectively. Patients in higher NLR quartiles had significantly higher diabetes duration, occurrence of nephropathy, albuminuria, retinopathy, CAD and lpwer glomerular filtration rate. Patients with more microvascular complications had significantly longer diabetes duration, blood pressure, NLR, creatinine, and urine albumin excretion. Binary logistic regression revealed NLR followed by body mass index were best predictors of microvascular complications. NLR had areas under the receiver operating characteristic curve (AUC of 0.888 (95% CI: 0.848–0.929; P < 0.001, 0.708 (95% CI: 0.646–0.771; P < 0.001, and 0.768 (95% CI: 0.599–938; P = 0.004 in predicting albuminuria, retinopathy, and CAD, respectively. NLR of 2.00 had sensitivity and specificity of 86.4% and 69% in predicting albuminuria; sensitivity and specificity of 64.2% and 63% in predicting retinopathy; sensitivity and specificity of 80% and 47.1% in predicting CAD. Conclusion: NLR is inexpensive, easy to use, reliable predictor of nephropathy, retinopathy, and CAD in Indian T2DM.

  11. Detection of effect cytotoxic of the alpha hemolysin of E. Coli (HLY A) in leukocytes polymorphonuclear neutrophils by means of cytometry of flow

    International Nuclear Information System (INIS)

    Garcia, J.

    2000-01-01

    Cell viability of Hly A exposed polymorphonuclear neutrophils (PMN) was assessed by propidium uptake, measured by flow cytometry. Hemolytic supernatant, but not the non hemolytic controls, caused a dose-dependent fluorescence signal in PMN. Cells exposed to low hemolytic activities (bellow 0.5 HU50/ml) did not fluoresce, although cell size, estimate by Forward Scatter (FSC), increased slightly, and returned to normal within 30-60 minutes suggesting both membrane damage in absence of propodium uptake and term cell recovery from the effects of Hly A. The fluorescent signal from permeated PMN decrease 15 minutes after exposure to Hly a, a decrease which was prevented by chelation ok extracellular Ca +2 with EGTA. Whereas Ca +2 entry into the cell is responsible for triggering mechanisms leading to loss of fluorescence, low or chelated extracelular Ca +2 facilitate propidium uptake, but the fluorescent signal does not decrease only when both intracellular and extracellular Ca +2 are chelated. The findings of this study, together whit data from other authors, are taken as basis to formulate a hypothetical sequence of events to explain the cytometric data obtained from Hly A exposed PMN, including the significance of increases in cell size without propidium uptake. (Author) [es

  12. The Effect of Hemiscorpius lepturus (Scorpionida: Hemiscorpiidae Venom on Leukocytes and the Leukocyte Subgroups in Peripheral Blood of Rat

    Directory of Open Access Journals (Sweden)

    Mehri Ghafourian

    2016-01-01

    Full Text Available Background: The aim of this study was to investigate the effect of Hemiscorpius lepturus venom on leukocytes and the leukocyte subgroups in peripheral blood of rat.Methods: In this experimental study, sixty N-Mari rats were divided into three groups of 20 rats. Then the rats in each group were divided into four subgroups based on the blood sampling time that was 2, 6, 24 and 48 hours after the venom injection, respectively. The control group did not receive anything, however, the first and the second ex­perimental groups received 0.1 and 0.01mg/kg of venom, subcutaneously. In accordance with a designated four sam­pling times, the blood sampling was carried out in three groups. After RBC lysis, the leukocytes and leukocyte sub­populations were determined and counted using appropriate hematological standard methods.Results: The leukocyte and the neutrophil count at two (P<0.05, six (P<0.01 and 24 (P<0.05 hours after the venom injection showed a significant decline compared with the control group, this decrease was significant at the dose of 0.1 mg/kg until 48 hours after the venom injection (P<0.05. The lymphocyte count showed a significant decline throughout the all hours of the experiment, compared with the control group (P<0.05.Conclusion: Leukocytes are probably affected by the cytotoxicity effect of the H. lepturus venom in a dose-dependent manner. This could be a wakeup call for the medical staff to perform quick and accurate treatment in the least time possible.

  13. Assessment of the efficiency of Brentuximab Vedotin in patients with pulmonary Hodgkin Lymphoma by the mean of neutrophil to lymphocyte ratio

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    Gokhan Erdem

    2018-04-01

    Full Text Available Background: Lung involvement, an uncommon initial presentation of Hodgkin Lymphoma (HL, may appear as primary or secondary pulmonary HL. Although the combination of Brentuximab vedotin (BV with AVD is suggested as an alternative treatment to combinations including bleomycin for patients with pulmonary involvement. The efficacy and adverse effects of BV have not been specialized on pulmonary HL. There is insufficient data about neutrophil to lymphocyte ratio (NLR of cases treated with BV. We performed this retrospective study to evaluate the efficacy and toxicity of BV in patients with pulmonary HL and to demonstrate the prognostic role of NLR in patients treated with BV. Methods: Data of 10 CD 30 (+ HL patients who treated with BV between years 2011–2016 were analyzed retrospectively. Relapsed cases after autologous bone marrow transplantation (ABMT and/or resistant cases to at least two lines of chemotherapy, and treated with BV were included in the study. Results: Patients underwent a median of 8.5 cycles BV. Eight patients (80% achieved an objective response including 2 of them (20% with complete response and six of them (60% with a partial response at the end of the 3rd cycle. At a median follow-up of 16.8 months, median progression-free survival for all patients was 6 months and 3 patients died because of progression. BV, as a single agent, revealed well response in HL cases with pulmonary involvement and other clinical types. No pulmonary toxicity has been occurred due to BV. NLR was found to be o good indicator of prognosis and mortality in pulmonary HL patients and other HL patients. While NLR was not influenced by BV, it can be suggested as an easy prognostic marker in patients treated with BV. Conclusion: BV may be used as a bridge therapy to the next curative treatment in order to obtain minimal tumor burden in pulmonary HL patients, and NLR can be used as a prognostic marker in these patients. We believe that this study contributes

  14. CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera

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    Bettinotti Maria

    2004-03-01

    Full Text Available Abstract Genes in the Leukocyte Antigen 6 (Ly-6 superfamily encode glycosyl-phosphatidylinositol (GPI anchored glycoproteins (gp with conserved domains of 70 to 100 amino acids and 8 to 10 cysteine residues. Murine Ly-6 genes encode important lymphocyte and hematopoietic stem cell antigens. Recently, a new member of the human Ly-6 gene superfamily has been described, CD177. CD177 is polymorphic and has at least two alleles, PRV-1 and NB1. CD177 was first described as PRV-1, a gene that is overexpressed in neutrophils from approximately 95% of patients with polycythemia vera and from about half of patients with essential thrombocythemia. CD177 encodes NB1 gp, a 58–64 kD GPI gp that is expressed by neutrophils and neutrophil precursors. NB1 gp carries Human Neutrophil Antigen (HNA-2a. Investigators working to identify the gene encoding NB1 gp called the CD177 allele they described NB1. NB1 gp is unusual in that neutrophils from some healthy people lack the NB1 gp completely and in most people NB1 gp is expressed by a subpopulation of neutrophils. The function of NB1 gp and the role of CD177 in the pathogenesis and clinical course of polycythemia vera and essential thrombocythemia are not yet known. However, measuring neutrophil CD177 mRNA levels has become an important marker for diagnosing the myeloproliferative disorders polycythemia vera and essential thrombocythemia.

  15. Neutrophil heterogeneity: implications for homeostasis and pathogenesis

    NARCIS (Netherlands)

    Silvestre-Roig, Carlos; Hidalgo, Andres; Soehnlein, Oliver

    2016-01-01

    Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a

  16. Using milk leukocyte differentials for diagnosis of subclinical bovine mastitis.

    Science.gov (United States)

    Gonçalves, Juliano Leonel; Lyman, Roberta L; Hockett, Mitchell; Rodriguez, Rudy; Dos Santos, Marcos Veiga; Anderson, Kevin L

    2017-08-01

    This research study aimed to evaluate the use of the milk leukocyte differential (MLD) to: (a) identify quarter milks that are culture-positive; and (b) characterize the milk leukocyte responses to specific groups of pathogens causing subclinical mastitis. The MLD measures the absolute number and relative percentage of inflammatory cells in milk samples. Using the MLD in two dairy herds (170 and 172 lactating cows, respectively), we studied all lactating cows with a most recent monthly Dairy Herd Improvement Association somatic cell count (SCC) >200 × 103 cells/ml. Quarter milk samples from 78 cows meeting study criteria were analysed by MLD and aseptically collected milk samples were subjected to microbiological culture (MC). Based upon automated instrument evaluation of the number and percentage of inflammatory cells in milk, samples were designated as either MLD-positive or - negative for subclinicial mastitis. Positive MC were obtained from 102/156 (65·4%) of MLD-positive milk samples, and 28/135 (20·7%) of MLD-negative milk samples were MC-positive. When MC was considered the gold standard for mastitis diagnosis, the calculated diagnostic Se of the MLD was 65·4% (IC95% = 57·4 to 72·8%) and the Sp was 79·3% (IC95% = 71·4 to 85·7%). Quarter milks positive on MC had higher absolute numbers of neutrophils, lymphocytes and macrophages, with higher neutrophils% and lymphocytes% but lower macrophages%. The Log10 (N/L) ratios were the most useful ratio to differentiate specific subclinical mastitis quarters from healthy quarters. Use of the MLD on cows with monthly composite SCC > 200 × 103 cells/ml for screening at quarter level identified quarters more likely to be culture-positive. In conclusion, the MLD can provide an analysis of mammary quarter status more detailed than provided by SCC alone; however, the MLD response to subclinical mastitis was not found useful to specifically identify the causative pathogen.

  17. The Application of Dextran Sedimentation as an Initial Step in Neutrophil Purification Promotes Their Stimulation, due to the Presence of Monocytes

    Science.gov (United States)

    Ferrante, Antonio

    2017-01-01

    The purification of human neutrophils for in vitro studies is challenging as they are easily activated through ex vivo manipulations. The technique of erythrocyte sedimentation combined with density gradient centrifugation remains widely practiced and was the subject of this study. Since in the sedimentation step the leukocytes are incubated with dextran, we have raised the likelihood that cellular activation would occur with mediator release leading to neutrophil activation. By comparing the activity of neutrophils purified from whole blood by the classical 2-step method of dextran sedimentation followed by low-density Ficoll-Hypaque (1.077 g/mL) medium, and the 1-step high-density Ficoll-Hypaque (1.114 g/mL) gradient centrifugation, we found that neutrophils from the 2-step method had a significant increase in cell surface CD11b expression and CD62L shedding and a marked increase in adhesion. Decreased random migration and chemotaxis and raised baseline oxidative burst activity were also observed. The effect was not specific to dextran, as using Ficoll for erythrocyte sedimentation replicated the elevated neutrophil adherence. Through the depletion of monocytes, lymphocytes, and platelets prior to sedimentation, we deduced that monocytes were responsible for the neutrophil activation. Our findings suggest that care needs to be exercised in choosing the method of neutrophil purification for functional studies. PMID:29164154

  18. Association of peripheral total and differential leukocyte counts with obesity-related complications in young adults.

    Science.gov (United States)

    Yoshimura, Aya; Ohnishi, Shunsuke; Orito, Chieko; Kawahara, Yukako; Takasaki, Hiroyo; Takeda, Hiroshi; Sakamoto, Naoya; Hashino, Satoshi

    2015-01-01

    Obesity has been demonstrated to be associated with elevated leukocytes in adults and children. This study assessed the associations between peripheral total and differential leukocyte counts and obesity-related complications in young adults. 12 obese (median age 21.5 (range 19-28) years, median BMI 35.7 (range 32.0-44.9) kg/m(2)) and 11 normal (median age 23 (range 18-27) years, median BMI 19.5 (range 18.1-21.7) kg/m(2)) adults were enrolled. Complete blood count and serum levels of liver enzymes, fasting blood glucose, insulin and lipids were measured, and the homeostasis model assessment of insulin resistance was calculated. Fat mass was calculated using a bioimpedance analysis device, and ultrasonography was performed to measure fat thickness and to detect fatty change of the liver. Total leukocyte and monocyte counts were significantly increased in obese young adults. Total leukocyte count was associated with liver enzyme levels, insulin resistance as well as visceral and subcutaneous fat thickness. Neutrophil count was associated with insulin resistance. Lymphocyte count was associated with serum liver enzymes, insulin resistance, and dyslipidemia. Monocyte count was associated with serum liver enzyme, insulin resistance, visceral and subcutaneous fat thickness, body fat mass, and percentage body fat. The results of this study suggest that chronic low-grade systemic inflammation is associated with obesity-related complications such as nonalcoholic fatty liver disease, insulin resistance, and dyslipidemia in young adults. © 2015 S. Karger GmbH, Freiburg.

  19. Tenocytes, pro-inflammatory cytokines and leukocytes: a relationship?

    OpenAIRE

    Al-Sadi, Onays; Schulze-Tanzil, Gundula; Kohl, Benjamin; Lohan, Anke; Lemke, Marion; Ertel, Wolfgang; John, Thilo

    2012-01-01

    Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures.

  20. Social Regulation of Leukocyte Homeostasis: The Role of Glucocorticoid Sensitivity

    Science.gov (United States)

    Cole, Steve W.

    2010-01-01

    Recent small-scale genomics analyses suggest that physiologic regulation of pro-inflammatory gene expression by endogenous glucocorticoids may be compromised in individuals who experience chronic social isolation. This could potentially contribute to the elevated prevalence of inflammation-related disease previously observed in social isolates. The present study assessed the relationship between leukocyte distributional sensitivity to glucocorticoid regulation and subjective social isolation in a large population-based sample of older adults. Initial analyses confirmed that circulating neutrophil percentages were elevated, and circulating lymphocyte and monocyte percentages were suppressed, in direct proportion to circulating cortisol levels. However, leukocyte distributional sensitivity to endogenous glucocorticoids was abrogated in individuals reporting either occasional or frequent experiences of subjective social isolation. This finding held in both nonparametric univariate analyses and in multivariate linear models controlling for a variety of biological, social, behavioral, and psychological confounders. The present results suggest that social factors may alter immune cell sensitivity to physiologic regulation by the hypothalamic-pituitary-adrenal axis in ways that could ultimately contribute to the increased physical health risks associated with social isolation. PMID:18394861

  1. Neutrophils in Cancer: Two Sides of the Same Coin.

    Science.gov (United States)

    Uribe-Querol, Eileen; Rosales, Carlos

    2015-01-01

    Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

  2. Neutrophils in Cancer: Two Sides of the Same Coin

    Directory of Open Access Journals (Sweden)

    Eileen Uribe-Querol

    2015-01-01

    Full Text Available Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

  3. PHYSIOLOGICAL AND LEUKOCYTE SUBSET RESPONSES TO EXERCISE AND COLD EXPOSURE IN COLD-ACCLIMATIZED SKATERS

    Directory of Open Access Journals (Sweden)

    K. Kim

    2014-07-01

    Full Text Available We investigated physiological responses and changes in circulating immune cells following exercise in cold and thermoneutral conditions. Participants were short track skaters (n=9 who were acclimatized to cold conditions, and inline skaters (n=10 who were not acclimatized. All skaters were young, and skating at a recreational level three days per week for at least one year. Using a cross-over design, study variables were measured during 60 min of submaximal cycling (65% ·VO2max in cold (ambient temperature: 5±1°C, relative humidity: 41±9% and thermoneutral conditions (ambient temperature: 21±1°C, relative humidity: 35±5%. Heart rate, blood lactate and tympanic temperature were measured at rest, during exercise and recovery. Plasma cortisol, calprotectin and circulating blood cell numbers were measured before and after 60 min of cold or thermoneutral conditions, and during recovery from exercise. Heart rate was lower in both groups during exercise in cold versus thermoneutral conditions (P<0.05. The increase in total leukocytes during recovery was primarily due to an increase in neutrophils in both groups. The cold-acclimatized group activated neutrophils after exercise in cold exposure, whereas the non-acclimatized group activated lymphocyte and cortisol after exercise in cold exposure. Lymphocyte subsets significantly changed in both groups over time during recovery as compared to rest. Immediately after exercise in both groups, CD16+ and CD69+ cells were elevated compared to rest or before exercise in both conditions. Acclimatization to exercise in the cold does not appear to influence exercise-induced immune changes in cold conditions, with the possible exception of neutrophils, lymphocytes and cortisol concentration.

  4. Prognostic impact of leukocyte counts before and during radiotherapy for oropharyngeal cancer

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    Garrett L. Jensen

    2017-12-01

    Full Text Available Introduction: Peripheral blood count components are accessible and evidently predictive in other cancers but have not been explored in oropharyngeal carcinoma. We examine if there is an association between the use of intensity-modulated radiotherapy (IMRT or intensity-modulated proton therapy (IMPT and lymphopenia, as well as if there is an association between baseline neutrophilia, baseline leukocytosis and lymphocyte nadir in oropharyngeal cancer. Materials and Methods: Analysis started with 150 patients from a previous case to case study design, which retrospectively identified adults with oropharyngeal carcinoma, 100 treated with IMRT in 2010-2012 and 50 treated with IMPT in 2011–2014. Pretreatment leukocyte, neutrophil, lymphocyte, and hemoglobin levels were extracted, as were neutrophil and lymphocyte nadir levels during radiotherapy. We retained 137 patients with recorded pre-treatment leukocyte and neutrophil levels for associated analysis and 114 patients with recorded lymphocyte levels during radiation and associated analysis. Multivariate survival analyses were done with Cox regression. Results: The radiotherapy type (IMRT vs. IMPT was not associated with lymphopenia (grade 3 P > .99; grade 4 P = .55. In univariate analyses, poor overall survival was associated with pretreatment neutrophilia (hazard ratio [HR] 5.58, 95% confidence interval [CI] 1.99–15.7, P = .001, pretreatment leukocytosis (HR 4.85, 95% CI 1.73–13.6, P = .003, grade 4 lymphopenia during radiotherapy (HR 3.28, 95% CI 1.14–9.44, P = .03, and possibly smoking status >10 pack-years (HR 2.88, 95% CI 1.01–8.18, P = .05, but only T status was possibly significant in multivariate analysis (HR 2.64, 95% CI 0.99–7.00, P = .05. Poor progression-free survival was associated with pretreatment leukocytosis and T status in univariate analysis, and pretreatment neutrophilia and

  5. Neutrophil-to-lymphocyte Ratio, Platelet-to-lymphocyte Ratio, and C-reactive Protein as New and Simple Prognostic Factors in Patients With Metastatic Renal Cell Cancer Treated With Tyrosine Kinase Inhibitors: A Systemic Review and Meta-analysis.

    Science.gov (United States)

    Semeniuk-Wojtaś, Aleksandra; Lubas, Arkadiusz; Stec, Rafał; Syryło, Tomasz; Niemczyk, Stanisław; Szczylik, Cezary

    2018-02-02

    Inflammation plays a crucial role in cancer development. In this study, we evaluate the prognostic values of systemic inflammation markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) for the progression-free survival and overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. PubMed and the Cochrane Library databases were searched for published studies on the effect of NLR, PLR, and CRP in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. In the meta-analysis, NLR (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.27-3.18; P = .003) and PLR (HR, 6.96; 95% CI, 5.04-9.62; P < .001) had a significant influence on progression-free survival, whereas all considered proinflammatory markers had a significant impact on overall survival: NLR (HR, 2.14; 95% CI, 1.67-2.73; P < .001), PLR (HR, 14.67; 95% CI, 11.10-19.57; P < .001), and CRP (HR, 1.96; 95% CI, 1.26-3.05; P = .003). Inflammation markers such as NLR, PLR, and CRP are predictors of clinical outcome and could provide additional information to individualize treatment. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Neutrophils in atherosclerosis. A brief overview

    NARCIS (Netherlands)

    Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O.

    2015-01-01

    Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was

  7. RUSSIAN EXPERIENCE WITH USING MONOCLONAL ANTIBODIES TO B-LYMPHOCYTES (RITUXIMAB IN SYSTEMIC VASCULITIDES ASSOCIATED WITH NEUTROPHIL CYTOPLASMIC ANTIBODIES (PRELIMINARY RESULTS OF THE RUSSIAN REGISTER NORMA

    Directory of Open Access Journals (Sweden)

    T. V. Beketova

    2014-01-01

    Full Text Available In 2013, Russia registered officially the indications for the use of monoclonal antibodies to B-lymphocytes (rituximab, RTM in systemic vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA-SV. This communication presents the preliminary results of the Russian register of the RTM application in autoimmune diseases (NORMA that has included 50 patients with ANCA-SV treated in 14 cities of the Russian Federation. Twenty-five of 50 (50% patients received repeated courses of RTM. RTM has demonstrated a high efficacy and a good profile of treatment safety in patients with ANCA-SV in real-life national clinical practice. Among 25 patients who had been followed up for over 12 months, the remission was achieved in 92% of cases, a decrease in the ANCA-SV activity was observed in 8%. The efficacy of RTM increased when performing repeated courses, while it has been noted that the positive results can be obtained by prescribing a repeated course of RTM at a reduced dose (500–1000 mg. Prescription of the repeated courses was primarily required in patients with granulomatosis and polyangiitis affecting the lungs. Care should be taken when combining RTM treatment with cytostatics (primarily with cyclophosphamide because of the risk of secondary immunodeficiency and infectious adverse events (AE, which have been the most frequent serious AE (12% in patients with ANCA-SV.

  8. Platelet activation and platelet-leukocyte interaction in β-thalassemia/hemoglobin E patients with marked nucleated erythrocytosis.

    Science.gov (United States)

    Keawvichit, Rassamon; Khowawisetsut, Ladawan; Chaichompoo, Porntip; Polsrila, Korakot; Sukklad, Suchana; Sukapirom, Kasama; Khuhapinant, Archrob; Fucharoen, Suthat; Pattanapanyasat, Kovit

    2012-11-01

    Patients with thalassemia, an inherited hemolytic anemia, have increased risk of hypercoagulable complications. A whole blood flow cytometric (FCM) method has been used for studies of platelet activation and platelet-leukocyte aggregation in these patients. However, this FCM method presents technical difficulties because of the high proportion of immature red blood cells (RBCs) in these patients. A protocol for the simultaneous measurement of platelet activation and their aggregation with leukocyte populations in whole blood using four-color FCM which excluded immature RBC was devised, and evaluated for the evaluation of platelet function in patients with β-thalassemia/hemoglobin E (HbE). Whole blood from these patients and from healthy volunteers was stained for platelet activation and platelet-leukocyte aggregates using anti-CD42a, anti-CD62P, anti-CD45 and glycophorin A (GPA) conjugated with different fluorochromes. Our FCM method is simple, effective and based on the assumption that GPA is present on all immature RBCs, but is not expressed on CD45⁺ leukocytes. Results from the studies showed that blood samples from these patients contained a high frequency of circulating activated platelets (CD42a⁺/CD62P⁺) when compared to samples from healthy individuals. The percentage of platelet-neutrophil, platelet-monocyte-but not platelet-lymphocyte-aggregates were also elevated in both thalassemia genotypes with marked increase in patients who had undergone splenectomy. These findings suggest that platelets adhere to neutrophils and monocytes are activated which support the clinical observation that splenectomized thalassemia patients have an increased risk of arterial or venous thrombotic manifestations.

  9. Neutrophil Lymphocyte Ratio as a predictor of systemic inflammation - A cross-sectional study in a pre-admission setting. [v1; ref status: indexed, http://f1000r.es/5cy

    Directory of Open Access Journals (Sweden)

    Lashmi Venkatraghavan

    2015-05-01

    Full Text Available Background: Neutrophil:lymphocyte ratio (NLR  is an emerging biomarker that is used to predict postoperative mortality and morbidity in cardiac and cancer surgeries. The association of this biomarker with systemic illness and its usefulness in risk assessment of preoperative patients has not been fully elucidated. Objectives: To determine the prevalence of elevated NLR in preoperative patients and to examine the relationship between elevated NLR and the presence of systemic illnesses as well as anaesthesia risk indices such as American Society of Anesthesia (ASA and the revised cardiac risk index (RCRI scores.  Design: Cross-sectional study Setting: Anaesthesia pre-admission clinic, Toronto Western Hospital, Toronto, Canada Patients: We evaluated 1117 pre-operative patients seen at an anesthesia preadmission clinic. Results: NLR was elevated (>3.3 in 26.6% of target population. In multivariate analysis, congestive cardiac failure, diabetes mellitus and malignancy were independent risk factors predicting raised NLR. After regression analysis, a relationship between NLR and ASA score (Odds Ratio 1.78; 95% CI: 1.42-2.24 and revised cardiac risk index (RCRI, odds ratio 1.33; 95% CI: 1.09-1.64, p-value: 0.0063 was observed. Conclusions:  NLR was elevated (> 3.3 in 26.6% of patients. Congestive cardiac failure and malignancy were two constant predictors of elevated NLR at >3.3 and > 4.5. There was a strong association between NLR and anesthesia risk scoring tools of ASA and RCRI.

  10. Prognostic Significance of Combination of Preoperative Platelet Count and Neutrophil-Lymphocyte Ratio (COP-NLR in Patients with Non-Small Cell Lung Cancer: Based on a Large Cohort Study.

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    Hua Zhang

    Full Text Available The aim of this study was to investigate the prognostic significance of the combination of the preoperative platelet count and neutrophil-lymphocyte ratio (COP-NLR for predicting postoperative survival of patients undergoing complete resection for non-small cell lung cancer (NSCLC.The preoperative COP-NLR was calculated on the basis of data obtained.Patients with both an increased platelet count (>30.0 × 104 mm(-3 and an elevated NLR (>2.3 were assigned a score of 2, and patients with one or neither were assigned as a score of 1 or 0, respectively.A total of 1238 NSCLC patients were enrolled in this analysis. Multivariate analysis using the 15 clinicolaboratory variables selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for DFS (HR: 1.834, 95%CI: 1.536 to 2.200, P<0.001 and OS (HR: 1.810, 95%CI: 1.587 to 2.056, P<0.001. In sub-analyses by tumor stage (I, II, IIIA, a significant association was found between DFS and OS and level of COP-NLR in each subgroup (P<0.001, P=0.002, P<0.001 for DFS, respectively; P<0.001, P=0.001, P<0.001 for OS. When the subgroup of patients with high-risk COP-NLR (score of 2 was analyzed, no benefit of adjuvant chemotherapy could be found (P=0.237 for DFS and P=0.165 for OS.The preoperative COP-NLR is able to predict the prognosis of patients with NSCLC and divide these patients into three independent groups before surgery. Our results also demonstrate that high-risk patients based on the COP-NLR do not benefit from adjuvant chemotherapy. Independent validation of our findings is warranted.

  11. Comparison of neutrophil-to-lymphocyte ratio and mean platelet volume in the prediction of adverse events after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction.

    Science.gov (United States)

    Machado, Guilherme Pinheiro; Araujo, Gustavo Neves de; Carpes, Christian Kunde; Lech, Mateus; Mariani, Stefani; Valle, Felipe Homem; Bergoli, Luiz Carlos Corsetti; Gonçalves, Sandro Cadaval; Wainstein, Rodrigo V; Wainstein, Marco V

    2018-07-01

    Elevated neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) are indirect inflammatory markers. There is some evidence that both are associated with worse outcomes in ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). The aim of the present study was to compare the capacity of NLR and MPV to predict adverse events after primary PCI. In a prospective cohort study, 625 consecutive patients with STEMI, who underwent primary PCI, were followed. Receiver operating characteristic (ROC) curve analysis was performed to calculate the area under the curve (AUC) for the occurrence of procedural complications, mortality and major adverse cardiovascular events (MACE). Mean age was 60.7 (±12.1) years, 67.5% were male. The median of NLR was 6.17 (3.8-9.4) and MPV was 10.7 (10.0-11.3). In multivariate analysis, both NLR and MPV remained independent predictors of no-reflow (relative risk [RR] = 2.26; 95%confidence interval [95%CI] = 1.16-4.32; p = 0.01 and RR = 2.68; 95%CI = 1.40-5.10; p  0.05). NLR had an excellent negative predictive value (NPV) of 96.7 for no-reflow and 89.0 for in-hospital MACE. Despite no difference in the ROC curve comparison with MPV, only NLR remained an independent predictor for in-hospital MACE. A low NLR has an excellent NPV for no-reflow and in-hospital MACE, and this could be of clinical relevance in the management of low-risk patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Inflammation, leukocytes and menstruation.

    Science.gov (United States)

    Evans, Jemma; Salamonsen, Lois A

    2012-12-01

    Menstruation has many of the features of an inflammatory process. The complexity and sequence of inflammatory-type events leading to the final tissue breakdown and bleeding are slowly being unravelled. Progesterone has anti-inflammatory properties, and its rapidly declining levels (along with those of estrogen) in the late secretory phase of each non-conception cycle, initiates a sequence of interdependent events of an inflammatory nature involving local inter-cellular interactions within the endometrium. Intracellular responses to loss of progesterone (in decidualized stromal, vascular and epithelial cells) lead to decreased prostaglandin metabolism and loss of protection from reactive oxygen species (ROS). Increased ROS results in release of NFκB from suppression with activation of target gene transcription and increased synthesis of pro-inflammatory prostaglandins, cytokines, chemokines and matrix metalloproteinases (MMP). The resultant leukocyte recruitment, with changing phenotypes and activation, provide further degradative enzymes and MMP activators, which together with a hypoxic environment induced by prostaglandin actions, lead to the tissue breakdown and bleeding characteristic of menstruation. In parallel, at sites where shedding is complete, microenvironmentally-induced changes in phenotypes of neutrophils and macrophages from pro- to anti-inflammatory, in addition to induction of growth factors, contribute to the very rapid re-epithelialization and restoration of tissue integrity.

  13. Production and characterization of monoclonal antibodies against mink leukocytes

    DEFF Research Database (Denmark)

    Chen, W.S.; Pedersen, Mikael; Gram-Nielsen, S.

    1997-01-01

    Three monoclonal antibodies (mAbs) were generated against mink leukocytes. One antibody reacted with all T lymphocytes, one with all monocytes and one had platelet reactivity. Under reducing conditions, the T lymphocyte reactive antibody immunoprecipitated 18 kDa, 23 kDa, 25 kDa and 32-40 kDa pol...

  14. Neutrophils in traumatic brain injury (TBI): friend or foe?

    Science.gov (United States)

    Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

    2018-05-17

    Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

  15. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    Science.gov (United States)

    Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lúcia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Corrêa-Oliveira, Rodrigo; Teixeira-Carvalho, Andréa

    2013-01-01

    Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. PMID:23401741

  16. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    Directory of Open Access Journals (Sweden)

    Denise Silveira-Lemos

    2013-01-01

    Full Text Available Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group before and after praziquantel treatment (ACT-TR group. Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA, increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis.

  17. Rescue from acute neuroinflammation by pharmacological chemokine-mediated deviation of leukocytes

    Directory of Open Access Journals (Sweden)

    Berghmans Nele

    2012-10-01

    Full Text Available Abstract Background Neutrophil influx is an important sign of hyperacute neuroinflammation, whereas the entry of activated lymphocytes into the brain parenchyma is a hallmark of chronic inflammatory processes, as observed in multiple sclerosis (MS and its animal models of experimental autoimmune encephalomyelitis (EAE. Clinically approved or experimental therapies for neuroinflammation act by blocking leukocyte penetration of the blood brain barrier. However, in view of unsatisfactory results and severe side effects, complementary therapies are needed. We have examined the effect of chlorite-oxidized oxyamylose (COAM, a potent antiviral polycarboxylic acid on EAE. Methods EAE was induced in SJL/J mice by immunization with spinal cord homogenate (SCH or in IFN-γ-deficient BALB/c (KO mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Mice were treated intraperitoneally (i.p. with COAM or saline at different time points after immunization. Clinical disease and histopathology were compared between both groups. IFN expression was analyzed in COAM-treated MEF cell cultures and in sera and peritoneal fluids of COAM-treated animals by quantitative PCR, ELISA and a bioassay on L929 cells. Populations of immune cell subsets in the periphery and the central nervous system (CNS were quantified at different stages of disease development by flow cytometry and differential cell count analysis. Expression levels of selected chemokine genes in the CNS were determined by quantitative PCR. Results We discovered that COAM (2 mg i.p. per mouse on days 0 and 7 protects significantly against hyperacute SCH-induced EAE in SJL/J mice and MOG35-55-induced EAE in IFN-γ KO mice. COAM deviated leukocyte trafficking from the CNS into the periphery. In the CNS, COAM reduced four-fold the expression levels of the neutrophil CXC chemokines KC/CXCL1 and MIP-2/CXCL2. Whereas the effects of COAM on circulating blood and splenic leukocytes were limited, significant

  18. Neutrophilic dermatoses in a patient with collagenous colitis

    OpenAIRE

    Didac Barco; Maria A. Barnadas; Esther Roé; Francisco J. Sancho; Elena Ricart; Agustín Alomar

    2010-01-01

    We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate...

  19. Dynamic interactions of neutrophils and biofilms

    Directory of Open Access Journals (Sweden)

    Josefine Hirschfeld

    2014-12-01

    Full Text Available Background: The majority of microbial infections in humans are biofilm-associated and difficult to treat, as biofilms are highly resistant to antimicrobial agents and protect themselves from external threats in various ways. Biofilms are tenaciously attached to surfaces and impede the ability of host defense molecules and cells to penetrate them. On the other hand, some biofilms are beneficial for the host and contain protective microorganisms. Microbes in biofilms express pathogen-associated molecular patterns and epitopes that can be recognized by innate immune cells and opsonins, leading to activation of neutrophils and other leukocytes. Neutrophils are part of the first line of defense and have multiple antimicrobial strategies allowing them to attack pathogenic biofilms. Objective/design: In this paper, interaction modes of neutrophils with biofilms are reviewed. Antimicrobial strategies of neutrophils and the counteractions of the biofilm communities, with special attention to oral biofilms, are presented. Moreover, possible adverse effects of neutrophil activity and their biofilm-promoting side effects are discussed. Results/conclusion: Biofilms are partially, but not entirely, protected against neutrophil assault, which include the processes of phagocytosis, degranulation, and formation of neutrophil extracellular traps. However, virulence factors of microorganisms, microbial composition, and properties of the extracellular matrix determine whether a biofilm and subsequent microbial spread can be controlled by neutrophils and other host defense factors. Besides, neutrophils may inadvertently contribute to the physical and ecological stability of biofilms by promoting selection of more resistant strains. Moreover, neutrophil enzymes can degrade collagen and other proteins and, as a result, cause harm to the host tissues. These parameters could be crucial factors in the onset of periodontal inflammation and the subsequent tissue breakdown.

  20. Evaluation of indium-111-2-mercaptopyridine-N-oxide for labeling leukocytes in plasma: a kit preparation

    International Nuclear Information System (INIS)

    Thakur, M.L.; McKenney, S.L.; Park, C.H.

    1985-01-01

    Pure neutrophils, lymphocytes, and mixed leukocytes have been labeled in vitro with 111 In chelated to a nontoxic, water soluble agent 2-mercaptopyridine-N-oxide (Merc). Cells were labeled in isotonic salt-balanced medium with preformed [ 111 In]Merc, or in 0.5 ml autologous plasma by incubation with dry Merc first and then with 111 In. The latter method facilitated a kit procedure that required 2 μg dry Merc when acid citrate dextrose was used as anticoagulant or 20μg when heparin was used. Labeling efficiency was dependent on cell concentration and pH. Labeled cells accumulated avidly in experimental abscesses. In dogs, the liver uptake of labeled cells was only 18.8% compared to that of 48.5% when cells were labeled with [ 111 In] oxine

  1. Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

    Directory of Open Access Journals (Sweden)

    Barja-Fidalgo C.

    2005-01-01

    Full Text Available Extracellular matrix proteins and cell adhesion receptors (integrins play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

  2. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... systemic diseases (hypertension, type 2 diabetes mellitus),. Original Article. INTRODUCTION. Postoperative ... vertigo, etc.) have been shown.[3-15]. In this study, we aimed to investigate possible relationship between preoperative NLR and postoperative pain (which was evaluated by analgesic demand at.

  3. Leukocyte adhesion deficiencies

    NARCIS (Netherlands)

    van de Vijver, Edith; van den Berg, Timo K.; Kuijpers, Taco W.

    2013-01-01

    During inflammation, leukocytes play a key role in maintaining tissue homeostasis through elimination of pathogens and removal of damaged tissue. Leukocytes migrate to the site of inflammation by crawling over and through the blood vessel wall, into the tissue. Leukocyte adhesion deficiencies (ie,

  4. Neutrophils, dendritic cells and Toxoplasma.

    Science.gov (United States)

    Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

    2004-03-09

    Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

  5. [The structure of the leukocyte DNA in leukemia patients during chemotherapy].

    Science.gov (United States)

    Tarakanov, M P; Moskaleva, E Iu; Bezobrazova, L V; Semenova, O I; Korneva, E N; Telegin, L Iu

    1993-01-01

    The authors studied the degree of DNA damage in in vitro cultured human peripheral lymphocytes (PL) and Jurcat's human T-cell lymphoma cells exposed to a stabilized 4 OH-cyclophosphan-mamophosphatide (MA) derivative, as well as in the leukocytes from patients with leukemia who were treated with cyclophosphan. There was an increase in alkaline DNA denaturation rate of LP lysates and T-cell lymphoma cells, which was in proportion to MA concentrations, and a higher sensitivity of LP to the genotoxic effect of MA given in doses of 5-10 micrograms/ml than that of Jurcat's cells, as well as high peripheral lymphocyte and neutrophil DNA damages in patients with leukemia during chemotherapy. The authors consider that the accumulation of single-strand breaks and alkaline-labile sites, which was recorded from the increase in alkaline DNA denaturation rate of cell lysates, is a highly sensitive test for detecting DNA damages in resting and slowly proliferating cells and can be useful in revealing and evaluating the severity of human genotoxic effects.

  6. Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of theileria-induced leukocyte transformation

    KAUST Repository

    Hayashida, Kyoko; Hara, Yuichiro; Abe, Takashi; Yamasaki, Chisato; Toyoda, Atsushi; Kosuge, Takehide; Suzuki, Yutaka; Sato, Yoshiharu; Kawashima, Shuichi; Katayama, Toshiaki; Wakaguri, Hiroyuki; Inoue, Noboru; Homma, Keiichi; Tada-Umezaki, Masahito; Yagi, Yukio; Fujii, Yasuyuki; Habara, Takuya; Kanehisa, Minoru; Watanabe, Hidemi; Ito, Kimihito; Gojobori, Takashi; Sugawara, Hideaki; Imanishi, Tadashi; Weir, William; Gardner, Malcolm; Pain, Arnab; Shiels, Brian; Hattori, Masahira; Nene, Vishvanath; Sugimoto, Chihiro

    2012-01-01

    . annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within

  7. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

    Science.gov (United States)

    Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

    2014-03-01

    Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

  8. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

    KAUST Repository

    Zhu, Jiang; Zhang, Huoming; Guo, Tiannan; Li, Wenying; Li, Huiyu; Zhu, Yi; Huang, Shiang

    2014-01-01

    Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

    KAUST Repository

    Zhu, Jiang

    2014-06-11

    Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  12. Clinical symptoms and neutropenia: the balance of neutrophil development, functional activity, and cell death

    NARCIS (Netherlands)

    Kuijpers, Taco W.

    2002-01-01

    Neutrophilic granulocytes form the major type of leukocytes with counts ranging from about 1500-5000 cells/ micro l of blood under normal conditions. Neutrophils protect our body against bacterial and fungal infections. For this purpose, these cells are equipped with a machinery to sense the site of

  13. Optimisation of the CT h4S bioassay for detection of human interleukin-4 secreted by mononuclear cells stimulated by phytohaemaglutinin or by human leukocyte antigen mismatched mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Petersen, Søren Lykke; Russell, Charlotte Astrid; Bendtzen, Klaus

    2002-01-01

    S bioassay detects 5 pg/ml of human recombinant IL-4 with no detection of IL-2 in concentrations below 500 pg/ml. We have found 72 h of culture optimal for detection of IL-2 and IL-4 produced by human mononuclear cells (MNC) in response to stimulation with phytohaemaglutinin and for detection of IL......-2 in human leukocyte antigen (HLA)-mismatched mixed leukocyte culture (MLC). An interindividual variation in cytokine accumulation was demonstrated for IL-4 but not for IL-2. With the use of 5x10(4) responder cells/well no IL-4 could be detected in HLA-mismatched MLC between days 1 and 16. The lack...

  14. Soluble CD40 ligand stimulates CD40-dependent activation of the β2 integrin Mac-1 and protein kinase C zeda (PKCζ in neutrophils: implications for neutrophil-platelet interactions and neutrophil oxidative burst.

    Directory of Open Access Journals (Sweden)

    Rong Jin

    Full Text Available Recent work has revealed an essential involvement of soluble CD40L (sCD40L in inflammation and vascular disease. Activated platelets are the major source of sCD40L, which has been implicated in platelet and leukocyte activation, although its exact functional impact on leukocyte-platelet interactions and the underlying mechanisms remain undefined. We aimed to determine the impact and the mechanisms of sCD40L on neutrophils. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte recruitment to the sites of injury. Our data show that CD40L contributes to neutrophil firm adhesion to and transmigration across activated surface-adherent platelets, possibly through two potential mechanisms. One involves the direct interaction of ligand-receptor (CD40L-CD40, i.e., platelet surface CD40L interaction with neutrophil CD40; another involves an indirect mechanism, i.e. soluble CD40L stimulates activation of the leukocyte-specific β2 integrin Mac-1 in neutrophils and thereby further promotes neutrophil adhesion and migration. Activation of the integrin Mac-1 is known to be critical for mediating neutrophil adhesion and migration. sCD40L activated Mac-1 in neutrophils and enhanced neutrophil-platelet interactions in wild-type neutrophils, but failed to elicit such responses in CD40-deficient neutrophils. Furthermore, our data show that the protein kinase C zeta (PKCζ is critically required for sCD40L-induced Mac-1 activation and neutrophil adhesive function. sCD40L strongly stimulated the focal clustering of Mac-1 (CD11b and the colocalization of Mac-1 with PKCζ in wild-type neutrophils, but had minimal effect in CD40-deficient neutrophils. Blocking PKCζ completely inhibited sCD40L-induced neutrophil firm adhesion. Moreover, sCD40L strongly stimulates neutrophil oxidative burst via CD40-dependent activation of PI3K/NF-KB, but independent of Mac-1 and PKCζ. These findings may contribute to a better

  15. Japanese Society for Laboratory Hematology flow cytometric reference method of determining the differential leukocyte count: external quality assurance using fresh blood samples.

    Science.gov (United States)

    Kawai, Y; Nagai, Y; Ogawa, E; Kondo, H

    2017-04-01

    To provide target values for the manufacturers' survey of the Japanese Society for Laboratory Hematology (JSLH), accurate standard data from healthy volunteers were needed for the five-part differential leukocyte count. To obtain such data, JSLH required an antibody panel that achieved high specificity (particularly for mononuclear cells) using simple gating procedures. We developed a flow cytometric method for determining the differential leukocyte count (JSLH-Diff) and validated it by comparison with the flow cytometric differential leukocyte count of the International Council for Standardization in Haematology (ICSH-Diff) and the manual differential count obtained by microscopy (Manual-Diff). First, the reference laboratory performed an imprecision study of JSLH-Diff and ICSH-Diff, as well as performing comparison among JSLH-Diff, Manual-Diff, and ICSH-Diff. Then two reference laboratories and seven participating laboratories performed imprecision and accuracy studies of JSLH-Diff, Manual-Diff, and ICSH-Diff. Simultaneously, six manufacturers' laboratories provided their own representative values by using automated hematology analyzers. The precision of both JSLH-Diff and ICSH-Diff methods was adequate. Comparison by the reference laboratory showed that all correlation coefficients, slopes and intercepts obtained by the JSLH-Diff, ICSH-Diff, and Manual-Diff methods conformed to the criteria. When the imprecision and accuracy of JSLH-Diff were assessed at seven laboratories, the CV% for lymphocytes, neutrophils, monocytes, eosinophils, and basophils was 0.5~0.9%, 0.3~0.7%, 1.7~2.6%, 3.0~7.9%, and 3.8~10.4%, respectively. More than 99% of CD45 positive leukocytes were identified as normal leukocytes by JSLH-Diff. When JSLH-Diff method were validated by comparison with Manual-Diff and ICSH-Diff, JSLH-Diff showed good performance as a reference method. © 2016 John Wiley & Sons Ltd.

  16. Neutrophil Influx and Chemokine Production during the Early Phases of the Antitumor Response to the Vascular Disrupting Agent DMXAA (ASA404

    Directory of Open Access Journals (Sweden)

    Liang-Chuan S. Wang

    2009-08-01

    Full Text Available 5,6-Dimethylxanthenone-4-acetic acid (DMXAA acts through tumor vascular disruption and cytokine production and is the first of its class to enter phase 3 trials. We characterized leukocytes and cytokines in murine Colon 38 tumors before and after DMXAA treatment. Tumor mass declined 50% 24 hours after DMXAA administration, but the leukocyte count per gram of tumor increased threefold owing to a large influx of Ly6G+CD11b+F4/80−. cells with the morphology of neutrophils. However, B and T lymphocytes, natural killer cells, and macrophages in the tumor all decreased in numbers. Seven chemokines were substantially induced in the tumor, spleen, and serum 4 hours after DMXAA administration. Using cultured spleen cell subpopulations, CD11b+ cells (largely monocytes and macrophages were shown to be the primary producers of tumor necrosis factor á, interleukin 6 (IL-6, and macrophage inflammatory 1α (MIP-1α. CD49b+ natural killer cells produced IP-10, whereas CD45R+ B lymphocytes produced regulated upon activation normal T cell express sequence. T lymphocytes were not major producers of cytokines in the response to DMXAA. Murine peripheral blood leukocytes (PBLs produced a similar panel of cytokines in culture to that detected in mouse serum after DMXAA treatment. Cytokines in human PBL cultures were subsequently measured with the aim of identifying potential serum markers of the human response to DMXAA. IP-10 (P < .001, monocyte chemoattractant protein 1 (P < .001, and sCD40L (P < .01 were decreased, whereas IL-8 (P < .001 and MIP-1α (P = .03 were increased in DMXAA-treated compared with untreated PBL cultures from a group of 12 donors.

  17. Indirect evidence for a role of a subpopulation of activated neutrophils in the remodelling process after percutaneous coronary intervention

    NARCIS (Netherlands)

    Costa, MA; de Wit, LEA; de Valk, V.; Serrano, P; Wardeh, AJ; Serruys, PW; Sluiter, W

    Aim Leukocytes have been implicated in restenosis following percutaneous transluminal coronary angioplasty. We investigated the link between the activated status of circulating neutrophils and restenosis after angioplasty. Methods and Results The population of 108 patients with single, de novo

  18. Comparison of metabolic, hematological, and peripheral blood leukocyte cytokine profiles of dairy cows and heifers during the periparturient period.

    Science.gov (United States)

    Jonsson, N N; Fortes, M R S; Piper, E K; Vankan, D M; de Cisneros, J Prada J; Wittek, T

    2013-04-01

    The periparturient period presents major physiological challenges for the dairy cow. It is a period that is affected by metabolic stressors, major changes in endocrine status, and altered immune function, which together result in an increased risk of disease. Immunological, hematological, and metabolic profiles from the periparturient period of heifers (primipara) were compared with those of cows (pluripara) to test the hypothesis that at the time of calving they have qualitatively different peripheral blood profiles. Blood samples were collected from 22 Holstein-Friesian animals on 3 occasions: approximately 2 wk before calving, within 24h after calving, and approximately 2 wk after calving. Quantitative PCR was used to measure the expression of a selected set of cytokines and receptors by peripheral blood leukocytes. Additional analyses included hemoglobin concentration, red cell, platelet and white cell counts (total and differentiated), and clinical diagnostic biochemical profiles. Total leukocyte counts, neutrophils, and lymphocytes were higher in heifers than cows before calving and within 24h after calving. Alkaline phosphatase was consistently higher in heifers than cows and several significant differences were observed between the 2 groups with regards to cytokine and cytokine-receptor mRNA expression. The results warrant further investigation from the perspective of identifying risk factors for metabolic and parturient disease in dairy cattle. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Neutrophils at work

    DEFF Research Database (Denmark)

    Nauseef, William M; Borregaard, Niels

    2014-01-01

    In this Review we discuss data demonstrating recently recognized aspects of neutrophil homeostasis in the steady state, granulopoiesis in 'emergency' conditions and interactions of neutrophils with the adaptive immune system. We explore in vivo observations of the recruitment of neutrophils from ...

  20. Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles.

    Science.gov (United States)

    Ramishetti, Srinivas; Landesman-Milo, Dalit; Peer, Dan

    2016-11-01

    Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens and defend the body through a complex network. They are also involved in the pathogeneses of inflammation, viral infection, autoimmunity and cancers. Modulating gene expression in leukocytes using siRNAs holds great promise to treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce with siRNAs and are spread throughout the body often located deep in tissues, therefore developing an efficient systemic delivery strategy is still a challenge. Here, we discuss recent advances in siRNA delivery to leukocyte subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus mainly on lipid-based nanoparticles (LNPs) comprised of new generation of ionizable lipids and their ability to deliver siRNA to primary or malignant leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to subsets of leukocytes and we detail a novel microfluidic mixing technology that could aid in changing the landscape of process development of LNPs from a lab tool to a potential novel therapeutic modality.

  1. Chronic neutrophilic leukemia.

    Science.gov (United States)

    Bredeweg, Arthur; Burch, Micah; Krause, John R

    2018-01-01

    Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

  2. Neutrophils in critical illness.

    Science.gov (United States)

    McDonald, Braedon

    2018-03-01

    During critical illness, dramatic alterations in neutrophil biology are observed including abnormalities of granulopoeisis and lifespan, cell trafficking and antimicrobial effector functions. As a result, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. In this article, the role of neutrophils in the pathogenesis of critical illness (sepsis, trauma, burns and others) will be explored, including pathological changes to neutrophil function during critical illness and the utility of monitoring aspects of the neutrophil phenotype as biomarkers for diagnosis and prognostication. Lastly, we review findings from clinical trials of therapies that target the harmful effects of neutrophils, providing a bench-to-bedside perspective on neutrophils in critical illness.

  3. Obesity is associated with more activated neutrophils in African American male youth.

    Science.gov (United States)

    Xu, X; Su, S; Wang, X; Barnes, V; De Miguel, C; Ownby, D; Pollock, J; Snieder, H; Chen, W; Wang, X

    2015-01-01

    There is emerging evidence suggesting the role of peripheral blood leukocytes in the pathogenesis of obesity and related diseases. However, few studies have taken a genome-wide approach to investigating gene expression profiles in peripheral leukocytes between obese and lean individuals with the consideration of obesity-related shifts in leukocyte types. We conducted this study in 95 African Americans (AAs) of both genders (age 14-20 years, 46 lean and 49 obese). Complete blood count with differential test (CBC) was performed in whole blood. Genome-wide gene expression analysis was obtained using the Illumina HumanHT-12 V4 Beadchip with RNA extracted from peripheral leukocytes. Out of the 95 participants, 64 had neutrophils stored. The validation study was based on real-time PCR with RNA extracted from purified neutrophils. CBC test suggested that, in males, obesity was associated with increased neutrophil percentage (P=0.03). Genome-wide gene expression analysis showed that, in males, the majority of the most differentially expressed genes were related to neutrophil activation. Validation of the gene expression levels of ELANE (neutrophil elastase) and MPO (myeloperoxidase) in purified neutrophils demonstrated that the expression of these two genes--important biomarkers of neutrophils activation--were significantly elevated in obese males (P=0.01 and P=0.02, respectively). The identification of increased neutrophil percentage and activation in obese AA males suggests that neutrophils have an essential role in the pathogenesis of obesity-related disease. Further functional and mechanistic studies on neutrophils may contribute to the development of novel intervention strategies reducing the burden associated with obesity-related health problems.

  4. Neutrophilic dermatoses in a patient with collagenous colitis

    Directory of Open Access Journals (Sweden)

    Didac Barco

    2010-01-01

    Full Text Available We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate and Sweet’s syndrome was diagnosed. Both the neutrophilic panniculitis and the Sweet’s syndrome were accompanied by fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with corticoid therapy. The two types of neutrophilic dermatoses that appeared in periods of colitis activity suggest that intestinal and cutaneous manifestations may be related.

  5. Inhibition of the mixed leukocyte reaction by alloantisera in man

    International Nuclear Information System (INIS)

    Jonker, M.; Leeuwen, A. van; Rood, J.J. van

    1977-01-01

    The incidence of MLC(mixed leukocyte culture)-inhibiting antibodies was determined in 42 pregnancy sera. MLC's were carried out between the cells from the serum donor and her husband in the presence of nonimmune AB serum and the test serum. Fifty per cent of the sera reduced the MLC response to less than 40% of the control values. Only four sera had lymphocytotoxic activity. The inhibition was strong against the specific immunizor, less strong against random unrelated cells and weak against cells which were SD(serologically defined)-identical with the serum donor. Absorptions with lymphocytes and platelets were carried out. Lymphocytes removed activity in three of the four sera tested. Platelets removed activity from one serum. It was concluded that both anti-LD(lymphocyte defined) and anti-SD antibodies were able to inhibit the MLR (mixed leukocyte reaction) at the stimulator cell level. (author)

  6. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

    2015-01-01

    Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

  7. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

    2015-06-16

    Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Phagocytic and bactericidal activities of leukocytes in whole blood from atomic bomb survivors

    International Nuclear Information System (INIS)

    Sasagawa, S.; Yoshimoto, Y.; Toyota, E.; Neriishi, S.; Yamakido, M.; Matsuo, M.; Hosoda, Y.; Finch, S.C.

    1990-01-01

    This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count

  9. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels

    2013-11-01

    Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

  10. Apoptosis of lymphocytes in SLE: the level, correlation with ...

    African Journals Online (AJOL)

    Lymphocytes were isolated from venous blood by method of gradient centrifugation of all the blood through a Ficoll-pak solution. The quantity apoptotic cells was determined in leukocytes by flow cytometry Epics XL-2 (“Beckman Coulter”, USA). Analysis of lymphocyte subpopulations was carried by using two fluorescent ...

  11. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

    Science.gov (United States)

    Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

    2017-01-01

    Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophilsneutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

  12. Peripheral blood film review. The demise of the eyecount leukocyte differential.

    Science.gov (United States)

    Pierre, Robert V

    2002-03-01

    initiate blood film review based on findings of the CBC and automated differential is a more sensitive and accurate method of detecting patients with blood film abnormalities than routine blood film review of all specimens by technologists. Clinicians need to recognize that daily differential results or differentials at intervals of less than a week are not medically necessary in most patients. The laboratory, however, must provide opportunities for the clinician to request differentials at any time for specific medical reasons. The laboratory must establish the validity of screening criteria for detection of distribution and morphologic abnormalities of leukocytes by clinical correlation studies or adopt criteria established by laboratories with the same instrumentation and which have conducted clinical evaluations. A final observation on the eyecount differential is that it was the only way to identify cell types and their relative proportion for nearly 100 years. Cells were identified by their shape, intracellular structures, and staining characteristics. Many studies were able eventually to correlate some aspect of each cell type's function with their morphologic appearance. It has also been learned that the bone marrow is the source of production of most circulating cells and a great deal of the controls of cell production and release into the peripheral blood have been learned. But leukocytes have many functions, almost none of which are performed in the peripheral blood. The peripheral blood is mainly a conduit from the bone marrow to the tissues where the leukocytes perform their function in the case of the neutrophils and monocytes. It is mainly a recirculation and redistribution system for lymphocytes that usually receive their instructions from antigen processing cells in the tissues and allow these modified cells to home to sites where their functions occur. Cellular morphology and staining characteristics tell little about the maturation stage and functional

  13. A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8.

    Science.gov (United States)

    Kamoshida, Go; Tansho-Nagakawa, Shigeru; Kikuchi-Ueda, Takane; Nakano, Ryuichi; Hikosaka, Kenji; Nishida, Satoshi; Ubagai, Tsuneyuki; Higashi, Shouichi; Ono, Yasuo

    2016-12-01

    Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. © Society for Leukocyte Biology.

  14. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  15. Mitochondria in neutrophil apoptosis

    NARCIS (Netherlands)

    van Raam, B. J.; Verhoeven, A. J.; Kuijpers, T. W.

    2006-01-01

    Central in the regulation of the short life span of neutrophils are their mitochondria. These organelles hardly contribute to the energy status of neutrophils but play a vital role in the apoptotic process. Not only do the mitochondria contain cytotoxic proteins that are released during apoptosis

  16. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

    Science.gov (United States)

    Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

    2013-01-01

    The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

  17. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation.

    Science.gov (United States)

    Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

    2016-01-01

    Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  18. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation

    Directory of Open Access Journals (Sweden)

    Omar Rafael Alemán

    2016-01-01

    Full Text Available Neutrophils (PMN are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  19. Effects of indomethacin on ovarian leukocytes during the periovulatory period in the rat

    Directory of Open Access Journals (Sweden)

    Tarradas Esteban

    2003-02-01

    Full Text Available Abstract We have investigated the effects of indomethacin (IM, a non-steroidal anti-inflammatory drug, and the role of prostaglandins on the accumulation of leukocytes in the rat ovary during the periovulatory period. Adult cycling rats were injected sc with 1 mg of IM in olive oil or vehicle on the morning of proestrus. Some animals were killed at 16:00 h in proestrus. On the evening (19:00 h of proestrus, IM-treated rats were injected with 500 micrograms of prostaglandin E1 in saline or vehicle. Animals were killed at 01:30 and 09:00 h in estrus. There was an influx of macrophages, neutrophils, and eosinophils into the theca layers of preovulatory follicles, and of neutrophils and eosinophils into the ovarian medulla from 16:00 h in proestrus to 01:30 h in estrus. All these changes, except the accumulation of neutrophils in the theca layers of preovulatory follicles, were blocked by IM treatment. At 09:00 h in estrus, large clusters of neutrophils were observed in IM-treated rats, around abnormally ruptured follicles. The accumulation of leukocytes was not restored by prostaglandin supplementation, despite the inhibition of abnormal follicle rupture and restoration of ovulation in these animals. These results suggest that different mechanisms are involved in leukocyte accumulation in the ovary during the periovulatory period, and that the inhibitory effects of IM on the influx of leukocytes are not dependent on prostaglandin synthesis inhibition.

  20. Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes

    DEFF Research Database (Denmark)

    Alhede, Morten; Bjarnsholt, T.; Jensen, P.O.

    2009-01-01

    Polymorphonuclear neutrophilic leukocytes (PMNs) play a central role in innate immunity, where they dominate the response to infections, in particular in the cystic fibrosis lung. PMNs are phagocytic cells that produce a wide range of antimicrobial agents aimed at killing invading bacteria. Howev...

  1. Pathophysiology of neutrophil-mediated extracellular redox reactions.

    Science.gov (United States)

    Jaganjac, Morana; Cipak, Ana; Schaur, Rudolf Joerg; Zarkovic, Neven

    2016-01-01

    Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

  2. Granule protein processing and regulated secretion in neutrophils

    Directory of Open Access Journals (Sweden)

    Avinash eSheshechalam

    2014-09-01

    Full Text Available Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most abundant circulating leukocytes and are vital for rapid immune responses, being recruited to sites of injury or infection within minutes, where they can act as specialized phagocytic cells. However, another prominent function of neutrophils is the release of pro-inflammatory compounds, including cytokines, chemokines and digestive enzymes, which are stored in intracellular compartments and released through regulated exocytosis. Hence, an important feature that contributes to rapid immune responses is capacity of neutrophils to synthesize and store pre-formed pro-inflammatory mediators in specialized intracellular vesicles and thus no new synthesis is required. This review will focus on advancement in three topics relevant to neutrophil secretion. First we will examine what is known about basal level pro-inflammatory mediator synthesis, trafficking and storage in secretory compartments. Second, we will review recent advancements in the mechanisms that control vesicle mobilization and the release of pre-formed mediators. Third, we will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection.

  3. Differential Susceptibility of Bighorn Sheep (Ovis canadensis) and Domestic Sheep (Ovis aries) Neutrophils to Mannheimia haemolytica Leukotoxin is not due to Differential Expression of Cell Surface CD18.

    Science.gov (United States)

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Liu, Weiguo; Casas, Eduardo; Srikumaran, Subramaniam

    2017-07-01

    Bighornsheep ( Ovis canadensis ) are more susceptible to pneumonia caused by Mannheimia haemolytica than are domestic sheep ( Ovis aries ). Leukotoxin produced by M. haemolytica is the principal virulence factor involved in pneumonia pathogenesis. Although leukotoxin is cytolytic to all subsets of ruminant leukocytes, neutrophils are the most susceptible subset. Bighorn sheep neutrophils are four- to eightfold more susceptible to leukotoxin-induced cytolysis than are domestic sheep neutrophils. We hypothesized that the higher susceptibility of bighorn sheep neutrophils, in comparison to domestic sheep neutrophils, is due to higher expression of CD18, the receptor for leukotoxin on leukocytes. Our objective was to quantify CD18 expression on neutrophils of bighorn sheep and domestic sheep. Cell-surface CD18 expression on bighorn sheep and domestic sheep neutrophils was measured as antibody binding capacity of cells by flow cytometric analysis with two fluorochrome-conjugated anti-CD18 monoclonal antibodies (BAQ30A and HUH82A) and microspheres. Contrary to our expectations, CD18 expression was higher (Psheep neutrophils in comparison to bighorn sheep neutrophils. These findings suggest that the higher in vitro susceptibility to leukotoxin of bighorn sheep neutrophils compared to domestic sheep neutrophils is not due to higher expression of the leukotoxin receptor CD18 on bighorn sheep neutrophils.

  4. Correlation between Leukocyte Numbers and Body Size of Rainbow Trout

    DEFF Research Database (Denmark)

    Mohammad, Rezkar Jaafar; Otani, Maki; Kania, Per Walter

    2016-01-01

    wild and cultured fish and we show that the size of the leukocyte population increases exponentially with body size of rainbow trout. Four groups (5 fish/group) of naive rainbow trout (Oncorhynchus mykiss) with a mean body weight of 2 - 4 g (group I), 4 - 6 g (group II), 25 - 30 g (group III), and 650...... towards an antigen to be initiated even in fry. The number of leukocytes in individual fish at different developmental stages is likely to influence the capacity of the fish to respond simultaneously to several antigens (pathogens and vaccine components). This parameter may therefore be crucial for both...... - 780 g (group IV) were investigated. The number of lymphocytes was generally higher in head kidney compared to blood and spleen but they dominated in all samples (blood, head kidney and spleen) and their numbers increased exponentially with fish size. Percentages of lymphocytes in relation...

  5. Selective suppression of leukocyte recruitment in allergic inflammation

    Directory of Open Access Journals (Sweden)

    CL Weller

    2005-03-01

    Full Text Available Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.

  6. Urokinase-type plasminogen activator receptor plays a role in neutrophil migration during lipopolysaccharide-induced peritoneal inflammation but not during Escherichia coli-induced peritonitis

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Urokinase-type plasminogen activator receptor (uPAR) is expressed on many different cells, including leukocytes. uPAR has been implicated to play a role in neutrophil migration to sites of inflammation. METHODS: To determine the role that uPAR plays in neutrophil recruitment in response

  7. Analysis of leukocyte binding to depletion filters: role of passive binding, interaction with platelets, and plasma components.

    Science.gov (United States)

    Henschler, R; Rüster, B; Steimle, A; Hansmann, H L; Walker, W; Montag, T; Seifried, E

    2005-08-01

    Since limited knowledge exists on the mechanisms which regulate cell binding to leukocyte removal filter surfaces, we investigated the binding patterns of leukocytes to individual layers of leukocyte depletion filters. After passage of 1 unit of whole blood, blotting of isolated filter layers on glass slides or elution of cells from filter layers revealed that most leukocytes were located within the first 10 of a total of 28 filter layers, peaking at layers 6 to 8, with granulocytes binding on average to earlier filter layers than lymphocytes. Leukocytes preincubated with inhibitors of actin activation showed unchanged distribution between filter layers, suggesting that cytoskeletal activation does not significantly contribute to their binding. When leukocytes were directly incubated with single filter layers, binding of up to 30% of input cells was recorded in the absence of Ca(2+). Immunohistological analyses showed colocalization of platelets and leukocytes, with co-clustering of platelets and leukocytes. Monocytes and to some degree lymphocytes but not granulocytes competed with platelets for filter binding. Precoating of filter layers with individual plasma components showed that hyaluronic acid, plasma type fibronectin, and fibrinogen all increased the binding of leukocytes compared with albumin coating. In conclusion, leukocytes can bind passively to filters in a process which does not require Ca(2+), which is independent of cytoskeletal activation and which may depend on individual plasma components. These results are of importance when new selective cell enrichment or depletion strategies through specific filters are envisaged.

  8. Oxidative burst of circulating neutrophils following traumatic brain injury in human.

    Directory of Open Access Journals (Sweden)

    Yiliu Liao

    Full Text Available Besides secondary injury at the lesional site, Traumatic brain injury (TBI can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91(phox in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected

  9. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

    Science.gov (United States)

    Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

    2017-09-01

    Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

  10. A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration

    OpenAIRE

    Lee, Catherine A.; Silva, Milton; Siber, Andrew M.; Kelly, Aaron J.; Galyov, Edouard; McCormick, Beth A.

    2000-01-01

    In response to Salmonella typhimurium, the intestinal epithelium generates an intense inflammatory response consisting largely of polymorphonuclear leukocytes (neutrophils, PMN) migrating toward and ultimately across the epithelial monolayer into the intestinal lumen. It has been shown that bacterial-epithelial cell interactions elicit the production of inflammatory regulators that promote transepithelial PMN migration. Although S. typhimurium can enter intestinal ...

  11. ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia

    NARCIS (Netherlands)

    Woodfin, Abigail; Beyrau, Martina; Voisin, Mathieu-Benoit; Ma, Bin; Whiteford, James R.; Hordijk, Peter L.; Hogg, Nancy; Nourshargh, Sussan

    2016-01-01

    Intracellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed on the cell surface of numerous cell types such as endothelial and epithelial cells, vascular smooth muscle cells, and certain leukocyte subsets. With respect to the latter, ICAM-1 has been detected on neutrophils

  12. Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney Immunopathology and Mortality in Invasive Candidiasis

    Science.gov (United States)

    Lionakis, Michail S.; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I.; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M.

    2012-01-01

    Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1lo to Ccr1high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1+/+ and Ccr1−/− donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ. PMID:22916017

  13. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Directory of Open Access Journals (Sweden)

    Michail S Lionakis

    Full Text Available Invasive candidiasis is the 4(th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo to Ccr1(high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+ and Ccr1(-/- donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

  14. In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model.

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    Koji Tanaka

    Full Text Available Neutrophil extracellular traps (NETs represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

  15. Achyrocline satureioides (Lam. D.C. Hydroalcoholic Extract Inhibits Neutrophil Functions Related to Innate Host Defense

    Directory of Open Access Journals (Sweden)

    Eric Diego Barioni

    2013-01-01

    Full Text Available Achyrocline satureioides (Lam. D.C. is a herb native to South America, and its inflorescences are popularly employed to treat inflammatory diseases. Here, the effects of the in vivo actions of the hydroalcoholic extract obtained from inflorescences of A. satureioides on neutrophil trafficking into inflamed tissue were investigated. Male Wistar rats were orally treated with A. satureioides extract, and inflammation was induced one hour later by lipopolysaccharide injection into the subcutaneous tissue. The number of leukocytes and the amount of chemotactic mediators were quantified in the inflammatory exudate, and adhesion molecule and toll-like receptor 4 (TLR-4 expressions and phorbol-myristate-acetate- (PMA- stimulated oxidative burst were quantified in circulating neutrophils. Leukocyte-endothelial interactions were quantified in the mesentery tissue. Enzymes and tissue morphology of the liver and kidney were evaluated. Treatment with A. satureioides extract reduced neutrophil influx and secretion of leukotriene B4 and CINC-1 in the exudates, the number of rolling and adhered leukocytes in the mesentery postcapillary venules, neutrophil L-selectin, β2-integrin and TLR-4 expression, and oxidative burst, but did not cause an alteration in the morphology and activities of liver and kidney. Together, the data show that A. satureioides extract inhibits neutrophil functions related to the innate response and does not cause systemic toxicity.

  16. Studies on N5-methyltetrahydrofolate-homocystein methyltransferase in normal and leukemia leukocytes.

    Science.gov (United States)

    Peytremann, R; Thorndike, J; Beck, W S

    1975-11-01

    A cobalamin-dependent N5-methyltetra-hydrofolate-homocysteine methyltransferase (methyl-transferase) was demonstrated in unfractioned extracts of human normal and leukemia leukocytes. Activity was substantially reduced in the absence of an added cobalamin derivative. Presumably, this residual activity reflects the endogeneous level of holoenzyme. Enzyme activity was notably higher in lymphoid cells than in myeloid cells. Thus, mean specific activities (+/-SD) were: chronic lymphocytic leukemia lymphocytes, 2.15+/-1.16; normal lymphocytes, 0.91+/-0.59; normal mature granulocytes, 0.15+/-0.10; chronic myelocytic leukemia granulocytes, barely detectable activity. Properties of leukocytes enzymes resembled those of methyltransferases previously studied in bacteria and other animal cells. Granulocytes and chronic myelocytic leukemia cells contain a factor or factors that inhibits Escherichia coli enzyme. The data suggest that the prominence of this cobalamin-dependent enzyme in lymphocytes and other mononuclear cell types may be related to their potential for cell division.

  17. Neutrophil-mediated protection of cultured human vascular endothelial cells from damage by growing Candida albicans hyphae

    International Nuclear Information System (INIS)

    Edwards, J.E. Jr.; Rotrosen, D.; Fontaine, J.W.; Haudenschild, C.C.; Diamond, R.D.

    1987-01-01

    Interactions were studied between human neutrophils and cultured human umbilical vein endothelial cells invaded by Candida albicans. In the absence of neutrophils, progressive Candida germination and hyphal growth extensively damaged endothelial cell monolayers over a period of 4 to 6 hours, as determined both by morphological changes and release of 51 Cr from radiolabeled endothelial cells. Monolayers were completely destroyed and replaced by hyphae after 18 hours of incubation. In contrast, when added 2 hours after the monolayers had been infected with Candida, neutrophils selectively migrated toward and attached to hyphae at points of hyphal penetration into individual endothelial cells (observed by time-lapse video-microscopy). Attached neutrophils spread over hyphal surfaces both within and beneath the endothelial cells; neutrophil recruitment to initial sites of leukocyte-Candida-endothelial cell interactions continued throughout the first 60 minutes of observation. Neutrophil spreading and stasis were observed only along Candida hyphae and at sites of Candida-endothelial cell interactions. These events resulted in 58.0% killing of Candida at 2 hours and subsequent clearance of Candida from endothelial cell monolayers, as determined by microcolony counts and morphological observation. On introduction of additional neutrophils to yield higher ratios of neutrophils to endothelial cells (10 neutrophils:1 endothelial cell), neutrophil migration toward hyphal elements continued. Despite retraction or displacement of occasional endothelial cells by invading Candida and neutrophils, most endothelial cells remained intact, viable, and motile as verified both by morphological observations and measurement of 51 Cr release from radiolabeled monolayers

  18. Predictive value of peripheral blood neutrophil and lymphocyte ratio in patients withhypertension and cardiovascular events in patients with hypertension%高血压患者外周血中性粒细胞与淋巴细胞比例对高血压患者心脑血管事件的预测价值

    Institute of Scientific and Technical Information of China (English)

    任慧玲

    2017-01-01

    目的 探讨高血压患者外周血中性粒细胞与淋巴细胞比值(N/L比值)对高血压患者心脑血管事件的预测价值.方法 选取2013年5月至2014年5月在该院治疗的高血压治疗的660例患者,记录患者纳入研究时外周血N/L比值,所有患者均随访到2016年5月31日,根据患者是否出现心脑血管事件,分为观察组和对照组,对比两组患者白细胞分类结果.采用Logistic回归模型探讨N/L比值对心脑血管事件的预测价值.结果 观察组患者吸烟、糖尿病、高脂血症发病率分别为87.5%、72.5%、77.5%,平均动脉压(MAP)水平为(95±12)mmHg,均明显高于对照组(P<0.05).观察组患者白细胞计数、中性粒细胞比例(N%)、单核细胞计数比例、N/L比值分别为(11.6±2.5)×109/L、(70.8±5.9)%、(8.3±5.5)%、3.7±1.5,均高于对照组患者(P<0.05).N/L上升10%(P=0.04)、MAP升高10 mmHg(P=0.02)、N%上升15%(P=0.03)是心脑血管事件的独立风险因素.结论 N/L比值、MAP是高血压患者心脑血管事件的独立风险因素.%Objective To investigate the predictive value of peripheral blood neutrophil to lymphocyte ratio(N/L ratio) in patients with hypertension.Methods A total of 660 cases hypertension patients were enrolled from May 2013 to May2014.Peripheral blood N/L ratio was recorded.All patients were followed up to May 31,2016.According to the incidence of cardiovascular and cerebrovascular events,all patients divided into observation group(with cardiovascular and cerebrovascular events) and control group(without cardiovascular and cerebrovascular events),and white blood cell classification was compared.Logistic regression model was used to evaluate the value of N/L to predict cardiovascular events.Results The incidence rates of smoking,diabetes and hyperlipidemia in patients of the observation group were 87.5%,72.5% and 77.5%,higher than those of the control group(P<0.05),and the level of mean arterial pressure(MAP) was(95±12) mm

  19. Complement C5a receptor antagonism by protamine and poly-L-Arg on human leukocytes.

    Science.gov (United States)

    Olsen, U B; Selmer, J; Kahl, J U

    1988-01-01

    It is shown that protamine selectively and dose-dependently inhibits complement C5a-induced leukocyte responses such as histamine release from basophils, chemiluminescence and beta-glucuronidase release from neutrophils. Protamine produces parallel rightward displacements of the C5a dose-response curves. The inhibitory capacity of the polypeptide is reversible and disappears following repeated washing of exposed cells. In neutrophils poly-L-Arg similarly and specifically antagonizes C5a-induced chemiluminescence and enzyme release. This polymer alone, however, degranulates basophils and neutrophils, leading to histamine and enzyme release, respectively. It is concluded that on human neutrophils the arginine-rich polycations protamine and poly-L-Arg exhibit a competitive C5a receptor antagonism. In addition, protamine inhibits the C5a receptors on basophils. It is hypothesized that molecular conformations of the arginine-rich polycations might bind reversibly to, and block negatively charged groups at the C5a-receptor sites.

  20. With Friends Like These: The Complex Role of Neutrophils in the Progression of Severe Pneumonia

    Directory of Open Access Journals (Sweden)

    Roger D. Pechous

    2017-05-01

    Full Text Available Pneumonia is a leading cause of death from infection in the United States and across the globe. During pulmonary infection, clear resolution of host inflammatory responses occurs in the absence of appreciable lung damage. Neutrophils are the first wave of leukocytes to arrive in the lung upon infection. After activation, neutrophils traffic from the vasculature via transendothelial migration through the lung interstitium and into the alveolar space. Successful pulmonary immunity requires neutrophil-mediated killing of invading pathogens by phagocytosis and release of a myriad of antimicrobial molecules, followed by resolution of inflammation, neutrophil apoptosis, and clearing of dead or dying neutrophils by macrophages. In addition to their antimicrobial role, it is becoming clear that neutrophils are also important modulators of innate and adaptive immune responses, primarily through the release of cytokines and recruitment of additional waves of neutrophils into the airways. Though typically essential to combating severe pneumonia, neutrophil influx into the airways is a double-edged sword: Overzealous neutrophil activation can cause severe tissue damage as a result of the release of toxic agents including proteases, cationic polypeptides, cytokines, and reactive oxygen species (ROS aimed at killing invading microbes. In extreme cases, the damage caused by neutrophils and other innate immune mediators become the primary source of morbidity and mortality. Here, we review the complex role of neutrophils during severe pneumonia by highlighting specific molecules and processes that contribute to pulmonary immunity, but can also drive progression of severe disease. Depending on the identity of the infectious agent, enhancing or suppressing neutrophil-mediated responses may be key to effectively treating severe and typically lethal pneumonia.

  1. Cryopreservation of Human Mucosal Leukocytes.

    Directory of Open Access Journals (Sweden)

    Sean M Hughes

    Full Text Available Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible.To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension.Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

  2. Selection of reliable reference genes for quantitative real-time PCR in human T cells and neutrophils

    Directory of Open Access Journals (Sweden)

    Ledderose Carola

    2011-10-01

    Full Text Available Abstract Background The choice of reliable reference genes is a prerequisite for valid results when analyzing gene expression with real-time quantitative PCR (qPCR. This method is frequently applied to study gene expression patterns in immune cells, yet a thorough validation of potential reference genes is still lacking for most leukocyte subtypes and most models of their in vitro stimulation. In the current study, we evaluated the expression stability of common reference genes in two widely used cell culture models-anti-CD3/CD28 activated T cells and lipopolysaccharide stimulated neutrophils-as well as in unselected untreated leukocytes. Results The mRNA expression of 17 (T cells, 7 (neutrophils or 8 (unselected leukocytes potential reference genes was quantified by reverse transcription qPCR, and a ranking of the preselected candidate genes according to their expression stability was calculated using the programs NormFinder, geNorm and BestKeeper. IPO8, RPL13A, TBP and SDHA were identified as suitable reference genes in T cells. TBP, ACTB and SDHA were stably expressed in neutrophils. TBP and SDHA were also the most stable genes in untreated total blood leukocytes. The critical impact of reference gene selection on the estimated target gene expression is demonstrated for IL-2 and FIH expression in T cells. Conclusions The study provides a shortlist of suitable reference genes for normalization of gene expression data in unstimulated and stimulated T cells, unstimulated and stimulated neutrophils and in unselected leukocytes.

  3. N-Formyl-Perosamine Surface Homopolysaccharides Hinder the Recognition of Brucella abortus by Mouse Neutrophils.

    Science.gov (United States)

    Mora-Cartín, Ricardo; Chacón-Díaz, Carlos; Gutiérrez-Jiménez, Cristina; Gurdián-Murillo, Stephany; Lomonte, Bruno; Chaves-Olarte, Esteban; Barquero-Calvo, Elías; Moreno, Edgardo

    2016-06-01

    Brucella abortus is an intracellular pathogen of monocytes, macrophages, dendritic cells, and placental trophoblasts. This bacterium causes a chronic disease in bovines and in humans. In these hosts, the bacterium also invades neutrophils; however, it fails to replicate and just resists the killing action of these leukocytes without inducing significant activation or neutrophilia. Moreover, B. abortus causes the premature cell death of human neutrophils. In the murine model, the bacterium is found within macrophages and dendritic cells at early times of infection but seldom in neutrophils. Based on this observation, we explored the interaction of mouse neutrophils with B. abortus In contrast to human, dog, and bovine neutrophils, naive mouse neutrophils fail to recognize smooth B. abortus bacteria at early stages of infection. Murine normal serum components do not opsonize smooth Brucella strains, and neutrophil phagocytosis is achieved only after the appearance of antibodies. Alternatively, mouse normal serum is capable of opsonizing rough Brucella mutants. Despite this, neutrophils still fail to kill Brucella, and the bacterium induces cell death of murine leukocytes. In addition, mouse serum does not opsonize Yersinia enterocolitica O:9, a bacterium displaying the same surface polysaccharide antigen as smooth B. abortus Therefore, the lack of murine serum opsonization and absence of murine neutrophil recognition are specific, and the molecules responsible for the Brucella camouflage are N-formyl-perosamine surface homopolysaccharides. Although the mouse is a valuable model for understanding the immunobiology of brucellosis, direct extrapolation from one animal system to another has to be undertaken with caution. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

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    Hossain Mokarram

    2012-07-01

    Full Text Available Abstract Background Nitric oxide (NO is a multifunctional signaling molecule that regulates important cellular events in inflammation including leukocyte recruitment. Previous studies have shown that pharmacological inhibition of NO synthesis induces leukocyte recruitment in various in vitro and animal models. However, it is not known whether NO modulation has similar effects on leukocyte-endothelial cell interactions within the human microvasculature. The present study explored the effect of systemic L-NAME treatment on leukocyte recruitment in the SCID-hu mouse model. Methods Human skin xenografts were transplanted in SCID mice to study human leukocyte dynamics in human vasculature. Early events of human leukocyte recruitment in human vasculature were studied using intravital microscopy. NO synthesis was pharmacologically inhibited using NG-nitro-L-arginine methyl ester (L-NAME. Immunohistochemical analysis was performed to elucidate E-selectin expression in human xenograft skin. Human neutrophil-endothelial cell interactions were also studied in an in vitro flow chamber assay system. P- and E-selectin expression on cultured human umbilical vein endothelial cells (HUVECs was measured using ELISA. Platelet-activating factor (PAF synthesis was detected using a TLC-based assay. Results L-NAME treatment significantly enhanced the rolling and adhesion of human leukocytes to the human vasculature. Functional blocking of P- and E-selectins significantly inhibited rolling but not adhesion induced by inhibition of NO synthesis. Systemic L-NAME treatment enhanced E-selectin expression in human xenograft skin. L-NAME treatment significantly enhanced P- and E-selectin expression on HUVECs. L-NAME treatment did not significantly modify neutrophil rolling or adhesion to HUVECs indicating that L-NAME−induced subtle P- and E-selectin expression was insufficient to elicit dynamic neutrophil-HUVEC interactions in vitro. Moreover, synthesis of endothelial

  5. Delayed polymorphonuclear leukocyte infiltration is an important component of Thalassophryne maculosa venom pathogenesis.

    Science.gov (United States)

    Pareja-Santos, Alessandra; Oliveira Souza, Valdênia Maria; Bruni, Fernanda M; Sosa-Rosales, Josefina Ines; Lopes-Ferreira, Mônica; Lima, Carla

    2008-07-01

    Thalassophryne maculosa fish envenomation is characterized by severe pain, dizziness, fever, edema and necrosis. Here, the dynamic of cellular influx, activation status of phagocytic cells, and inflammatory modulator production in the acute inflammatory response to T. maculosa venom was studied using an experimental model. Leukocyte counting was performed (2 h to 21 days) after venom injection in BALB/c mice footpads. Our results showed an uncommon leukocyte migration kinetic after venom injection, with early mononuclear cell recruitment followed by elevated and delayed neutrophil influx. The pattern of chemokine expression is consistent with the delay in neutrophil recruitment to the footpad: T. maculosa venom stimulated an early production of IL-1beta, IL-6, and MCP-1, but was unable to induce an effective early TNF-alpha and KC release. Complementary to these observations, we detected a marked increase in soluble KC and TNF-alpha in footpad at 7 days post-venom injection when a prominent influx of neutrophils was also detected. In addition, we demonstrated that bone marrow-derived macrophages and dendritic cells were strongly stimulated by the venom, showing up-regulated ability to capture FITC-dextran. Thus, the reduced levels of KC and TNF-alpha in footpad of mice concomitant with a defective accumulation of neutrophils at earlier times provide an important clue to uncovering the mechanism by which T. maculosa venom regulates neutrophil movement.

  6. Measurement of leukocyte rheology in vascular disease: clinical rationale and methodology. International Society of Clinical Hemorheology.

    Science.gov (United States)

    Wautier, J L; Schmid-Schönbein, G W; Nash, G B

    1999-01-01

    The measurement of leukocyte rheology in vascular disease is a recent development with a wide range of new opportunities. The International Society of Clinical Hemorheology has asked an expert panel to propose guidelines for the investigation of leukocyte rheology in clinical situations. This article first discusses the mechanical, adhesive and related functional properties of leukocytes (especially neutrophils) which influence their circulation, and establishes the rationale for clinically-related measurements of parameters which describe them. It is concluded that quantitation of leukocyte adhesion molecules, and of their endothelial receptors may assist understanding of leukocyte behaviour in vascular disease, along with measurements of flow resistance of leukocytes, free radical production, degranulation and gene expression. For instance, vascular cell adhesion molecule (VCAM-1) is abnormally present on endothelial cells in atherosclerosis, diabetes mellitus and inflammatory conditions. Soluble forms of intercellular adhesion molecule (ICAM-1) or VCAM can be found elevated in the blood of patients with rheumatoid arthritis or infections disease. In the second part of the article, possible technical approaches are presented and possible avenues for leukocyte rheological investigations are discussed.

  7. Bare lymphocyte syndrome: imaging findings in an adult

    International Nuclear Information System (INIS)

    Bernaerts, A.; Vandevenne, J.E.; De Schepper, A.M.; Lambert, J.; De Clerck, L.S.

    2001-01-01

    Bare lymphocyte syndrome (BLS) is a rare primary immune disorder characterized by defective expression of human leukocyte antigen (HLA) on lymphocytes, often resulting in extensive and recurrent multi-organ infections. We describe a previously undiagnosed case of an adult woman who presented with radiological findings of severe bronchiectases, near-total granulomatous destruction of facial bones, and osteomyelitis. Diagnosis of BLS should be considered when evaluating children with unexplained bronchiectases or adults with long history of chronic multi-organ infections. (orig.)

  8. Lymphatic pump treatment mobilizes leukocytes from the gut associated lymphoid tissue into lymph.

    Science.gov (United States)

    Hodge, Lisa M; Bearden, Melissa K; Schander, Artur; Huff, Jamie B; Williams, Arthur; King, Hollis H; Downey, H Fred

    2010-06-01

    Lymphatic pump techniques (LPT) are used clinically by osteopathic practitioners for the treatment of edema and infection; however, the mechanisms by which LPT enhances lymphatic circulation and provides protection during infection are not understood. Rhythmic compressions on the abdomen during LPT compress the abdominal area, including the gut-associated lymphoid tissues (GALT), which may facilitate the release of leukocytes from these tissues into the lymphatic circulation. This study is the first to document LPT-induced mobilization of leukocytes from the GALT into the lymphatic circulation. Catheters were inserted into either the thoracic or mesenteric lymph ducts of dogs. To determine if LPT enhanced the release of leukocytes from the mesenteric lymph nodes (MLN) into lymph, the MLN were fluorescently labeled in situ. Lymph was collected during 4 min pre-LPT, 4 min LPT, and 10 min following cessation of LPT. LPT significantly increased lymph flow and leukocytes in both mesenteric and thoracic duct lymph. LPT had no preferential effect on any specific leukocyte population, since neutrophil, monocyte, CD4+ T cell, CD8+ T cell, IgG+B cell, and IgA+B cell numbers were similarly increased. In addition, LPT significantly increased the mobilization of leukocytes from the MLN into lymph. Lymph flow and leukocyte counts fell following LPT treatment, indicating that the effects of LPT are transient. LPT mobilizes leukocytes from GALT, and these leukocytes are transported by the lymphatic circulation. This enhanced release of leukocytes from GALT may provide scientific rationale for the clinical use of LPT to improve immune function.

  9. Unsupervised explorative data analysis of normal human leukocytes and BCR/ABL positive leukemic cells mid-infrared spectra

    NARCIS (Netherlands)

    Bellisola, G.; Bolomini-Vittori, M.; Cinque, G.; Dumas, P.; Fiorini, Z.; Laudanna, C.; Mirenda, M.; Sandt, C.; Silvestri, G.; Tomasello, L.; Vezzalini, M.; Wehbe, K.; Sorio, C.

    2015-01-01

    We proved the ability of Fourier Transform Infrared microspectroscopy (microFTIR) complemented by Principal Component Analysis (PCA) to detect protein phosphorylation/de-phosphorylation in mammalian cells. We analyzed by microFTIR human polymorphonuclear neutrophil (PMNs) leukocytes, mouse-derived

  10. Effects of ketotifen on human lymphocytes in vitro and in vivo

    NARCIS (Netherlands)

    Petrasch, S.; van Tits, L. J.; Motulsky, H. J.; Brodde, O. E.; Michel, M. C.

    1993-01-01

    The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen-

  11. Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

    International Nuclear Information System (INIS)

    Hau, D.M.

    1984-01-01

    The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats

  12. Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Hau, D.M.

    The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats.

  13. Pattern of CD4 T‑lymphocyte Values in Cancer Patients on Cytotoxic ...

    African Journals Online (AJOL)

    Background: Assessment of patients prior to cytotoxic chemotherapy usually includes absolute neutrophils count. Other cellular markers of susceptibility to infection as well as immunocompetence include the T Helper lymphocyte count. In cancer patients, decrease in these lymphocytes has been observed to be associated ...

  14. Susceptibility of different leukocyte cell types to Vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Sánchez-Puig Juana M

    2004-11-01

    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  15. Imaging neutrophil migration dynamics using micro-optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Chu, Kengyeh K.; Yonker, Lael; Som, Avira; Pazos, Michael; Kusek, Mark E.; Hurley, Bryan P.; Tearney, Guillermo J.

    2016-03-01

    Neutrophils are immune cells that undergo chemotaxis, detecting and migrating towards a chemical signal gradient. Neutrophils actively migrate across epithelial boundaries, interacting with the epithelium to selectively permit passage without compromising the epithelial barrier. In many inflammatory disorders, excessive neutrophil migration can cause damage to the epithelium itself. The signaling pathways and mechanisms that facilitate trans-epithelial migration are not fully characterized. Our laboratory has developed micro-optical coherence tomography (μOCT), which has 2 μm lateral resolution and 1 μm axial resolution. As a high-resolution native contrast modality, μOCT can directly visualize individual neutrophils as they interact with a cell layer cultured on a transwell filter. A chemoattractant can be applied to the apical side of inverted monolayer, and human neutrophils placed in the basolateral compartment, while μOCT captures 3D images of the chemotaxis. μOCT images can also generate quantitative metrics of migration volume to study the dependence of chemotaxis on monolayer cell type, chemoattractant type, and disease state of the neutrophils. For example, a disease known as leukocyte adhesion deficiency (LAD) can be simulated by treating neutrophils with antibodies that interfere with the CD18 receptor, a facilitator of trans-epithelial migration. We conducted a migration study of anti-CD18 treated and control neutrophils using T84 intestinal epithelium as a barrier. After one hour, μOCT time-lapse imaging indicated a strong difference in the fraction of neutrophils that remain attached to the epithelium after migration (0.67 +/- 0.12 attached anti-CD18 neutrophils, 0.23 +/- 0.08 attached control neutrophils, n = 6, p < 0.05), as well as a modest but non-significant decrease in total migration volume for treated neutrophils. We can now integrate μOCT-derived migration metrics with simultaneously acquired measurements of transepithelial electrical

  16. Mild episodes of tourniquet-induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers

    Directory of Open Access Journals (Sweden)

    Bastawrous Salah S

    2007-05-01

    Full Text Available Abstract Background Monocytes and neutrophils are examples of phagocytic leukocytes, with neutrophils being considered as the 'chief' phagocytic leukocyte. Both monocytes and neutrophils have been implicated to play a key role in the development of ischaemia-reperfusion injury, where they are intrinsically involved in leukocyte-endothelial cell interactions. In this pilot study we hypothesised that mild episodes of tourniquet induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers. Methods Ten healthy human volunteers were recruited after informed consent. None had any history of cardiovascular disease with each subject volunteer participating in the study for a 24 hour period. Six venous blood samples were collected from each subject volunteer at baseline, 10 minutes ischaemia, 5, 15, 30, 60 minutes and 24 hours reperfusion, by means of a cannula from the ante-cubital fossa. Monocyte and neutrophil leukocyte sub-populations were isolated by density gradient centrifugation techniques. Leukocyte trapping was investigated by measuring the concentration of leukocytes in venous blood leaving the arm. The cell surface expression of CD62L (L-selectin, CD11b and the intracellular production of hydrogen peroxide (H2O2 were measured via flow cytometry. C-reactive protein (CRP was measured using a clinical chemistry analyser. Plasma concentrations of D-dimer and von Willebrand factor (vWF were measured using enzyme-linked fluorescent assays (ELFA. Results During ischaemia-reperfusion injury, there was a decrease in CD62L and an increase in CD11b cell surface expression for both monocytes and neutrophils, with changes in the measured parameters reaching statistical significance (p =2O2 production by leukocyte sub-populations, which was measured as a marker of leukocyte activation. Intracellular production of H2O2 in monocytes during ischaemia-reperfusion injury reached statistical

  17. Total hip and knee replacement surgery results in changes in leukocyte and endothelial markers

    Directory of Open Access Journals (Sweden)

    Maclean Kirsty M

    2010-01-01

    Full Text Available Abstract Background It is estimated that over 8 million people in the United Kingdom suffer from osteoarthritis. These patients may require orthopaedic surgical intervention to help alleviate their clinical condition. Investigations presented here was to test the hypothesis that total hip replacement (THR and total knee replacement (TKR orthopaedic surgery result in changes to leukocyte and endothelial markers thus increasing inflammatory reactions postoperatively. Methods During this 'pilot study', ten test subjects were all scheduled for THR or TKR elective surgery due to osteoarthritis. Leukocyte concentrations were measured using an automated full blood count analyser. Leukocyte CD11b (Mac-1 and CD62L cell surface expression, intracellular production of H2O2 and elastase were measured as markers of leukocyte function. Von Willebrand factor (vWF and soluble intercellular adhesion molecule-1 (sICAM-1 were measured as markers of endothelial activation. Results The results obtained during this study demonstrate that THR and TKR orthopaedic surgery result in similar changes of leukocyte and endothelial markers, suggestive of increased inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in a leukocytosis, this being demonstrated by an increase in the total leukocyte concentration following surgery. Evidence of leukocyte activation was demonstrated by a decrease in CD62L expression and an increase in CD11b expression by neutrophils and monocytes respectively. An increase in the intracellular H2O2 production by neutrophils and monocytes and in the leukocyte elastase concentrations was also evident of leukocyte activation following orthopaedic surgery. With respect to endothelial activation, increases in vWF and sICAM-1 concentrations were demonstrated following surgery. Conclusion In general it appeared that most of the leukocyte and endothelial markers measured during these studies peaked between days 1

  18. Altered expression of adhesion molecules on peripheral blood leukocytes in feline infectious peritonitis.

    Science.gov (United States)

    Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Desmarets, Lowiese M B; Vermeulen, Ben L; Dewerchin, Hannah L; Nauwynck, Hans J

    2013-10-25

    Feline infectious peritonitis (FIP) is a fatal, coronavirus-induced systemic disease in domestic and wild felids. The pathology associated with FIP (multifocal granulomatous vasculitis) is considered to be elicited by exaggerated activation and subsequent extravasation of leukocytes. As changes in the expression of adhesion molecules on circulating leukocytes precede their margination and emigration, we reasoned that the expression of leukocyte adhesion molecules may be altered in FIP. In present study, the expression of principal adhesion molecules involved in leukocyte transmigration (CD15s, CD11a, CD11b, CD18, CD49d, and CD54) on peripheral blood leukocytes from cats with naturally occurring FIP (n=15) and controls (n=12) was quantified by flow cytometry using a formaldehyde-based rapid leukocyte preparation technique. T- and B-lymphocytes from FIP patients exhibit higher expression of both subunits (CD11a and CD18) composing the β2 integrin lymphocyte function-associated antigen (LFA)-1. In addition, the expression of the α4 subunit (CD49d) of the β1 integrin very late antigen (VLA)-4 was elevated on B-lymphocytes from FIP patients. The expression of CD11b and CD18, that combine to form the β2 integrin macrophage-1 antigen (Mac-1), was elevated on monocytes, whereas the density of CD49d was reduced on this population in FIP. Granulocytes of FIP cats displayed an increased expression of the α chain of Mac-1 (CD11b). These observations suggest that leukocytes from FIP patients show signs of systemic activation causing them to extravasate into surrounding tissues and ultimately contribute to pyogranuloma formation seen in FIP. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

    Science.gov (United States)

    Kampschmidt, R F; Upchurch, H F; Worthington, M L

    1983-07-01

    It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

  20. Diagnostic Role of Neutrophil-Lymphocyte Ratio in Oral Cavity ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... operating characteristics curve analysis suggested cutoff value of ... helpful in identifying the oral cavity lesions at high risk for harboring malignancy. ... After taking approval from local ethics committee, ... used for comparison of gender distributions. ... difference in M/F ratio revealed between groups (P =.

  1. Live Brugia malayi microfilariae inhibit transendothelial migration of neutrophils and monocytes.

    Directory of Open Access Journals (Sweden)

    Jan-Hendrik Schroeder

    Full Text Available Lymphatic filariasis is a major tropical disease caused by the parasite Brugia malayi. Microfilariae (Mf circulate in the peripheral blood for 2-3 hours in synchronisation with maximal feeding of the mosquito vector. When absent from the peripheral blood, Mf sequester in the capillaries of the lungs. Mf are therefore in close contact with vascular endothelial cells (EC and may induce EC immune function and/or wound repair mechanisms such as angiogenesis. In this study, Mf were co-cultured with human umbilical vein EC (HUVEC or human lung microvascular EC (HLMVEC and the transendothelial migration of leukocyte subsets was analysed. In addition, the protein and/or mRNA expression of chemokine, cytokine and angiogenic mediators in endothelial cells in the presence of live microfilariae were measured by a combination of cDNA arrays, protein arrays, ELISA and fluorescence antibody tests.Surprisingly, our findings indicate that Mf presence partially blocked transendothelial migration of monocytes and neutrophils, but not lymphocytes. However, Mf exposure did not result in altered vascular EC expression of key mediators of the tethering stage of extravasation, such as ICAM-1, VCAM-1 and various chemokines. To further analyse the immunological function of vascular EC in the presence of Mf, we measured the mRNA and/or protein expression of a number of pro-inflammatory mediators. We found that expression levels of the mediators tested were predominantly unaltered upon B. malayi Mf exposure. In addition, a comparison of angiogenic mediators induced by intact Mf and Wolbachia-depleted Mf revealed that even intact Mf induce the expression of remarkably few angiogenic mediators in vascular EC. Our study suggests that live microfilariae are remarkably inert in their induction and/or activation of vascular cells in their immediate local environment. Overall, this work presents important insights into the immunological function of the vascular endothelium during

  2. Production of antibodies which recognize opiate receptors on murine leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Carr, D.J.J.; Bost, K.L.; Blalock, J.E.

    1988-01-01

    An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, /sup 3/H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with ..beta..-endorphin, meta-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to ..beta..-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

  3. Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis.

    Science.gov (United States)

    Frasson, Amanda Piccoli; De Carli, Geraldo Attilio; Bonan, Carla Denise; Tasca, Tiana

    2012-03-01

    Trichomonas vaginalis is a parasite from the human urogenital tract that causes trichomonosis, the most prevalent non-viral sexually transmitted disease. The neutrophil infiltration has been considered to be primarily responsible for cytological changes observed at infection site, and the chemoattractants can play an important role in this leukocytic recruitment. Nitric oxide (NO) is one of the most widespread mediator compounds, and it is implicated in modulation of immunological mechanisms. Extracellular nucleotides and nucleosides are signaling molecules involved in several processes, including immune responses and control of leukocyte trafficking. Ectonucleoside triphosphate diphosphohydrolase members, ecto-5'-nucleotidase, and adenosine deaminase (ectoADA) have been characterized in T. vaginalis. Herein, we investigated the effects of purinergic system on NO production by neutrophils stimulated with T. vaginalis. The trophozoites were able to induce a high NO synthesis by neutrophils through iNOS pathway. The extracellular nucleotides ATP, ADP, and ATPγS (a non-hydrolyzable ATP analog) showed no significant change in NO secretion. In contrast, adenosine and its degradation product, inosine, promoted a low production of the compound. The immunosuppressive effect of adenosine upon NO release by neutrophils occurred due to adenosine A(2A) receptor activation. The ecto-5'-nucleotidase activity displayed by T. vaginalis was shown to be important in adenosine generation, indicating the efficiency of purinergic cascade. Our data suggest the influence of purinergic signaling, specifically adenosinergic system, on NO production by neutrophils in T. vaginalis infection, contributing to the immunological aspects of disease.

  4. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

    Science.gov (United States)

    von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A.; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T.; Wagner, Denisa D.; Mackman, Nigel; Engelmann, Bernd

    2012-01-01

    Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features. PMID:22451716

  5. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis.

    Science.gov (United States)

    Bhuiyan, Md Saruar; Ellett, Felix; Murray, Gerald L; Kostoulias, Xenia; Cerqueira, Gustavo M; Schulze, Keith E; Mahamad Maifiah, Mohd Hafidz; Li, Jian; Creek, Darren J; Lieschke, Graham J; Peleg, Anton Y

    2016-08-23

    Innate cellular immune responses are a critical first-line defense against invading bacterial pathogens. Leukocyte migration from the bloodstream to a site of infection is mediated by chemotactic factors that are often host-derived. More recently, there has been a greater appreciation of the importance of bacterial factors driving neutrophil movement during infection. Here, we describe the development of a zebrafish infection model to study Acinetobacter baumannii pathogenesis. By using isogenic A. baumannii mutants lacking expression of virulence effector proteins, we demonstrated that bacterial drivers of disease severity are conserved between zebrafish and mammals. By using transgenic zebrafish with fluorescent phagocytes, we showed that a mutation of an established A. baumannii global virulence regulator led to marked changes in neutrophil behavior involving rapid neutrophil influx to a localized site of infection, followed by prolonged neutrophil dwelling. This neutrophilic response augmented bacterial clearance and was secondary to an impaired A. baumannii phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate. Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These data identify a previously unknown mechanism of bacterial-guided neutrophil chemotaxis in vivo, providing insight into the role of bacterial metabolism in host innate immune evasion. Furthermore, the work provides a potentially new therapeutic paradigm of targeting a bacterial metabolic pathway to augment host innate immune responses and attenuate disease.

  6. Role of oncogene 24p3 neutrophil gelatinase-associated lipocalin (NGAL) in digestive system cancers.

    Science.gov (United States)

    Michalak, Łukasz; Bulska, Magdalena; Kudłacz, Katarzyna; Szcześniak, Piotr

    2016-01-04

    Neutrophil gelatinase-associated lipocalin, known also as 24p3 lipocalin, lipocalin-2 or uterocalin (in mouse), is a small secretory protein binding small molecular weight ligands which takes part in numerous processes including apoptosis induction in leukocytes, iron transport, smell, and prostaglandins and retinol transport [19]. It was discovered in activated neutrophils as a covalent peptide associated with human gelatinase neutrophils [7]. Neutrophil lipocalin is secreted physiologically in the digestive system, respiratory tract, renal tubular cells, liver or immunity system. Systematic (circulated in plasma) neutrophil gelatinase come from multiple sources; it may be synthesized in the liver, secreted from activated neutrophils or macrophages, or derive from atherosclerosis or inflammatory endothelial cells [17]. NGAL is stored secondarily in granulates with lactoferrin, calprotectin or MAC-1, which take part in neutrophils' action and migration [13,19]. NGAL participates in acute and chronic inflammation (production of NGAL is indicated by factors conducive to cancer progression) [13,21]. NGAL levels increase in inflammatory or endothelial damage. NGAL level is measured in blood or urine. It is known as a kidney failure factor [7,20]. NGAL is therefore one of the most promising new generation biomarkers in clinical nephrology [6]. The role of NGAL in digestive system neoplasms has not been explored in detail. However, overexpression of this marker was proved in neoplasms such as esophageal carcinoma, stomach cancer, pancreatic cancer or colon cancer, which may indicate an association between concentration and neoplasm [3].

  7. Effects of ghrelin on the apoptosis of human neutrophils in vitro

    Science.gov (United States)

    Li, Bin; Zeng, Mian; Zheng, Haichong; Huang, Chunrong; He, Wanmei; Lu, Guifang; Li, Xia; Chen, Yanzhu; Xie, Ruijie

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and the diffuse infiltration of neutrophils into the alveolar space. Neutrophils are abundant, short-lived leukocytes that play a key role in immune defense against microbial infections. These cells die via apoptosis following the activation and uptake of microbes, and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter pathogens. Apoptosis is essential for the removal of neutrophils from inflamed tissues and for the timely resolution of neutrophilic inflammation. Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor, produced and secreted mainly from the stomach. Previous studies have reported that ghrelin exerts anti-inflammatory effects in lung injury through the regulation of the apoptosis of different cell types; however, the ability of ghrelin to regulate alveolar neutrophil apoptosis remains largely undefined. We hypothesized that ghrelin may have the ability to modulate neutrophil apoptosis. In this study, to examine this hypothesis, we investigated the effects of ghrelin on freshly isolated neutrophils in vitro. Our findings demonstrated a decrease in the apoptotic ratio (as shown by flow cytometry), as well as in the percentage of cells with decreased mitochondrial membrane potential (ΔΨm) and in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling-positive rate, accompanied by an increased B-cell lymphoma 2/Bax ratio and the downregulation of cleaved caspase-3 in neutrophils following exposure to lipopolysaccharide (100 ng/ml). However, pre-treatment with ghrelin at a physiological level (100 nM) did not have a notable influence on the neutrophils in all the aforementioned tests. Our findings suggest that ghrelin may not possess the ability to modulate the neutrophil lifespan in vitro. PMID:27431014

  8. Quantification of deposition of neutrophilic granulocytes on vascular grafts in dogs with 111In-labeled granulocytes

    International Nuclear Information System (INIS)

    Dewanjee, M.K.; Solis, E.; Mackey, S.T.; Socher, S.; Chowdhury, S.; Wu, F.P.; Kaye, M.P.

    1985-01-01

    A new radioisotopic technique has been developed for quantification of deposition of neutrophilic granulocytes on vascular grafts. Nine healthy mongrel dogs underwent bilateral femoral artery resection and reconstruction with grafts of the femoral vein and Gore-Tex. Pure granulocytes that had been separated from whole blood by centrifugal elutriation were labeled with 111 In-tropolone in plasma. The granulocyte harvesting efficiency was 25 +/- 12%, and the labeling efficiency was 87 +/- 7%. Three hours after injection of labeled granulocytes and 2 hours after reperfusion, the grafts were harvested and cut into several segments for study of areas of anastomoses and midsections. On the basis of the radioactivity in the blood and in anastomotic and graft sections, the area of graft sections, and the neutrophilic granulocyte and differential leukocyte counts, the number of neutrophilic granulocytes adherent to a unit area and the total number of neutrophilic granulocytes on graft sections were calculated. These quantifications of the deposition of neutrophilic granulocytes indicated that the midsections of Gore-Tex grafts retained more neutrophilic granulocytes than did the midsections of vein grafts. Although the anastomotic areas retained more neutrophilic granulocytes than did the midsections of vein grafts, the opposite finding prevailed for the Gore-Tex grafts. A major fraction of neutrophilic granulocytes on Gore-Tex grafts was incorporated into the thrombus. Semiquantitative information obtained by scintigraphy of the deposition of neutrophilic granulocytes on vascular grafts also confirmed this observation

  9. Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis.

    Science.gov (United States)

    van Lent, P L; Licht, R; Dijkman, H; Holthuysen, A E; Berden, J H; van den Berg, W B

    2001-11-01

    Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.

  10. Activation of human leukocytes on tantalum trabecular metal in comparison to commonly used orthopedic metal implant materials.

    Science.gov (United States)

    Schildhauer, T A; Peter, E; Muhr, G; Köller, M

    2009-02-01

    We analyzed leukocyte functions and cytokine response of human leukocytes toward porous tantalum foam biomaterial (Trabecular Metaltrade mark, TM) in comparison to equally sized solid orthopedic metal implant materials (pure titanium, titanium alloy, stainless steel, pure tantalum, and tantalum coated stainless steel). Isolated peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophil leukocytes (PMN) were cocultured with equally sized metallic test discs for 24 h. Supernatants were analyzed for cytokine content by enzyme-linked immunosorbent assay. Compared to the other used test materials there was a significant increase in the release of IL (interleukin)-1ra and IL-8 from PMN, and of IL-1ra, IL-6, and TNF-alpha from PBMC in response to the TM material. The cytokine release correlated with surface roughness of the materials. In contrast, the release of IL-2 was not induced showing that mainly myeloid leukocytes were activated. In addition, supernatants of these leukocyte/material interaction (conditioned media, CM) were subjected to whole blood cell function assays (phagocytosis, chemotaxis, bacterial killing). There was a significant increase in the phagocytotic capacity of leukocytes in the presence of TM-conditioned media. The chemotactic response of leukocytes toward TM-conditioned media was significantly higher compared to CM obtained from other test materials. Furthermore, the bactericidal capacity of whole blood was enhanced in the presence of TM-conditioned media. These results indicate that leukocyte activation at the surface of TM material induces a microenvironment, which may enhance local host defense mechanisms.

  11. Neutrophil extracellular traps - the dark side of neutrophils

    DEFF Research Database (Denmark)

    Sørensen, Ole E.; Borregaard, Niels

    2016-01-01

    Neutrophil extracellular traps (NETs) were discovered as extracellular strands of decondensed DNA in complex with histones and granule proteins, which were expelled from dying neutrophils to ensnare and kill microbes. NETs are formed during infection in vivo by mechanisms different from those ori...

  12. Leukocyte apoptosis as a predictor of radiosensitivity in Fanconi anemia

    International Nuclear Information System (INIS)

    Petrovic, Sandra; Leskovac, Andreja; Joksic, Ivana; Filipovic, Jelena; Joksic, Gordana; Vujic, Dragana; Guc-Scekic, Marija

    2013-01-01

    Fanconi anemia (FA) is a rare cancer-prone genetic disease characterized by impaired oxygen metabolism and defects in DNA damage repair. Response of FA cells to ionizing radiation has been an issue intensively debated in the literature. To study in vitro radiosensitivity in patients suffering from FA and their parents (heterozygous carriers), we determined radiation-induced leukocyte apoptosis using flow cytometry. As TP53 gene is involved in the control of apoptosis, we studied its status in FA lymphocytes using dual colour fluorescence in situ hybridization (FISH). FA patients and female heterozygous carriers display radiosensitive response to ionizing radiation seen as abnormal elimination of cells via apoptosis. By employment of FISH, the TP53 allele loss in FA lymphocytes was not observed. In diseases related to oxidative stress, determination of radiation-induced apoptosis is the method of choice for testing the radiosensitivity. (author)

  13. Radioisotopic 51Cr-leukocyte adherence inhibition (LAI) assay. I

    International Nuclear Information System (INIS)

    Tsang, P.H.; Tangnavarad, K.; Lesnick, G.; Holland, J.F.; Bekesi, J.G.; Perloff, M.

    1980-01-01

    A simplified radioisotopic leukocyte adherence inhibition assay ( 51 Cr-LAI assay) was used to determine tumor-directed immune responses in patients with cancer of the breast. Essential steps in development of this assay are the standardization of conditions for optimal 51 Cr uptake by peripheral blood lymphocytes (PBL) and the inclusion of autologous or normal AB serum in the incubation media. A dextrose salt mixture (GNK) was found to enhance intracellular uptake of 51 Cr significantly (8-fold) without affecting viability of the cells or without causing selective loss of lymphocyte subpopulations. The presence of 10% autologous or normal AB serum prevented non-specific LAI responses to unrelated tumor antigens. Experimental results are presented and it is seen that this short term (4 h) 51 Cr-LAI assay provides reproducible and specific results analogous to those using tube-LAI assay. The test has the advantages of being accurate, sensitive and free from technical bias. (Auth.)

  14. Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

    Energy Technology Data Exchange (ETDEWEB)

    Fell, A.H.; Preston, P.M. (Edinburgh Univ. (United Kingdom))

    1992-07-01

    Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author).

  15. Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

    International Nuclear Information System (INIS)

    Fell, A.H.; Preston, P.M.

    1992-01-01

    Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author)

  16. Carp macrophages and neutrophilic granulocytes secrete an interleukin-1-like factor.

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Weyts, F.A.A.; Debets, R.; Flik, G.

    1995-01-01

    Carp, Cyprinus carpio L, macrophages and neutrophilic granulocytes obtained from pronephros were cultured. Supernatant was harvested after 48 h and tested for interleukin-1 (IL-1) bioactivity. A concentration-dependent stimulation of proliferation was found of carp Ig− lymphocytes as well as of the

  17. Biotransformation of arachidonic acid (AA) and eicosapentaenoic acid (EPA) into lipoxins and lipoxenes by porcine leukocytes

    International Nuclear Information System (INIS)

    Wong, P.Y.K.; Spur, B.; Hirai, A.; Yoshida, S.; Tamura, Y.; Lam, B.K.

    1986-01-01

    Lipoxins and lipoxenes have been reported to be formed after incubation of 15-hydroperoxyeicosatetraenoic acid and 15-hydroperoxyeicosapentaenoic acid with human leukocytes and porcine leukocytes, respectively. The authors examined the ability of porcine leukocytes to metabolize [ 14 C]-AA and [ 14 C]-EPA (100 μM) to lipoxins and lipoxenes. Incubation products were separated by RP-HPLC and identified by U.V. spectrum and GC/MS. Porcine leukocytes metabolized both AA and EPA to form lipoxins and lipoxenes in addition to mono- and di-hydroxyl fatty acids. Quantitative analysis from U.V. absorbance after RP-HPLC revealed that about 0.05% of AA was converted to lipoxins A and B and 0.1% of EPA was converted to lipoxenes A and B. In addition, treatment of leukotriene A 4 and leukotriene A 5 with 15-lipoxygenase also gave rise to several isomers of lipoxin and lipoxene. Thus, lipoxins and lipoxenes would have been derived from AA and EPA after dioxygenation by 5-lipoxygenase and 15-lipoxygenase, respectively. When tested for biological activity, lipoxene A (2 μM), like lipoxin A, induced superoxide anion generation in canine neutrophils but had no effect on lysosomal enzyme release on neutrophil aggregation

  18. Induction of expression of iNOS by N-nitrosodimethylamine (NDMA) in human leukocytes.

    Science.gov (United States)

    Ratajczak-Wrona, Wioletta; Jablonska, Ewa; Jablonski, Jakub; Marcinczyk, Magdalena

    2009-01-01

    The aim of this study was to assess the influence of N-nitrosodimethylamine (NDMA) on expression of inducible nitric oxide synthase (iNOS), as well as production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by human neutrophils (PMN) and peripheral blood mononuclear cells (PBMC), and the participation of the p38 MAPK kinase in this process. Furthermore, the ability of neutrophils to release superoxide anion was determined. The influence of N-nitrosodimethylamine on iNOS expression was determined in isolated PMN and PBMC cells from peripheral blood of healthy individuals. The mononuclear cells showed higher sensitivity to NDMA. Moreover, cytotoxic effect of NDMA can be influenced in some way by the impact of this xenobiotic on nitric oxide and superoxide anion release from human leukocytes. Furthermore, increased generation of these radicals by human leukocytes suggest that neutrophils and mononuclear cells that are exposed to NDMA activity can play a key role in endogenous NDMA generation. However the relationship between iNOS expression and phospho-p38 MAPK in neutrophils and mononuclear cells shows that p38 MAPK pathway participates in induction of iNOS expression in the presence of NDMA.

  19. Immunosenescence of Polymorphonuclear Neutrophils

    Directory of Open Access Journals (Sweden)

    Inga Wessels

    2010-01-01

    Full Text Available All immune cells are affected by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. The effect of aging on cells of the adaptive immune system is well documented. In contrast, knowledge concerning age-related defects of polymorphonuclear neutrophils (PMN is limited. During the past decade, it has become evident that in addition to their traditional role as phagocytes, neutrophils are able to secrete a wide array of immunomodulating molecules. Their importance is underlined by the finding that genetic defects that lead to neutropenia increase susceptibility to infections. Whereas there is consistence about the constant circulating number of PMN throughout aging, the abilities of tissue infiltration, phagocytosis, and oxidative burst of PMN from aged donors are discussed controversially. Furthermore, there are numerous discrepancies between in vivo and in vitro results, as well as between results for murine and human PMN. Most of the reported functional changes can be explained by defective signaling pathways, but further research is required to get a detailed insight into the underlying molecular mechanisms. This could form the basis for drug development in order to prevent or treat age-related diseases, and thus to unburden the public health systems.

  20. Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

    Directory of Open Access Journals (Sweden)

    Yutaro Shiota

    2000-01-01

    Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

  1. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.

    Science.gov (United States)

    Hidalgo, Andrés; Peired, Anna J; Wild, Martin; Vestweber, Dietmar; Frenette, Paul S

    2007-04-01

    The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro, but the complete identification of its physiological ligands has remained elusive. Here, we showed that E-selectin ligand-1 (ESL-1), P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin ligand activity on neutrophils by using gene- and RNA-targeted loss of function. PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was critical for converting initial tethers into steady slow rolling. CD44 controlled rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling.

  2. Effect of induced subclinical hypocalcemia on physiological responses and neutrophil function in dairy cows.

    Science.gov (United States)

    Martinez, N; Sinedino, L D P; Bisinotto, R S; Ribeiro, E S; Gomes, G C; Lima, F S; Greco, L F; Risco, C A; Galvão, K N; Taylor-Rodriguez, D; Driver, J P; Thatcher, W W; Santos, J E P

    2014-02-01

    The objectives were to study the effects of induced subclinical hypocalcemia [SCH, blood ionized Ca (iCa(2+)) dairy cows. Ten nonpregnant, nonlactating Holstein cows were blocked by lactation and assigned randomly to a normocalcemic (NC; intravenous infusion of 0.9% NaCl i.v. plus 43 g of oral Ca, as Ca sulfate and Ca chloride, at -1 and 11h) or an induced SCH [SCHI, 5% ethylene glycol tetraacetic acid (EGTA), a selective iCa(2+) chelator, intravenous infusion] treatment for 24h, using a crossover design. The sequence of treatments was either NC-SCHI or SCHI-NC, with a 6-d washout period. Ionized Ca was evaluated before, hourly during the infusion period, and at 48 and 72 h, to monitor concentrations and adjust the rate of infusion, maintaining blood iCa(2+) insulin in plasma, and urinary excretion of Ca. Total and differential leukocyte count in blood was also performed. The concentration of cytosolic iCa(2+) in neutrophils and lymphocytes was quantified and neutrophil function was assayed in vitro. Infusion of a 5% EGTA solution successfully induced SCH in all SCHI cows, resulting in decreased blood iCa(2+) concentrations throughout the 24-h treatment period (0.77 ± 0.01 vs. 1.26 ± 0.01 mM iCa(2+)). Induction of SCH reduced dry matter intake on the day of infusion (5.3 ± 0.8 vs. 9.1 ± 0.8 kg/d) and rumen contractions (1.9 ± 0.2 vs. 2.7 ± 0.2 contractions/2 min) for the last 12h of infusion. Cows in SCHI had decreased plasma insulin concentration (1.44 ± 0.23 vs. 2.32 ± 0.23 ng/mL) evident between 6 and 18 h after the beginning of the infusion, accompanied by increased concentrations of glucose (4.40 ± 0.04 vs. 4.17 ± 0.04 mM). Plasma nonesterified fatty acids concentration was greater for SCHI than NC cows (0.110 ± 0.019 vs. 0.061 ± 0.014 mM). Neutrophils of cows in SCHI had a faster decrease in cytosolic iCa(2+) after stimulation with ionomycin (9.9 ± 1.0 vs. 13.6 ± 1.4 Fluo-4:Fura Red post-end ratio) in vitro. Furthermore, induction of SCH reduced

  3. Spontaneous neutrophil activation in HTLV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Jaqueline B. Guerreiro

    Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

  4. Ensemble models of neutrophil trafficking in severe sepsis.

    Directory of Open Access Journals (Sweden)

    Sang Ok Song

    Full Text Available A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental

  5. Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Samantha P Tull

    2009-08-01

    Full Text Available Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA, arachidonic acid, into the eicosanoid prostaglandin-D(2 (PGD(2 by cyclooxygenase (COX enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA, was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3. This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2 receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2 signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not

  6. Targeting neutrophilic inflammation in severe neutrophilic asthma : can we target the disease-relevant neutrophil phenotype?

    NARCIS (Netherlands)

    Bruijnzeel, Piet L B; Uddin, Mohib; Koenderman, Leo

    2015-01-01

    In severe, neutrophilic asthma, neutrophils are thought to have an important role in both the maintenance of the disease and during exacerbations. These patients often display excessive, mucosal airway inflammation with unresolving neutrophilia. Because this variant of asthma is poorly controlled by

  7. Antagonism of CD11b with neutrophil inhibitory factor (NIF inhibits vascular lesions in diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Alexander A Veenstra

    Full Text Available Leukocytes and proteins that govern leukocyte adhesion to endothelial cells play a causal role in retinal abnormalities characteristic of the early stages of diabetic retinopathy, including diabetes-induced degeneration of retinal capillaries. Leukocyte integrin αmβ2 (CD11b/CD18, MAC1, a protein mediating adhesion, has been shown to mediate damage to endothelial cells by activated leukocytes in vitro. We hypothesized that Neutrophil Inhibitory Factor (NIF, a selective antagonist of integrin αmβ2, would inhibit the diabetes-induced degeneration of retinal capillaries by inhibiting the excessive interaction between leukocytes and retinal endothelial cells in diabetes. Wild type animals and transgenic animals expressing NIF were made diabetic with streptozotocin and assessed for diabetes-induced retinal vascular abnormalities and leukocyte activation. To assess if the leukocyte blocking therapy compromised the immune system, animals were challenged with bacteria. Retinal superoxide production, leukostasis and leukocyte superoxide production were increased in wild type mice diabetic for 10 weeks, as was the ability of leukocytes isolated from diabetic animals to kill retinal endothelial cells in vitro. Retinal capillary degeneration was significantly increased in wild type mice diabetic 40 weeks. In contrast, mice expressing NIF did not develop any of these abnormalities, with the exception that non-diabetic and diabetic mice expressing NIF generated greater amounts of superoxide than did similar mice not expressing NIF. Importantly, NIF did not significantly impair the ability of mice to clear an opportunistic bacterial challenge, suggesting that NIF did not compromise immune surveillance. We conclude that antagonism of CD11b (integrin αmβ2 by NIF is sufficient to inhibit early stages of diabetic retinopathy, while not compromising the basic immune response.

  8. Antagonism of CD11b with neutrophil inhibitory factor (NIF) inhibits vascular lesions in diabetic retinopathy.

    Science.gov (United States)

    Veenstra, Alexander A; Tang, Jie; Kern, Timothy S

    2013-01-01

    Leukocytes and proteins that govern leukocyte adhesion to endothelial cells play a causal role in retinal abnormalities characteristic of the early stages of diabetic retinopathy, including diabetes-induced degeneration of retinal capillaries. Leukocyte integrin αmβ2 (CD11b/CD18, MAC1), a protein mediating adhesion, has been shown to mediate damage to endothelial cells by activated leukocytes in vitro. We hypothesized that Neutrophil Inhibitory Factor (NIF), a selective antagonist of integrin αmβ2, would inhibit the diabetes-induced degeneration of retinal capillaries by inhibiting the excessive interaction between leukocytes and retinal endothelial cells in diabetes. Wild type animals and transgenic animals expressing NIF were made diabetic with streptozotocin and assessed for diabetes-induced retinal vascular abnormalities and leukocyte activation. To assess if the leukocyte blocking therapy compromised the immune system, animals were challenged with bacteria. Retinal superoxide production, leukostasis and leukocyte superoxide production were increased in wild type mice diabetic for 10 weeks, as was the ability of leukocytes isolated from diabetic animals to kill retinal endothelial cells in vitro. Retinal capillary degeneration was significantly increased in wild type mice diabetic 40 weeks. In contrast, mice expressing NIF did not develop any of these abnormalities, with the exception that non-diabetic and diabetic mice expressing NIF generated greater amounts of superoxide than did similar mice not expressing NIF. Importantly, NIF did not significantly impair the ability of mice to clear an opportunistic bacterial challenge, suggesting that NIF did not compromise immune surveillance. We conclude that antagonism of CD11b (integrin αmβ2) by NIF is sufficient to inhibit early stages of diabetic retinopathy, while not compromising the basic immune response.

  9. Significance of the neutrophil-lymphocyte ratio in elderly type 2 diabetic patients with coronary heart disease%老年2型糖尿病并发冠心病患者血中性粒细胞与淋巴细胞比值的变化及意义

    Institute of Scientific and Technical Information of China (English)

    何茜; 谭洪文; 于瑞萍; 罗建华; 徐淑静

    2016-01-01

    目的 探讨老年2型糖尿病并发冠心病患者血中性粒细胞与淋巴细胞比值(NLR)的变化及意义. 方法 采用回顾性病例分析方法,收集2014年4月至2015年7月在贵州省人民医院心内科行冠状动脉造影的老年患者228例,其中糖尿病组77例、冠心病组72例和糖尿病+冠心病组79例,另选70例老年健康体检者为对照组,检测各组白细胞计数、超敏C反应蛋白(hs-CRP)等指标,并计算NLR.Logistic回归分析糖尿病并发冠心病的危险因素,多元逐步回归分析NLR的影响因素. 结果 糖尿病组、冠心病组及糖尿病+冠心病组与对照组比较,白细胞计数[(7.48±1.81)×109/L、(7.72±1.89)×109/L、(7.98±2.12)×109/L与(6.22±1.61)×109/L]、中性粒细胞计数[(4.49±1.38)×109/L、(4.88±1.56)×109/L、(5.35±1.40)×109/L与(3.52±0.84)×109/L]、NLR(2.84±0.77、3.07±0.79、3.34±0.83与1.58±0.42)、hs-CRP[(2.92±0.65) mg/L、(3.20±0.86) mg/L、(4.98±1.10) mg/L与(1.15±0.23)mg/L],均明显升高(P<0.05或P<0.01);淋巴细胞计数降低[(1.57±0.41)×109/L、(1.58±0.40)×109/L、(1.61±0.48)×109/L与(2.22±0.51)×109/L,P<0.05];糖尿病+冠心病组NLR、hs-CRP高于糖尿病组和冠心病组(P<0.05).Pearson相关分析显示,NLR与Gensini积分、hs-CRP正相关(r值分别为0.7455、0.7792,P<0.01).Logistic回归分析显示,NLR、hs-CRP、糖化血红蛋白(HbA1c)是糖尿病并发冠心病的危险因素(OR值分别为4.331、3.997、2.928,P<0.05).多元逐步回归分析显示,NLR与空腹血糖、HbA1c、收缩压正相关(标准化回归系数分别为0.3133、0.4720、0.3069,P<0.05). 结论 NLR可能是老年糖尿病患者并发冠心病的一个较好预测指标.%Objective To evaluate the value of the neutrophil-lymphocyte ratio (NLR) in elderly type 2 diabetic patients (T2DM) with coronary heart disease (CHD).Methods We performed a retrospective observational study on 228 patients undergoing coronary angiography in Guizhou

  10. Effectiveness of leukocyte immunotherapy in primary recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Gharesi-Fard, Behrouz; Zolghadri, Jaleh; Foroughinia, Leila; Tavazoo, Fahimeh; Samsami Dehaghani, Alamtaj

    2007-09-01

    Recurrent spontaneous abortion (RSA) is defined as three or more sequential abortions before the twentieth week of gestation. There are evidences to support an allo-immunologic mechanism for RSA. One of the methods for treatment of RSA is leukocyte therapy; however there is still controversy about effectiveness of this method. To evaluate the effectiveness of leukocyte therapy for treatment of RSA. Ninety two non-pregnant women with at least three sequential abortions (60 primary & 32 secondary aborters) recognized as RSA were referred to our Laboratory for immunotherapy. All the cases were immunized by isolated lymphocytes from their husbands. Fifty to 100 million washed and resuspended mononuclear cells were injected by I.V., S.C., and I.D. route. The result of each injection was checked by WBC cross matching between couples after four weeks of injections. Immunization was repeated in fifth week to a maximum of 3 times if needed. Eighty one age-matched non-pregnant RSA women (52 primary and 29 secondary aborters) with at least three sequential abortions were also included in this study as controls. The control group was not immunized. 67 out of 92 (72.8%) immunized cases and 44 out of 81 controls (54.3%) showed a successful outcome of pregnancy (pRSA patients. Despite the current controversy and limitation of leukocyte therapy in RSA, the results of our investigation provide evidence supporting the use of allo-immunization in improving the outcome of pregnancy in primary RSA patients.

  11. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

    Science.gov (United States)

    Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

    2017-11-01

    Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

  12. 5-Lipoxygenase-Dependent Recruitment of Neutrophils and Macrophages by Eotaxin-Stimulated Murine Eosinophils

    Directory of Open Access Journals (Sweden)

    Ricardo Alves Luz

    2014-01-01

    Full Text Available The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LTB4, a 5-lipoxygenase (5-LO metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1 were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

  13. Role of β1 integrins and bacterial adhesins for Yop injection into leukocytes in Yersinia enterocolitica systemic mouse infection.

    Science.gov (United States)

    Deuschle, Eva; Keller, Birgit; Siegfried, Alexandra; Manncke, Birgit; Spaeth, Tanja; Köberle, Martin; Drechsler-Hake, Doreen; Reber, Julia; Böttcher, Ralph T; Autenrieth, Stella E; Autenrieth, Ingo B; Bohn, Erwin; Schütz, Monika

    2016-02-01

    Injection of Yersinia outer proteins (Yops) into host cells by a type III secretion system is an important immune evasion mechanism of Yersinia enterocolitica (Ye). In this process Ye invasin (Inv) binds directly while Yersinia adhesin A (YadA) binds indirectly via extracellular matrix (ECM) proteins to β1 integrins on host cells. Although leukocytes turned out to be an important target of Yop injection by Ye, it was unclear which Ye adhesins and which leukocyte receptors are required for Yop injection. To explain this, we investigated the role of YadA, Inv and β1 integrins for Yop injection into leukocytes and their impact on the course of systemic Ye infection in mice. Ex vivo infection experiments revealed that adhesion of Ye via Inv or YadA is sufficient to promote Yop injection into leukocytes as revealed by a β-lactamase reporter assay. Serum factors inhibit YadA- but not Inv-mediated Yop injection into B and T cells, shifting YadA-mediated Yop injection in the direction of neutrophils and other myeloid cells. Systemic Ye mouse infection experiments demonstrated that YadA is essential for Ye virulence and Yop injection into leukocytes, while Inv is dispensable for virulence and plays only a transient and minor role for Yop injection in the early phase of infection. Ye infection of mice with β1 integrin-depleted leukocytes demonstrated that β1 integrins are dispensable for YadA-mediated Yop injection into leukocytes, but contribute to Inv-mediated Yop injection. Despite reduced Yop injection into leukocytes, β1 integrin-deficient mice exhibited an increased susceptibility for Ye infection, suggesting an important role of β1 integrins in immune defense against Ye. This study demonstrates that Yop injection into leukocytes by Ye is largely mediated by YadA exploiting, as yet unknown, leukocyte receptors. Copyright © 2015. Published by Elsevier GmbH.

  14. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    International Nuclear Information System (INIS)

    Aitken, R.; Coulson, P.S.; Wilson, R.A.

    1988-01-01

    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means

  15. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

    LENUS (Irish Health Repository)

    Hong, Ying

    2012-01-01

    The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.

  16. Photoperiod affects the expression of sex and species differences in leukocyte number and leukocyte trafficking in congeneric hamsters.

    Science.gov (United States)

    Bilbo, S D; Dhabhar, F S; Viswanathan, K; Saul, A; Nelson, R J

    2003-11-01

    Sex differences in immune function are well documented. These sex differences may be modulated by social and environmental factors. Individuals of polygynous species generally exhibit more pronounced sex differences in immune parameters than individuals of monogamous species, often displaying an energetic trade-off between enhanced immunity and high mating success. During winter, animals contend with environmental conditions (e.g. low temperatures and decreased food availability) that evoke energetic-stress responses; many mammals restrict reproduction in response to photoperiod as part of an annual winter coping strategy. To test the hypothesis that extant sex and species differences in immune surveillance may be modulated by photoperiod, we examined leukocyte numbers in males and females of two closely related hamster species (Phodopus). As predicted, uniparental P. sungorus exhibited a robust sex difference, with total white blood cells, total lymphocytes, T cells, and B cells higher in females than males, during long days when reproduction occurs, but not during short days when reproduction usually stops. In contrast, biparental male and female P. campbelli exhibited comparable leukocyte numbers during both long and short days. To study sex differences in stress responses, we also examined immune cell trafficking in response to an acute (2 h) restraint stressor. During stressful challenges, it appears beneficial for immune cells to exit the blood and move to primary immune defense areas such as the skin, in preparation for potential injury or infection. Acute stress moved lymphocytes and monocytes out of the blood in all animals. Blood cortisol concentrations were increased in P. sungorus females compared to males at baseline (52%) and in response to restraint stress (38%), but only in long days. P. campbelli males and females exhibited comparable blood cortisol and stress responses during both long and short days. Our results suggest that interactions among

  17. Neutrophil programming dynamics and its disease relevance.

    Science.gov (United States)

    Ran, Taojing; Geng, Shuo; Li, Liwu

    2017-11-01

    Neutrophils are traditionally considered as first responders to infection and provide antimicrobial host defense. However, recent advances indicate that neutrophils are also critically involved in the modulation of host immune environments by dynamically adopting distinct functional states. Functionally diverse neutrophil subsets are increasingly recognized as critical components mediating host pathophysiology. Despite its emerging significance, molecular mechanisms as well as functional relevance of dynamically programmed neutrophils remain to be better defined. The increasing complexity of neutrophil functions may require integrative studies that address programming dynamics of neutrophils and their pathophysiological relevance. This review aims to provide an update on the emerging topics of neutrophil programming dynamics as well as their functional relevance in diseases.

  18. Ovine leukocyte profiles do not associate with variation in the prion gene, but are breed-dependent

    Science.gov (United States)

    Prion genotype in sheep confer resistance to scrapie. In cattle, lymphocyte profile has been found to be associated with prion genotype. Therefore, the aim of this study was to determine if variations in the sheep prion gene were associated with leukocyte populations as measured by complete blood ce...

  19. Dihydroxyoctadecamonoenoate esters inhibit the neutrophil ...

    Indian Academy of Sciences (India)

    PRAKASH

    that observed with arachidonic acid treatment (Li et al 1996). ..... An alternative possibility is that the methyl DiHOMEs .... nitric oxide-derived reactive species in vascular cells; Circ. ... necrosis factor 1-alpha-initiated neutrophil responses and.

  20. Leukocyte count, systemic inflammation, and health status in older adults: a narrative review

    Directory of Open Access Journals (Sweden)

    Chmielewski Piotr

    2018-03-01

    Full Text Available Epidemiological and clinical studies suggest that elevated leukocyte count within the normal range can predict cardiovascular and total mortality in older adults. These findings are remarkable because this simple and common laboratory test is included in routine medical check-ups. It is well known that chronic systemic inflammation (inflammaging is one of the hallmarks of aging and an important component of obesity-associated insulin resistance that can lead to type 2 diabetes and other health problems in both overweight individuals and elderly people. To understand the molecular mechanisms linking increased systemic inflammation with aging-associated diseases and elevated leukocyte counts in the elderly is to unravel the multiplicity of molecular factors and mechanisms involved in chronic low-grade systemic inflammation, the gradual accumulation of random molecular damage, age-related diseases, and the process of leukopoiesis. There are several possible mechanisms through which chronic low-grade systemic inflammation is associated with both higher leukocyte count and a greater risk of aging-associated conditions in older adults. For example, the IL-6 centric model predicts that this biomediator is involved in chronic systemic inflammation and leukopoiesis, thereby suggesting that elevated leukocyte count is a signal of poor health in older adults. Alternatively, an increase in neutrophil and monocyte counts can be a direct cause of cardiovascular events in the elderly. Interestingly, some authors assert that the predictive ability of elevated leukocyte counts with regard to cardiovascular and allcause mortality among older adults surpass the predictive value of total cholesterol. This review reports the recent findings on the links between elevated but normal leukocyte counts and the increased risks of all-cause, cardiovascular, and cancer mortality. The possible molecular mechanisms linking higher but normal leukocyte counts with increased

  1. Variation in sister chromatid exchange frequencies between human and pig whole blood, plasma leukocyte, and mononuclear leukocyte cultures

    International Nuclear Information System (INIS)

    Larramendy, M.L.; Reigosa, M.A.

    1986-01-01

    Sister chromatid exchange (SCE) induction by ultraviolet (UV) light was studied in both human and pig whole blood cultures (WBC) and plasma leukocyte cultures (PLC). No variation in SCE frequency was observed between pig WBC and PLC in control as well as in treated cells. Conversely, SCE frequencies of human PLC were consistently higher than those of WBC in control and UV-exposed cells. Thus, red blood cells (RBCs) do not influence the sensitivity of lymphocytes to UV LIGHT exposure, and there must be some different culture condition(s) in the inducation of SCEs between human WBC and PLC but not in swine lymphocyte cultures. Since the BrdUrd/lymphocyte ratio of WBC was halved in PLC, the effect of BrdUrd concentration in inducing the SCE baseline frequency of PLC may be ruled out. Neither the cell separation technique nor polymorphonuclear leukocytes had a significant role in the elevated SCE frequency of human PLC or MLC. Experiments where human RBCs were titrated into human PLC showed that the induction of an elevated SCE frequency of PLC was suppressed in a dose-dependent manner by the presence of RBCs in the culture medium. Since the incorporation of pig or human RBCs into human PLC as well as into MLC reduced the SCE frequency to that of WBC, a common component and/or function existing in these cells is suggested. Analysis of different RBC components showed that RBCs, specifically RBC ghosts, release a diffusible but not dialyzable corrective factor into culture medium that is able to reduce the SCE frequencies of PLC

  2. The history of fever, leukocytic pyrogen and interleukin-1.

    Science.gov (United States)

    Dinarello, Charles A

    2015-01-01

    There has been great progress in the 30 y since the reporting in 1984 of the cDNA for interleukin1 (IL1) β in the human and IL1α in the mouse. However, the history of IL1 begins in the early 1940s with investigations into the nature of an endogenous fever-producing protein released rabbit peritoneal neutrophils. Most researchers in immunology today are unaware that the field of cytokines, particularly the field of inflammatory cytokines. Toll-like receptors and innate immunity traces back to studies on fever. Researchers in infectious diseases wanted to know about an endogenous protein that caused fever, independent of infection. The endogenous fever-producing protein was called by various names: granulocyte, endogenous or leukocytic pyrogen. It is a fascinating and sometimes controversial story for biology and medicine and for the treatment of inflammatory diseases. Few imagined that this fever-producing protein would play such a major role in nearly every cell and in most diseases. This paper reviews the true background and milestones of interleukin1 from the purification of leukocytic pyrogen to the first cDNA of IL1β and the validation of cytokine biology from ill-defined factors to its present day importance.

  3. Role of bacteria in leukocyte adhesion deficiency-associated periodontitis.

    Science.gov (United States)

    Hajishengallis, George; Moutsopoulos, Niki M

    2016-05-01

    Leukocyte adhesion deficiency Type I (LAD-I)-associated periodontitis is an aggressive form of inflammatory bone loss that has been historically attributed to lack of neutrophil surveillance of the periodontal infection. However, this form of periodontitis has proven unresponsive to antibiotics and/or mechanical removal of the tooth-associated biofilm. Recent studies in LAD-I patients and relevant animal models have shown that the fundamental cause of LAD-I periodontitis involves dysregulation of a granulopoietic cytokine cascade. This cascade includes interleukin IL-23 (IL-23) and IL-17 that drive inflammatory bone loss in LAD-I patients and animal models and, moreover, foster a nutritionally favorable environment for bacterial growth and development of a compositionally unique microbiome. Although the lack of neutrophil surveillance in the periodontal pockets might be expected to lead to uncontrolled bacterial invasion of the underlying connective tissue, microbiological analyses of gingival biopsies from LAD-I patients did not reveal tissue-invasive infection. However, bacterial lipopolysaccharide was shown to translocate into the lesions of LAD-I periodontitis. It is concluded that the bacteria serve as initial triggers for local immunopathology through translocation of bacterial products into the underlying tissues where they unleash the dysregulated IL-23-IL-17 axis. Subsequently, the IL-23/IL-17 inflammatory response sustains and shapes a unique local microbiome which, in turn, can further exacerbate inflammation and bone loss in the susceptible host. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts

    International Nuclear Information System (INIS)

    Hand, W.L.; King-Thompson, N.L.

    1990-01-01

    Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat less than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes

  5. Leukocyte Reference Intervals for Free-Ranging Hummingbirds in Northern California.

    Science.gov (United States)

    Safra, Noa; Christopher, Mary M; Ernest, Holly B; Bandivadekar, Ruta; Tell, Lisa A

    2018-04-04

      Hummingbirds are specialized nectarivores and important ecological pollinators that are the focus of conservation efforts as well as scientific investigations of metabolism and flight dynamics. Despite their importance, basic information is lacking about hummingbird blood cells. We aimed to establish reference intervals for total and differential leukocyte counts from healthy free-ranging hummingbirds in northern California. Hummingbirds were captured in five counties in spring and summer of 2012. A drop of blood was used to prepare smears for total white blood cell estimate and 200-cell differential leukocyte counts. Reference Value Advisor was used for descriptive statistics and calculation of reference intervals. Blood smears from 42 Anna's Hummingbirds ( Calypte anna) and 33 Black-chinned Hummingbirds ( Archilochus alexandri) were included. The only significant differences in leukocyte counts were due to age, and juvenile hummingbirds had significantly higher lymphocyte counts than adult hummingbirds ( Phummingbirds.

  6. Chemotaxis of nurse shark leukocytes.

    Science.gov (United States)

    Obenauf, S D; Smith, S H

    1985-01-01

    Studies were conducted to determine the ability of leukocytes from the nurse shark to migrate in an in vitro micropore filter chemotaxis assay and to determine optimal assay conditions and suitable attractants for such an assay. A migratory response was seen with several attractants: activated rat serum, activated shark plasma, and a pool of shark complement components. Only the response to activated rat serum was chemotactic, as determined by the checkerboard assay.

  7. Interleukin-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

    Science.gov (United States)

    Liu, Rebecca; Lauridsen, Holly M.; Amezquita, Robert A.; Pierce, Richard W.; Jane-wit, Dan; Fang, Caodi; Pellowe, Amanda S.; Kirkiles-Smith, Nancy C.; Gonzalez, Anjelica L.; Pober, Jordan S.

    2016-01-01

    A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space. PMID:27534549

  8. Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.

    Directory of Open Access Journals (Sweden)

    Carlos Alfaro

    Full Text Available Dendritic cells (DC are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs as a result of being co-attracted by interleukin-8 (IL-8, for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA protein, were able to cross-present the antigen to CD8 (OT-1 and CD4 (OT-2 TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2(d mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2(d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2(b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2(d are coinjected in the footpad of mice with autologous DC (H-2(b. In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC.

  9. [Reference values of neonatal erythrocyte and leukocyte count in Bamako, Mali].

    Science.gov (United States)

    Diallo, Dapa Aly; Diawara, Faoumata; Guindo, Aldiouma; Touré, Moustaph; Traoré, Mamadou; Fofana, Aïssata Traoré; Dembélé, Albdoul K; Guindo, Agnès; Diallo, Yacouba Lazare; Diallo, Oumahane; Baraika, Ag Mohamed; Dolo, Amadou Ingré

    2013-01-01

    Reference values for blood cell count are not established at birth in Mali. This study aimed to determine reference values for erythrocyte and leukocyte at birth in Bamako. Blood was collected from the umbilical cord immediately following its clamping and studied for complete blood cell count in 481 newborns with a birth weight > 2500g, Apgar score ≤ 7 at 5 or 10 minutes, without abnormal hemoglobin mutations and whose mothers were willing in Bamako, Mali. Other than the median and mean values, 2.5 and 97.5 percentiles were calculated. The findings suggest that the normal reference values following a timely clamping of the umbilical cord were (mean ± 1SD and range): RBC = 4,00 ± 0,46.1012/L (3,13 - 4,89), Hb = 14,12 ± 1,49 g/dL (11,20 - 17,00), Hct = 40,27 ± 4,71% (31,62 - 50,18), MCV = 101 ± 5 fl (91 - 112), MCHC = 35,37 ± 2,16 pg/cellule (30,70 - 39,59), MCH = 35,06 ± 0,93 g/dL (33,40 - 36,90), RDW = 17,79 ± 7,33% (15,50 - 20,39), Reticulocytes (109/L) = 133,081 ± 29,95 (66,62 - 200,86), GB (109/L) = 13,24 ± 7,23 (7,20 - 23,70), PMN (109/L) = 7,16 ± 4,70 (3,07 - 14,22), PME (109/L) = 0,28 ± 0,26 (0 - 0,98), PMB(109/L) = 0,05 ± 0,09 (0 - 0,31), Lymphocytes (109/L) = 4,49 ± 2,45 (1,96 - 9,42), Monocytes (10 9 /L) = 1,06 ± 0,73 (0,21 - 2,54), myelocytes = 1.43 ± 1.51%, erythroblasts = 4.52 ± 7.83%. It should be noted that male babies had a lower neutrophil count than female newborns. By taking into account these results when interpreting the blood cell count in Malian newborn infants, costly misdiagnoses should be considerably decreased in a population struggling with low incomes. Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.

  10. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Caroline Boda

    Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

  11. Chronic lymphocytic leukemia (CLL)

    Science.gov (United States)

    ... is used for painful and enlarged lymph nodes. Blood transfusions or platelet transfusions may be required if blood ... unexplained fatigue, bruising, excessive sweating, or weight loss. Alternative ... Leukemia - chronic lymphocytic (CLL); Blood cancer - chronic lymphocytic leukemia; Bone marrow cancer - chronic ...

  12. In vitro interactions of lymphocytes and cultured cells from beagles with plutonium-induced bone tumors

    International Nuclear Information System (INIS)

    Frazier, M.E.; Lund, J.E.; Busch, R.H.

    1976-01-01

    Cell cultures have been prepared from lung and bone tumors arising in beagle dogs following exposure to inhaled plutonium. Evaluation of the cultured cells by commonly applied criteria (i.e., cell morphology, lack of contact inhibitory mechanisms, cloning efficiency, growth in soft agar, and tumor production in vivo) indicated that tumor cells were being grown in culture. Blood leukocytes and peripheral lymphocytes from beagle dogs were tested for cytotoxic effects against several cell cultures. Lymphocytes from normal dogs or dogs with unrelated tumors would not kill the bone tumor cells unless monocytes (macrophage) were present, in which case the leukocyte preparation was capable of mounting de novo cytotoxic immune reactions after 3 to 5 days in culture. In contrast, the dogs with plutonium-induced bone tumors had circulating lymphocytes that appeared to have undergone presensitization to bone-tumor-distinctive antigens in vivo. Consequently these lymphocytes interacted with cultured cells promptly after encounter in vitro

  13. Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2011-01-01

    Full Text Available Leukocyte adhesion to the vascular endothelium and subsequent transendothelial migration play essential roles in the pathogenesis of cardiovascular diseases such as atherosclerosis. The leukocyte adhesion is mediated by localized activation of the endothelium through the action of inflammatory cytokines. The exact proinflammatory factors, however, that activate the endothelium and their cellular sources remain incompletely defined.Using bone marrow-derived mast cells from wild-type, Tnf(-/-, Ifng(-/-, Il6(-/- mice, we demonstrated that all three of these pro-inflammatory cytokines from mast cells induced the expression of vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1, P-selectin, and E-selectin in murine heart endothelial cells (MHEC at both mRNA and protein levels. Compared with TNF-α and IL6, IFN-γ appeared weaker in the induction of the mRNA levels, but at protein levels, both IL6 and IFN-γ were weaker inducers than TNF-α. Under physiological shear flow conditions, mast cell-derived TNF-α and IL6 were more potent than IFN-γ in activating MHEC and in promoting neutrophil adhesion. Similar observations were made when neutrophils or macrophages were used. Neutrophils and macrophages produced the same sets of pro-inflammatory cytokines as did mast cells to induce MHEC adhesion molecule expression, with the exception that macrophage-derived IFN-γ showed negligible effect in inducing VCAM-1 expression in MHEC.Mast cells, neutrophils, and macrophages release pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL6 that induce expression of adhesion molecules in endothelium and recruit of leukocytes, which is essential to the pathogenesis of vascular inflammatory diseases.

  14. Mechanisms of the priming effect of low doses of lipopoly-saccharides on leukocyte-dependent platelet aggregation in whole blood.

    Science.gov (United States)

    Montrucchio, Giuseppe; Bosco, Ornella; Del Sorbo, Lorenzo; Fascio Pecetto, Paolo; Lupia, Enrico; Goffi, Alberto; Omedè, Paola; Emanuelli, Giorgio; Camussi, Giovanni

    2003-11-01

    Several studies focused on the ability of bacterial lipopolysac-charides (LPS) in triggering platelet and/or leukocyte activation. The aim of this study was to investigate the molecular mechanisms involved in the aggregation of platelets and in their interaction with leukocytes in whole blood after stimulation with low doses of LPS. LPS did not directly induce platelet aggregation in whole blood, but they primed the aggregation of platelets induced by epinephrine, adenosine diphosphate and arachidonic acid. As shown by cytofluorimetry, platelets neither bind FITC-LPS, nor express the LPS-receptors CD14 and toll-like receptor 4 (TLR4). On the contrary, LPS primed monocytes and to a lesser extent polymorphonuclear neutrophils to adhere to platelets. Both platelet-leukocyte interaction and platelet aggregation in whole blood were inhibited by blockade of CD14 and TLR4. Moreover, the interaction between platelets and leukocytes was inhibited by P-selectin, and by blockade of PAF and reactive oxygen species, suggesting a role of P-selectin and of leukocyte-derived mediators. In conclusion, these results elucidate the mechanisms leading to platelet activation and interaction with leukocytes triggered by LPS. They suggest that the activation of platelets by LPS is mainly dependent on leukocytes and especially monocytes as a result of CD14 and TLR4 engagement. Moreover, we found that leukocyte-platelet interaction was triggered by the synthesis of PAF and the generation of oxygen radicals that induced upregulation of surface expression of P-selectin.

  15. Manipulation of Neutrophils by Porphyromonas gingivalis in the Development of Periodontitis.

    Science.gov (United States)

    Sochalska, Maja; Potempa, Jan

    2017-01-01

    The pathogenesis of the chronic periodontal disease is associated with a skewed host inflammatory response to periodontal pathogens, such as Porphyromonas gingivalis , that accounts for the majority of periodontal tissue damage. Neutrophils are the most abundant leukocytes in periodontal pockets and depending on the stage of the disease, also plentiful PMNs are present in the inflamed gingival tissue and the gingival crevice. They are the most efficient phagocytes and eliminate pathogens by a variety of means, which are either oxygen-dependent or -independent. However, these secretory lethal weapons do not strictly discriminate between pathogens and host tissue. Current studies describe conflicting findings about neutrophil involvement in periodontal disease. On one hand literature indicate that hyper-reactive neutrophils are the main immune cell type responsible for this observed tissue damage and disease progression. Deregulation of neutrophil survival and functions, such as chemotaxis, migration, secretion of antimicrobial peptides or enzymes, and production of reactive oxygen species, contribute to observed tissue injury and the clinical signs of periodontal disease. On the other hand neutrophils deficiencies in patients and mice also result in periodontal phenotype. Therefore, P. gingivalis represents a periodontal pathogen that manipulates the immune responses of PMNs, employing several virulence factors, such as gingipains, serine proteases, lipid phosphatases, or fimbriae. This review will sum up studies devoted to understanding different strategies utilized by P. gingivalis to manipulate PMNs survival and functions in order to inhibit killing by a granular content, prolong inflammation, and gain access to nutrient resources.

  16. Manipulation of Neutrophils by Porphyromonas gingivalis in the Development of Periodontitis

    Directory of Open Access Journals (Sweden)

    Maja Sochalska

    2017-05-01

    Full Text Available The pathogenesis of the chronic periodontal disease is associated with a skewed host inflammatory response to periodontal pathogens, such as Porphyromonas gingivalis, that accounts for the majority of periodontal tissue damage. Neutrophils are the most abundant leukocytes in periodontal pockets and depending on the stage of the disease, also plentiful PMNs are present in the inflamed gingival tissue and the gingival crevice. They are the most efficient phagocytes and eliminate pathogens by a variety of means, which are either oxygen-dependent or -independent. However, these secretory lethal weapons do not strictly discriminate between pathogens and host tissue. Current studies describe conflicting findings about neutrophil involvement in periodontal disease. On one hand literature indicate that hyper-reactive neutrophils are the main immune cell type responsible for this observed tissue damage and disease progression. Deregulation of neutrophil survival and functions, such as chemotaxis, migration, secretion of antimicrobial peptides or enzymes, and production of reactive oxygen species, contribute to observed tissue injury and the clinical signs of periodontal disease. On the other hand neutrophils deficiencies in patients and mice also result in periodontal phenotype. Therefore, P. gingivalis represents a periodontal pathogen that manipulates the immune responses of PMNs, employing several virulence factors, such as gingipains, serine proteases, lipid phosphatases, or fimbriae. This review will sum up studies devoted to understanding different strategies utilized by P. gingivalis to manipulate PMNs survival and functions in order to inhibit killing by a granular content, prolong inflammation, and gain access to nutrient resources.

  17. The selective estrogen receptor modulator raloxifene inhibits neutrophil extracellular trap formation.

    Directory of Open Access Journals (Sweden)

    Roxana Flores

    2016-12-01

    Full Text Available Raloxifene is a selective estrogen receptor modulator typically prescribed for the prevention/treatment of osteoporosis in postmenopausal women. Although raloxifene is known to have anti-inflammatory properties, its effect on human neutrophils, the primary phagocytic leukocytes of the immune system, remain poorly understood. Here, through a screen of pharmacologically active small molecules, we find that raloxifene prevents neutrophil cell death in response to the classical activator phorbol 12-myristate 13-acetate (PMA, a compound known to induce formation of DNA-based neutrophil extracellular traps (NETs. Inhibition of PMA-induced NET production by raloxifene was confirmed using quantitative and imaging-based assays. Human neutrophils from both male and female donors express the nuclear estrogen receptors ERα and ERβ, known targets of raloxifene. Like raloxifene, selective antagonists of these receptors inhibit PMA-induced NET production. Furthermore, raloxifene inhibited PMA-induced ERK phosphorylation but not reactive oxygen species (ROS production, pathways known to be key modulators of NET production. Finally, we found that raloxifene inhibited PMA-induced, NET-based killing of the leading human bacterial pathogen, methicillin-resistant Staphylococcus aureus (MRSA. Our results reveal that raloxifene is a potent modulator of neutrophil function and NET production.

  18. Candida albicans Biofilms Do Not Trigger Reactive Oxygen Species and Evade Neutrophil Killing

    Science.gov (United States)

    Xie, Zhihong; Thompson, Angela; Sobue, Takanori; Kashleva, Helena; Xu, Hongbin; Vasilakos, John; Dongari-Bagtzoglou, Anna

    2012-01-01

    Neutrophils are found within Candida albicans biofilms in vivo and could play a crucial role in clearing the pathogen from biofilms forming on catheters and mucosal surfaces. Our goal was to compare the antimicrobial activity of neutrophils against developing and mature C. albicans biofilms and identify biofilm-specific properties mediating resistance to immune cells. Antibiofilm activity was measured with the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)2H-tetrazolium-5-carboxanilide assay and a molecular Candida viability assay. Reactive oxygen species generation was assessed by measuring fluorescence of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester in preloaded neutrophils. We found that mature biofilms were resistant to leukocytic killing and did not trigger reactive oxygen species, even though neutrophils retained their viability and functional activation potential. Beta-glucans found in the extracellular matrix negatively affected antibiofilm activities. We conclude that these polymers act as a decoy mechanism to prevent neutrophil activation and that this represents an important innate immune evasion mechanism of C. albicans biofilms. PMID:23033146

  19. Complete identification of E-selectin ligand activity on neutrophils reveals a dynamic interplay and distinct functions of PSGL-1, ESL-1 and CD44

    Science.gov (United States)

    Wild, Martin; Vestweber, Dietmar; Frenette, Paul S.

    2014-01-01

    SUMMARY The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro but the complete identification of its physiological ligands has remained elusive. Here, we show using gene- and RNA-targeted loss-of-function that E-selectin ligand-1 (ESL-1), PSGL-1 and CD44 encompass all endothelial selectin ligand activity on neutrophils. PSGL-1 plays a major role in the initial leukocyte capture, while ESL-1 is critical to convert initial tethers into steady slow rolling. CD44 controls rolling velocity and mediates E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling. PMID:17442598

  20. Single-cell Raman and fluorescence microscopy reveal the association of lipid bodies with phagosomes in leukocytes

    Science.gov (United States)

    van Manen, Henk-Jan; Kraan, Yvonne M.; Roos, Dirk; Otto, Cees

    2005-01-01

    Cellular imaging techniques based on vibrational spectroscopy have become powerful tools in cell biology because the molecular composition of subcellular compartments can be visualized without the need for labeling. Using high-resolution, nonresonant confocal Raman microscopy on individual cells, we demonstrate here that lipid bodies (LBs) rich in arachidonate as revealed by their Raman spectra associate with latex bead-containing phagosomes in neutrophilic granulocytes. This finding was corroborated in macrophages and in PLB-985 cells, which can be induced to differentiate into neutrophil-like cells, by selective staining of LBs and visualization by confocal fluorescence microscopy. We further show that the accumulation of LBs near phagosomes is mediated at least in part by the flavohemoprotein gp91phox (in which “phox” is phagocyte oxidase), because different LB distributions around phagocytosed latex beads were observed in WT and gp91phox-deficient PLB-985 cells. gp91phox, which accumulates in the phagosomal membrane, is the catalytic subunit of the leukocyte NADPH oxidase, a critical enzyme in the innate immune response. Finally, time-lapse fluorescence microscopy experiments on neutrophils revealed that the LB-phagosome association is transient, similar to the “kiss-and-run” behavior displayed by endosomes involved in phagosome maturation. Because arachidonic acid (AA) has been shown to be involved in NADPH oxidase activation and phagosome maturation in neutrophils and macrophages, respectively, the findings reported here suggest that LBs may provide a reservoir of AA for local activation of these essential leukocyte functions. PMID:16002471

  1. Scintigraphy with In-111 labeled leukocytes

    International Nuclear Information System (INIS)

    Itoh, Kazuo; Tsukamoto, Eriko; Furudate, Masayori; Saito, Chihoko.

    1987-01-01

    With increasing necessity for In-111 labeled leukocyte scintigraphy (ILLS) as a routine examination, a problem of complicated labeling of leukocytes has arisen. In this study, simplified labeling of leukocytes was examined with respect to its ability to detect abscesses. Simplified labeling method yielded significantly satisfactory results for recovery and labeling rates of leukocytes, as compared with conventional recommended method. Therefore, ILLS by simplified technique was clinically applied in 58 patients with suppurative or non-suppurative diseases who gave informed consent. In an analysis of ILLS for detecting suppurative region, the sensitivity, specificity, and corrected specificity were found to be 81 %, 75 %, and 82 %, respectively. (Namekawa, K.)

  2. [Mechanisms of leukocyte formation of endogenous pyrogen].

    Science.gov (United States)

    Rybakina, E G; Sorokin, A V

    1982-06-01

    A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

  3. Evaluation of four methods for separation of lymphocytes from normal individuals and patients with cancer and tuberculosis.

    Science.gov (United States)

    Patrick, C C; Graber, C D; Loadholt, C B

    1976-01-01

    An optimal technique was sought for lymphocyte recovery from normal and chronic diseased individuals. Lymphocytes were separated by four techniques: Plasmagel, Ficoll--Hypaque, a commercial semiautomatic method, and simple centrifugation using blood drawn from ten normal individuals, ten cancer patients, and ten tuberculosis patients. The lymphocyte mixture obtained after using each method was analyzed for percent recovery, amount if contamination by erythrocytes and neutrophils, and percent viability. The results show that the semiautomatic method yielded the best percent recovery of lymphocytes for normal individuals, while the simple centrifugation method contributed the highest percent recovery for cancer and tuberculosis patients. The Ficoll-Hypaque method gave the lowest erythrocyte contamination for all three types of individuals tested, while the Plasmagel method gave the lowest neutrophil contamination for all three types of individuals. The simple centrifugation method yielded all viable lymphocytes and thus gave the highest percent viability.

  4. Radiation effects on lymphocytes

    International Nuclear Information System (INIS)

    Roser, B.

    1976-01-01

    This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

  5. GMP-140 binds to a glycoprotein receptor on human neutrophils: Evidence for a lectin-like interaction

    International Nuclear Information System (INIS)

    Moore, K.L.; Varki, A.; McEver, R.P.

    1991-01-01

    GMP-140 is a rapidly inducible receptor for neutrophils and monocytes expressed on activated platelets and endothelial cells. It is a member of the selectin family of lectin-like cell surface molecules that mediate leukocyte adhesion. We used a radioligand binding assay to characterize the interaction of purified GMP-140 with human neutrophils. Unstimulated neutrophils rapidly bound [125I]GMP-140 at 4 degrees C, reaching equilibrium in 10-15 min. Binding was Ca2+ dependent, reversible, and saturable at 3-6 nM free GMP-140 with half-maximal binding at approximately 1.5 nM. Receptor density and apparent affinity were not altered when neutrophils were stimulated with 4 beta-phorbol 12-myristate 13-acetate. Treatment of neutrophils with proteases abolished specific binding of [125I]GMP-140. Binding was also diminished when neutrophils were treated with neuraminidase from Vibrio cholerae, which cleaves alpha 2-3-, alpha 2-6-, and alpha 2-8-linked sialic acids, or from Newcastle disease virus, which cleaves only alpha 2-3- and alpha 2-8-linked sialic acids. Binding was not inhibited by an mAb to the abundant myeloid oligosaccharide, Lex (CD15), or by the neoglycoproteins Lex-BSA and sialyl-Lex-BSA. We conclude that neutrophils constitutively express a glycoprotein receptor for GMP-140, which contains sialic acid residues that are essential for function. These findings support the concept that GMP-140 interacts with leukocytes by a lectin-like mechanism

  6. Worm burden and leukocyte response in Angiostrongylus malaysiensis-infected rats: the influence of testosterone.

    Science.gov (United States)

    Kamis, A B; Ahmad, R A; Badrul-Munir, M Z

    1992-01-01

    Gonadectomized male albino rats aged 7 weeks were given 1.5 mg/kg testosterone propionate daily and inoculated with 50 third-stage larvae of Angiostrongylus malaysiensis. The treatment significantly increased the number of larvae and adult worms recovered from the brain and pulmonary arteries, respectively, and the rats exhibited smaller thymus glands. The total numbers of leukocytes, monocytes, neutrophils, and especially eosinophils increased significantly post-infection, but the counts were higher in the untreated infected controls. Presumably, immunosuppressive effects of testosterone may at least partly be responsible for the higher loads of A. malaysiensis worms found in male rats as compared with females in the field.

  7. Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

    Science.gov (United States)

    Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

    2009-06-10

    Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane.

  8. Immune modulation by neutrophil subsets

    NARCIS (Netherlands)

    Kamp, V.M.

    2013-01-01

    We show that human neutrophils can suppress T-cell proliferation in acute systemic inflammation and thus have anti-inflammatory functions, next to their well-known pro-inflammatory functions. The suppression is mediated by ROS production and integrin MAC-1, which are also important for the

  9. An intense and short-lasting burst of neutrophil activation differentiates early acute myocardial infarction from systemic inflammatory syndromes.

    Directory of Open Access Journals (Sweden)

    Norma Maugeri

    Full Text Available BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS, 69 with chronic stable angina (CSA, 50 with inflammation due to either non-infectious (acute bone fracture, infectious (sepsis or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis. Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization. One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via

  10. Modulation and Apoptosis of Neutrophil Granulocytes by Extracorporeal Photopheresis in the Treatment of Chronic Graft-Versus-Host Disease.

    Directory of Open Access Journals (Sweden)

    Cindy Franklin

    Full Text Available Chronic graft-versus-host disease (cGVHD is a common side effect of allogeneic stem cell transplantation and a major cause of morbidity and mortality in affected patients. Especially skin, eyes and oral mucosa are affected. This can lead to pain and functional impairment. Extracorporeal photopheresis (ECP is an effective immunomodulatory therapy with minimal side effects but its mode of action is still largely unknown. The objective of the present study was to examine the effects of ECP on neutrophil granulocytes in patients with cGVHD. Analysis of leukocytes from cGVHD patients obtained from the ECP device during treatment showed that neutrophil granulocytes account for the majority of cells treated during ECP. Neutrophils from healthy donors treated in vitro with 8-methoxypsoralen and UVA light as well as neutrophils from buffy coats of patients with cGVHD treated by ECP showed increased apoptosis and decreased half-life. In remaining non-apoptotic cells chemoirradiation resulted in loss of activation markers and reduced effector functions. This was accompanied by an increase in extracellular arginase-1 activity. Additional comparison of neutrophils isolated from blood of cGVHD patients before and 24h after ECP revealed a decreased half-life and reduction of effector functions of post-ECP neutrophils ex vivo. These observations strongly suggest that ECP induces both apoptosis and physiological changes in neutrophils and that these changes also take place in vivo. This study is the first to show that ECP modulates apoptosis and inflammatory activity in neutrophil granulocytes, indicating that neutrophils may significantly contribute to the overall immunomodulatory effects attributed to this treatment.

  11. Degree of neutrophil, atrophy, and metaplasia intestinal were associate with malondialdehyde level in gastritis patients

    Science.gov (United States)

    Siregar, G. A.; Sari, D. K.; Sungkar, T.

    2018-03-01

    The main pathogenesis of gastritis is inflammation that closely related to free radicals. Malondialdehyde (MDA) is a free radical biomarker and is found to increase in gastritis patients. However, these studies are generally performed on experimental animals as well as MDA examination in gastric mucosa. This study aim was to determine the association of degrees of gastritis (degree of lymphocyte infiltration, neutrophil activity, atrophy, and intestinal metaplasia) with plasma MDA level. A cross-sectional study of 80 consecutive gastritis patients who came to an endoscopic unit of Adam Malik General Hospital in Medan, Indonesia, from May–September 2017. Assessed for severity of chronic inflammatory, neutrophil activity, atrophy, and intestinal metaplasia refers to Updated Sydney System. Plasma MDA levels were examined using an HPLC MDA kit. Univariate analysis, bivariate (chi-square and Fisher exact test), and multivariate (binary logistic regression test) were programmed with SPSS version 22. There was no significant association between degree of lymphocyte infiltration with MDA level. There were significant associations between degree of neutrophil activity, atrophy, and intestinal metaplasia with MDA level (p=0.039, 0.003, 0.021; respectively). The moderate+severe degree of neutrophil activity, atrophy, and intestinal metaplasia were associated with high level of MDA.

  12. Flow cytofluorometric assay of human whole blood leukocyte DNA degradation in response to Yersinia pestis and Staphylococcus aureus

    Science.gov (United States)

    Kravtsov, Alexander L.; Grebenyukova, Tatyana P.; Bobyleva, Elena V.; Golovko, Elena M.; Malyukova, Tatyana A.; Lyapin, Mikhail N.; Kostyukova, Tatyana A.; Yezhov, Igor N.; Kuznetsov, Oleg S.

    2001-05-01

    Human leukocytes containing less than 2C DNA per cell (damaged or dead cells) were detected and quantified by flow cytometry and DNA-specific staining with ethidium bromide and mithramycin in whole blood infected with Staphylococcus aureus or Yersinia pestis. Addition of live S. aureus to the blood (100 microbe cells per one leukocyte) resulted in rapid degradation of leukocyte DNA within 3 to 6 hours of incubation at 37 degree(s)C. However, only about 50 percent cells were damaged and the leukocytes with the intact genetic apparatus could be found in the blood for a period up to 24 hours. The leukocyte injury was preceded by an increase of DNA per cell content (as compared to the normal one) that was likely to be connected with the active phagocytosis of S. aureus by granulocytes (2C DNA of diploid phagocytes plus the all bacterial DNA absorbed). In response to the same dose of actively growing (at 37 degree(s)C) virulent Y. pestis cells, no increase in DNA content per cell could be observed in the human blood leukocytes. The process of the leukocyte DNA degradation started after a 6-hour incubation, and between 18 to 24 hours of incubation about 90 percent leukocytes (phagocytes and lymphocytes) lost their specific DNA fluorescence. These results demonstrated a high potential of flow cytometry in comparative analysis in vitro of the leukocyte DNA degradation process in human blood in response to bacteria with various pathogenic properties. They agree with the modern idea of an apoptotic mechanism of immunosuppression in plague.

  13. Leukocyte telomere dynamics in the elderly

    DEFF Research Database (Denmark)

    Steenstrup, Troels; Hjelmborg, Jacob V B; Mortensen, Laust H

    2013-01-01

    Limited data suggest that leukocytes of the elderly display ultra-short telomeres. It was reported that in some elderly persons leukocyte telomere length (LTL) shows age-dependent elongation. Using cross-sectional and longitudinal models, we characterized LTL dynamics in participants...

  14. Staphylococcus epidermidis strategies to avoid killing by human neutrophils.

    Directory of Open Access Journals (Sweden)

    Gordon Y C Cheung

    2010-10-01

    Full Text Available Staphylococcus epidermidis is a leading nosocomial pathogen. In contrast to its more aggressive relative S. aureus, it causes chronic rather than acute infections. In highly virulent S. aureus, phenol-soluble modulins (PSMs contribute significantly to immune evasion and aggressive virulence by their strong ability to lyse human neutrophils. Members of the PSM family are also produced by S. epidermidis, but their role in immune evasion is not known. Notably, strong cytolytic capacity of S. epidermidis PSMs would be at odds with the notion that S. epidermidis is a less aggressive pathogen than S. aureus, prompting us to examine the biological activities of S. epidermidis PSMs. Surprisingly, we found that S. epidermidis has the capacity to produce PSMδ, a potent leukocyte toxin, representing the first potent cytolysin to be identified in that pathogen. However, production of strongly cytolytic PSMs was low in S. epidermidis, explaining its low cytolytic potency. Interestingly, the different approaches of S. epidermidis and S. aureus to causing human disease are thus reflected by the adaptation of biological activities within one family of virulence determinants, the PSMs. Nevertheless, S. epidermidis has the capacity to evade neutrophil killing, a phenomenon we found is partly mediated by resistance mechanisms to antimicrobial peptides (AMPs, including the protease SepA, which degrades AMPs, and the AMP sensor/resistance regulator, Aps (GraRS. These findings establish a significant function of SepA and Aps in S. epidermidis immune evasion and explain in part why S. epidermidis may evade elimination by innate host defense despite the lack of cytolytic toxin expression. Our study shows that the strategy of S. epidermidis to evade elimination by human neutrophils is characterized by a passive defense approach and provides molecular evidence to support the notion that S. epidermidis is a less aggressive pathogen than S. aureus.

  15. Biodistribution of radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1985-01-01

    Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

  16. Whole blood microculture assay of human lymphocyte function.

    Science.gov (United States)

    Pauly, J L; Han, T

    1976-11-01

    A whole blood microculture assay is described for measuring lymphocyte reactivity to mitogenic and antigenic stimulants. This assay employs heparinized whole blood, serum-free culture medium, microtiter plates, and a Multiple Automated Sample Harvester (MASH). When this assay is compared to other leukocyte assays, its major advantages include (1) the utilization of fewer lymphocytes per microculture, thuus reducing the amount of blood required per test while increasing the number of test agents and replicate cultures which can be employed in any given experiment; (2) the conservation of mitogens, antigens, drugs, enzymes, hormones, lymphokines, and other test agents, some of which are either expensive of difficult to prepare in large quantities; (3) the elimination of lymphocyte isolation and purification procedures which may disrupt the relative proportion of T cells, B cells and antigen-processing cells; and (4) the application of an automated harvester which simplifies and expedites procedures required for processing cells for liquid scintillation counting.

  17. A Novel Centrifugation Method Using a Cell Salvage Device Offers an Alternative to the Use of Leukocyte-Depleting Filters for Autologous Blood Transfusions.

    Science.gov (United States)

    Barchilon, Michael; Gaspar, Cristina; Mexas, Angela; Nieter, Don

    2016-12-01

    Autotransfusion protocols often use the use of costly filters, such as leukocyte-depleting filters (LDFs), to minimize reinfusion of activated leukocytes and inflammatory mediators associated with reperfusion injury (RI). LDFs are used extensively in hospital settings; however, they represent an additional capital expenditure for hospitals, as well as a constraint on the reinfusion rate of blood products for health-care providers. We compared a commonly used LDF to a novel centrifugation method employing a widely used cell salvage device. Complete blood counts and enzyme-linked immunosorbent assays (ELISAs) measuring tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were performed to compare the efficacy of these methodologies. The LDF removed, on average, 94% of all leukocytes, including 96% of neutrophils. The centrifugation method removed, on average, 89% of all leukocytes, including 91% of neutrophils and resulted in a highly concentrated red blood cell product. Our results suggest both methods offer equivalent leukocyte reduction. TNF-α was also comparably reduced following our novel centrifugation method and the LDF method and IL-2 levels were undetectable in all samples. These results indicate our novel centrifugation method may preclude the need for a LDF during select autotransfusion applications.

  18. The tripeptide feG regulates the production of intracellular reactive oxygen species by neutrophils

    Directory of Open Access Journals (Sweden)

    Davison Joseph S

    2006-06-01

    Full Text Available Abstract Background The D-isomeric form of the tripeptide FEG (feG is a potent anti-inflammatory agent that suppresses type I hypersensitivity (IgE-mediated allergic reactions in several animal species. One of feG's primary actions is to inhibit leukocyte activation resulting in loss of their adhesive and migratory properties. Since activation of neutrophils is often associated with an increase in respiratory burst with the generation of reactive oxygen species (ROS, we examined the effect of feG on the respiratory burst in neutrophils of antigen-sensitized rats. A role for protein kinase C (PKC in the actions of feG was evaluated by using selective isoform inhibitors for PKC. Results At 18h after antigen (ovalbumin challenge of sensitized Sprague-Dawley rats a pronounced neutrophilia occurred; a response that was reduced in animals treated with feG (100 μg/kg. With antigen-challenged animals the protein kinase C (PKC activator, PMA, significantly increased intracellular ROS of circulating neutrophils, as determined by flow cytometry using the fluorescent probe dihydrorhodamine-123. This increase was prevented by treatment with feG at the time of antigen challenge. The inhibitor of PKCδ, rottlerin, which effectively prevented intracellular ROS production by circulating neutrophils of animals receiving a naïve antigen, failed to inhibit PMA-stimulated ROS production if the animals were challenged with antigen. feG treatment, however, re-established the inhibitory effects of the PKCδ inhibitor on intracellular ROS production. The extracellular release of superoxide anion, evaluated by measuring the oxidative reduction of cytochrome C, was neither modified by antigen challenge nor feG treatment. However, hispidin, an inhibitor of PKCβ, inhibited the release of superoxide anion from circulating leukocytes in all groups of animals. feG prevented the increased expression of the β1-integrin CD49d on the circulating neutrophils elicited by antigen

  19. Monoclonal antibodies and coupling reagents to cell membrane proteins for leukocyte labeling

    International Nuclear Information System (INIS)

    McAfee, J.G.; Gagne, G.; Subramanian, G.; Schneider, R.F.

    1984-01-01

    Current gamma-emitting agents for tagging leukocytes, In-111 oxine or tropolone, label all cell types indiscriminantly, and nuclear localization in lymphocytes results in radiation damage. Coupling reagents and murine monoclonal antibodies (Mab) specific for cell surface antigens of human leukocytes were tried as cell labeling agents to avoid nuclear localization. 10/sup 8/ mixed human leukocytes in Hepes buffer were added to tubes coated with 5 mg of dry cyclic dianhydride of DTPA for 15 minutes at room temperature. After washing, 0.1 ml of In-111 Cl in ACD (pH 6.8) was added. After 30 minutes, a cell labeling yield of 23% was obtained. Washing the cells in an elutriation centrifuge showed that this label was irreversible. Mab for cell surface antigens of human granulocytes were labeled with 300 μCi of I-125 using the Iodobead technic and unbound activity was removed by gel column chromatography. 1-10 μg were added to 10/sup 8/ mixed leukocytes in 0.5 ml plasma or saline for 1 hr. With Mab anti-leu M4 (clone G7 E11), an IgM, the cell labeling yield was 21%, irreversible, and specific for granulocytes. With anti-human leukocyte Mab NEI-042 (clone 9.4), and IgG2a, and anti-granulocyte Mab MAS-065 (clone FMCl1) an IgG1, the cell labeling was relatively unstable. Labeling of leukocyte subpopulations with Mab is feasible, and the binding of multivalent IgM is stronger than that of other immunoglobulins. DTPA cyclic anhydride is firmly bound to cell membranes, but the labeling is non-specific

  20. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Ignacio eMelero

    2013-12-01

    Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

  1. CD44 antibody stimulates adhesion of peripheral blood T cells to keratinocytes through the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway

    NARCIS (Netherlands)

    Bruynzeel, I.; Koopman, G.; van der Raaij, L. M.; Pals, S. T.; Willemze, R.

    1993-01-01

    Close contact between T lymphocytes and keratinocytes is an important feature of many inflammatory skin diseases. In vitro studies showed that stimulation of keratinocytes with interferon-gamma or tumor necrosis factor-alpha and of T cells with phorbol esters results in a leukocyte

  2. Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs

    Science.gov (United States)

    Lindemann, Stephan W.; Yost, Christian C.; Denis, Melvin M.; McIntyre, Thomas M.; Weyrich, Andrew S.; Zimmerman, Guy A.

    2004-05-01

    The mechanisms by which neutrophils, key effector cells of the innate immune system, express new gene products in inflammation are largely uncharacterized. We found that they rapidly translate constitutive mRNAs when activated, a previously unrecognized response. One of the proteins synthesized without a requirement for transcription is the soluble IL-6 receptor , which translocates to endothelial cells and induces a temporal switch to mononuclear leukocyte recruitment. Its synthesis is regulated by a specialized translational control pathway that is inhibited by rapamycin, a bacterial macrolide with therapeutic efficacy in transplantation, inflammatory syndromes, and neoplasia. Signal-dependent translation in activated neutrophils may be a critical mechanism for alteration of the inflammatory milieu and a therapeutic target.

  3. Down-regulated resistin level in consequence of decreased neutrophil counts in untreated Grave's disease.

    Science.gov (United States)

    Peng, Ying; Qi, Yicheng; Huang, Fengjiao; Chen, Xinxin; Zhou, Yulin; Ye, Lei; Wang, Weiqing; Ning, Guang; Wang, Shu

    2016-11-29

    Resistin, belongs to cysteine-rich secretory protein, is mainly produced by circulating leukocytes, such as neutrophils monocytes and macrophages in humans. To date, few but controversial studies have reported about resistin concentrations in hyperthyroid patients, especially in Graves' disease (GD). We undertaked a controlled, prospective study to explore the serum resistin concentration in GD patients before and after -MMI treatment. In addition, we also investigated the main influencing factor on serum resistin level and discuessed the potential role of serum resistin plays in GD patients. 39 untreated GD (uGD) patients, including 8 males and 31 females, were enrolled in our investigation. All of these patients were prescribed with MMI treatment, in addition to 25 healthy controls. Anthropometric parameters and hormone assessment were measured. Enzyme-linked immunosorbent assay was used to detect serum resistin concentration in different stages of GD patients. Furthermore, neutrophil cell line NB4 with or without T3 treatment to detect the effect of thyroid hormones on resistin expression. The serum resistin level and neutrophil counts in untreated GD patients were significantly declined. And all of these parameters were recovered to normal after MMI treatment in ethyroid GD (eGD) and TRAb-negative conversion (nGD) patients. Resistin concentration exhibited a negative correlation with FT3 and FT4, but a positive correlation with absolute number of neutrophiles in uGD patients, whereas did not correlate with thyroid autoimmune antibodies and BMI. Neutrophile cell line, NB4, produced decreased expression of resistin when stimulated with T3. Our study showed a decrease of serum resistin level in GD patients and we suggested that the serum resistin might primarily secreted from circulating neutrophils and down-regulated by excessive thyroid hormones in GD patients.

  4. Biomaterial associated impairment of local neutrophil function.

    Science.gov (United States)

    Kaplan, S S; Basford, R E; Kormos, R L; Hardesty, R L; Simmons, R L; Mora, E M; Cardona, M; Griffith, B L

    1990-01-01

    The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

  5. Effect of sevoflurane on human neutrophil apoptosis.

    LENUS (Irish Health Repository)

    Tyther, R

    2012-02-03

    BACKGROUND AND OBJECTIVE: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo. METHODS: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1. RESULTS: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane. CONCLUSIONS: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

  6. Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

    Science.gov (United States)

    Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

    2018-03-01

    Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

  7. Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity

    Directory of Open Access Journals (Sweden)

    Jiehao Zhou

    2010-01-01

    Full Text Available We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE. The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP- 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P<.05. Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P<.05 and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier.

  8. Leukocyte integrins and their ligand interactions

    Science.gov (United States)

    Hyun, Young-Min; Lefort, Craig T.; Kim, Minsoo

    2010-01-01

    Although critical for cell adhesion and migration during normal immune-mediated reactions, leukocyte integrins are also involved in the pathogenesis of diverse clinical conditions including autoimmune diseases and chronic inflammation. Leukocyte integrins therefore have been targets for anti-adhesive therapies to treat the inflammatory disorders. Recently, the therapeutic potential of integrin antagonists has been demonstrated in psoriasis and multiple sclerosis. However, current therapeutics broadly affect integrin functions and, thus, yield unfavorable side effects. This review discusses the major leukocyte integrins and the anti-adhesion strategies for treating immune diseases. PMID:19184539

  9. NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma

    Science.gov (United States)

    Wilson, C. L.; Jurk, D.; Fullard, N.; Banks, P.; Page, A.; Luli, S.; Elsharkawy, A. M.; Gieling, R. G.; Chakraborty, J. Bagchi; Fox, C.; Richardson, C.; Callaghan, K.; Blair, G. E.; Fox, N.; Lagnado, A.; Passos, J. F.; Moore, A. J.; Smith, G. R.; Tiniakos, D. G.; Mann, J.; Oakley, F.; Mann, D. A.

    2015-04-01

    Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1S340A/S340Amice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC.

  10. Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

    Science.gov (United States)

    Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar

    2011-08-01

    Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

  11. [Effects of HiLo for two weeks on erythrocyte immune adhesion and leukocyte count of swimmers].

    Science.gov (United States)

    Zhao, Yong-Cai; Gao, Bing-Hong; Wu, Ge-Lin; Zhang, Jiu-Li

    2012-07-01

    To investigate the effects of living high-training low (HiLo) on innate immunity in blood of elite swimmers. Six female swimmers undertook HiLo for two weeks, erythrocyte adhesion function and counts of leukocyte were tested in different time of training period. Red blood cell C3b receptor ring rate (RBC-C3bRR) decreased and red blood cell immune complex matter ring rate (RBC-ICR) increased significantly (P < 0.05), the two markers returned to base line 1 week after training. Counts of leukocyte and granulocyte decreased significantly (P < 0.05), and they recovered 1 week after training; Counts of lymphocyte and monocyte decreased without significance during training and did not recovered after training. Immunity of erythrocyte and granulocyte decreased quickly, but lymphocyte and monocyte recovered slowly, swimmers were adaptive to the training.

  12. Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients

    International Nuclear Information System (INIS)

    Gridley, D.S.; Slater, J.M.; Stickney, D.R.

    1990-01-01

    This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients

  13. Effect of Intensity of Cigarette Smoking on Leukocytes among Adult Men and Women Smokers in Bangladesh

    Directory of Open Access Journals (Sweden)

    Shahena Shipa

    2017-03-01

    Full Text Available Background: Smoking is one of the preventable causes of disease in middle and low-income countries. This study was conducted in smokers and non-smokers to observe the changes in total count of leukocytes in cigarette smokers in relation to body mass index (BMI and blood pressure (BP. Methods:The study populations were from different sources including diagnostic center and general hospital, and consisted of 58 smokers and 77 non-smokers, with a broad range of age groups. The variables considered for this study were the smoking status of current smokers and non-smokers, and blood samples of the subject, anthropometric data and also blood pressure data. Results: Total leukocytes in smokers were found to be higher than the non-smokers along with the increasing of lymphocytes. Leukocytes were also found to be increased with intensity of smoking in adult men and women. The BMI of the smokers showed decreasing trend compared to non-smokers. The relation between blood pressure and smoking was not well established, as there were only little changes on systolic blood pressure (SBP of smokers found according to smoking intensity. Conclusion: Cigarette smoking has negative effects on leukocytes both in men and women smokers in terms of certain anthropometric parameters.

  14. Maternal T-Cell Engraftment Interferes With Human Leukocyte Antigen Typing in Severe Combined Immunodeficiency.

    Science.gov (United States)

    Liu, Chang; Duffy, Brian; Bednarski, Jeffrey J; Calhoun, Cecelia; Lay, Lindsay; Rundblad, Barrett; Payton, Jacqueline E; Mohanakumar, Thalachallour

    2016-02-01

    To report the laboratory investigation of a case of severe combined immunodeficiency (SCID) with maternal T-cell engraftment, focusing on the interference of human leukocyte antigen (HLA) typing by blood chimerism. HLA typing was performed with three different methods, including sequence-specific primer (SSP), sequence-specific oligonucleotide, and Sanger sequencing on peripheral blood leukocytes and buccal cells, from a 3-month-old boy and peripheral blood leukocytes from his parents. Short tandem repeat (STR) testing was performed in parallel. HLA typing of the patient's peripheral blood leukocytes using the SSP method demonstrated three different alleles for each of the HLA-B and HLA-C loci, with both maternal alleles present at each locus. Typing results from the patient's buccal cells showed a normal pattern of inheritance for paternal and maternal haplotypes. STR enrichment testing of the patient's CD3+ T lymphocytes and CD15+ myeloid cells confirmed maternal T-cell engraftment, while the myeloid cell profile matched the patient's buccal cells. Maternal T-cell engraftment may interfere with HLA typing in patients with SCID. Selection of the appropriate typing methods and specimens is critical for accurate HLA typing and immunologic assessment before allogeneic hematopoietic stem cell transplantation. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

    Science.gov (United States)

    Marino, Jose; Babiker-Mohamed, Mohamed H.; Crosby-Bertorini, Patrick; Paster, Joshua T.; LeGuern, Christian; Germana, Sharon; Abdi, Reza; Uehara, Mayuko; Kim, James I.; Markmann, James F.; Tocco, Georges; Benichou, Gilles

    2016-01-01

    Transplantation of allogeneic organs and tissues represents a lifesaving procedure for a variety of patients affected with end-stage diseases. Although current immunosuppressive therapy prevents early acute rejection, it is associated with nephrotoxicity and increased risks for infection and neoplasia. This stresses the need for selective immune-based therapies relying on manipulation of lymphocyte recognition of donor antigens. The passenger leukocyte theory states that allograft rejection is initiated by recipient T cells recognizing donor major histocompatibility complex (MHC) molecules displayed on graft leukocytes migrating to the host’s lymphoid organs. We revisited this concept in mice transplanted with allogeneic skin, heart, or islet grafts using imaging flow cytometry. We observed no donor cells in the lymph nodes and spleen of skin-grafted mice, but we found high numbers of recipient cells displaying allogeneic MHC molecules (cross-dressed) acquired from donor microvesicles (exosomes). After heart or islet transplantation, we observed few donor leukocytes (100 per million) but large numbers of recipient cells cross-dressed with donor MHC (>90,000 per million). Last, we showed that purified allogeneic exosomes induced proinflammatory alloimmune responses by T cells in vitro and in vivo. Collectively, these results suggest that recipient antigen-presenting cells cross-dressed with donor MHC rather than passenger leukocytes trigger T cell responses after allotransplantation. PMID:27942611

  16. Use of 51Cr release to measure the cytotoxic effects of staphylococcal leukocidin and toxin neutralization on bovine leukocytes

    International Nuclear Information System (INIS)

    Loeffler, D.A.; Schat, K.A.; Norcross, N.L.

    1986-01-01

    Leukocidin toxin from Staphylococcus aureus produces specific cytolytic effects on neutrophils and macrophages. The most commonly used method for determination of leukocidin activity is microscopic examination for characteristic morphological changes in toxin-treated cells. The 51 Cr release assay was modified to allow quantitation of the cytolytic effects of leukocidin on bovine peripheral blood neutrophils and lymphocytes. Toxin neutralization by serum and milk samples was quantitated by this method. The neutralizing abilities of the various samples were found to correlate with the levels of immunoglobulin G (IgG1) specific for leukocidin. Undiluted normal serum samples, however, were capable of partially preventing the cytotoxic effects of leukocidin. The assay was shown to be an effective means of quantitating the cytotoxic activity of leukocidin on neutrophils as well as demonstrating neutralization of cytotoxicity by milk and serum samples

  17. Neutrophil Responses to Sterile Implant Materials.

    Directory of Open Access Journals (Sweden)

    Siddharth Jhunjhunwala

    Full Text Available In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices.

  18. Neutrophil Reverse Migration Becomes Transparent with Zebrafish

    Directory of Open Access Journals (Sweden)

    Taylor W. Starnes

    2012-01-01

    Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

  19. Neutrophils in Tuberculosis: Heterogeneity Shapes the Way?

    Science.gov (United States)

    2017-01-01

    Infection with M. tuberculosis remains one of the most common infections in the world. The outcome of the infection depends on host ability to mount effective protection and balance inflammatory responses. Neutrophils are innate immune cells implicated in both processes. Accordingly, during M. tuberculosis infection, they play a dual role. Particularly, they contribute to the generation of effector T cells, participate in the formation of granuloma, and are directly involved in tissue necrosis, destruction, and infection dissemination. Neutrophils have a high bactericidal potential. However, data on their ability to eliminate M. tuberculosis are controversial, and the results of neutrophil depletion experiments are not uniform. Thus, the overall roles of neutrophils during M. tuberculosis infection and factors that determine these roles are not fully understood. This review analyzes data on neutrophil defensive and pathological functions during tuberculosis and considers hypotheses explaining the dualism of neutrophils during M. tuberculosis infection and tuberculosis disease. PMID:28626346

  20. Neutrophil Extracellular Traps in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bjerg Bennike, Tue; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2015-01-01

    microscopy and confocal microscopy. RESULTS: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did...... not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were...... validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate...

  1. Synthesis of endogenous pyrogen by rabbit leukocytes.

    Science.gov (United States)

    Moore, D M; Murphy, P A; Chesney, P J; Wood, W B

    1973-05-01

    Rabbit ieukocytes from peritoneal exudates and from blood were stimulated to form leukocyte pyrogen in the presence of radiolabeled amino acids. The stimuli used were endotoxin, phagocytosis, and tuberculin. The crude leukocyte pyrogen samples were purified; pyrogen from exudate cells was rendered homogeneous; pyrogen from blood cells was still contaminated with other proteins. All the purified pyrogens were radioactive; and for all it was shown that radioactivity and pyrogenic activity coincided on electrophoresis at pH 3.5 and pH 9 in acrylamide and on isoelectric focusing in acrylamide. Furthermore, pyrogens obtained from exudate cells stimulated in different ways, or from blood cells and exudate cells stimulated with endotoxin, appeared to be identical. These results suggest that leukocyte pyrogen was synthesized de novo from amino acid precursors and that leukocytes made the same pyrogen whatever the stimulus used to activate them.

  2. Time course of leukocyte response and free radical release in an early reperfusion injury of the superior mesenteric artery

    Czech Academy of Sciences Publication Activity Database

    Hamar, J.; Rácz, I.; Číž, Milan; Lojek, Antonín; Pállinger, É.; Fűrész, J.

    2003-01-01

    Roč. 52, č. 4 (2003), s. 417-423 ISSN 0862-8408 R&D Projects: GA ČR GA524/00/1223 Grant - others:Hungarian National Research Fond(HU) OTKA 016314; Hungarian National Research Fond(HU) OTKA 29561 Institutional research plan: CEZ:AV0Z5004920 Keywords : rat * polymorphonuclear leukocytes * lymphocytes Subject RIV: BO - Biophysics Impact factor: 0.939, year: 2003

  3. Impaired neutrophil function in intestinal lymphangiectasia.

    OpenAIRE

    Bolton, R P; Cotter, K L; Losowsky, M S

    1986-01-01

    Impaired neutrophil chemotaxis and phagocytosis were shown in three patients with intestinal lymphangiectasia. Abnormalities in cell associated and serum derived activity occurred, and possible mechanisms are suggested.

  4. First report of changes in leukocyte morphology in response to inflammatory conditions in Asian and African elephants (Elephas maximus and Loxodonta africana.

    Directory of Open Access Journals (Sweden)

    Nicole I Stacy

    Full Text Available Although the hematology of healthy elephants has been well-described, published information on hematological changes during disease is limited. The objective of this study was to describe qualitative morphological changes in the leukocytes of Asian and African elephants (Elephas maximus and Loxodonta africana diagnosed with a variety of inflammatory conditions. Twenty-five of 27 elephants had morphological changes in their leukocytes, although only 16 of these had a concurrent inflammatory leukogram. Morphological changes included heterophil left-shifting with or without concurrent dysgranulopoiesis, toxicity, or hypersegmentation, reactive lymphocytes, plasma cells, and/or vacuolated monocytes. Although the observed leukocyte morphological changes are non-specific, their early recognition upon blood film evaluation may provide important, clinically-relevant information, particularly if the leukogram is normal. This case series is the first description of qualitative morphological changes in the leukocytes of elephants in association with inflammation.

  5. Complement Activation Induces Neutrophil Adhesion and Neutrophil-Platelet Aggregate Formation on Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Magdalena Riedl

    2017-01-01

    Discussion: Therefore, our findings of (i neutrophils adhering to complement-activated endothelial cells, (ii the formation of neutrophil-platelet aggregates on endothelial cells, and (iii the ability of aHUS serum to induce similar effects identify a possible role for neutrophils in aHUS manifestation.

  6. CONTENTS OF LYMPHOCYTE SUB-POPULATIONS IN THE CHILDREN WITH ACUTE LEUKEMIA AND LYMPHOMAS DEPENDENT ON INFECTIOUS COMPLICATION AND NEUTROPENIA

    Directory of Open Access Journals (Sweden)

    M. V. Peshikova

    2005-01-01

    Full Text Available Abstract. The aim of the present work was to evaluate the contents of some lymphocyte sub-populations in peripheral blood of the children with tumors of hematopoietic and lymphoid tissues, depending on infectious complication of cytostatic therapy and neutropenia. In all children undergoing cytostatic therapy for acute lympho-blastic leukemia and non-B cell non-Hodgkinґs lymphomas, we found significant decrease in the numbers of CD95 lymphocytes, absolute amounts of natural killer cells (CD16, CD56-lymphocytes and activated lymphocytes (СD11b, HLA-DR-cells, irrespective of neutrophile numbers in their blood and infectious complications. However, absolute number of CD25- lymphocytes was significantly decreased in the children with neutropenia. Relative contents of CD16, CD56, СD11b, HLA-DR, CD25-lymphocytes did not significantly differ from those in healthy children, or they were found to be significantly increased.

  7. The Role of Neutrophils in the Induction of Specific Th1 and Th17 during Vaccination against Tuberculosis.

    Science.gov (United States)

    Trentini, Monalisa M; de Oliveira, Fábio M; Kipnis, André; Junqueira-Kipnis, Ana P

    2016-01-01

    Mycobacterium tuberculosis causes tuberculosis (TB), a disease that killed more than 1.5 million people worldwide in 2014, and the Bacillus Calmette Guérin (BCG) vaccine is the only currently available vaccine against TB. However, it does not protect adults. Th1 and Th17 cells are crucial for TB control, as well as the neutrophils that are directly involved in DC trafficking to the draining lymph nodes and the activation of T lymphocytes during infection. Although several studies have shown the importance of neutrophils during M. tuberculosis infection, none have shown its role in the development of a specific response to a vaccine. The vaccine mc(2)-CMX was shown to protect mice against M. tuberculosis challenge, mainly due to specific Th1 and Th17 cells. This study evaluated the importance of neutrophils in the generation of the Th1- and Th17-specific responses elicited by this vaccine. The vaccine injection induced a neutrophil rich lesion with a necrotic central area. The IL-17 KO mice did not generate vaccine-specific Th1 cells. The vaccinated IL-22 KO mice exhibited Th1- and Th17-specific responses. Neutrophil depletion during vaccination abrogated the induction of Th1-specific responses and prohibited the bacterial load reduction observed in the vaccinated animals. The results show, for the first time, the role of neutrophils in the generation of specific Th1 and Th17 cells in response to a tuberculosis vaccine.

  8. The characteristics of peripheral blood leukocytes in persons working with ionizing radiation sources

    International Nuclear Information System (INIS)

    Zykova, I.A.; Sokolova, N.B.; Yas'kova, V.Z.

    1984-01-01

    Functional and qualitative changes of peripheral blood cellular composition were studied in persons working over a long period of time with ionizing radiation sources under the action of various factors of production upon an organism. Appression of a function and increase of T-lymphocyte chromosome damages were revealed against the background of a decrease both of enzymatic activity level and leukocyte number in persons operating for a long time (more than 10 years) with ionizing radiation sources. Discovered changes occurred under the action upon a human being not only of small doses of ionizing radiation but a whole complex of industrial factors which may initiate changes of adapted character

  9. Different innate neutrophil responses in controlled and uncontrolled asthma

    NARCIS (Netherlands)

    Tang, Francesca; Foxley, Gloria; Gibson, Peter; Burgess, Janette; Baines, Katherine; Oliver, Brian

    2015-01-01

    Introduction: Respiratory viruses are a major cause of asthma exacerbations. Neutrophilic inflammation occurs during infections and is associated with difficult to treat asthma. The role of neutrophils in viral infections and whether neutrophil dysfunction contributes to exacerbation pathogenesis

  10. SiMA: A simplified migration assay for analyzing neutrophil migration.

    Science.gov (United States)

    Weckmann, Markus; Becker, Tim; Nissen, Gyde; Pech, Martin; Kopp, Matthias V

    2017-07-01

    In lung inflammation, neutrophils are the first leukocytes migrating to an inflammatory site, eliminating pathogens by multiple mechanisms. The term "migration" describes several stages of neutrophil movement to reach the site of inflammation, of which the passage of the interstitium and basal membrane of the airway are necessary to reach the site of bronchial inflammation. Currently, several methods exist (e.g., Boyden Chamber, under-agarose assay, or microfluidic systems) to assess neutrophil mobility. However, these methods do not allow for parameterization on single cell level, that is, the individual neutrophil pathway analysis is still considered challenging. This study sought to develop a simplified yet flexible method to monitor and quantify neutrophil chemotaxis by utilizing commercially available tissue culture hardware, simple video microscopic equipment and highly standardized tracking. A chemotaxis 3D µ-slide (IBIDI) was used with different chemoattractants [interleukin-8 (IL-8), fMLP, and Leukotriene B4 (LTB 4 )] to attract neutrophils in different matrices like Fibronectin (FN) or human placental matrix. Migration was recorded for 60 min using phase contrast microscopy with an EVOS ® FL Cell Imaging System. The images were normalized and texture based image segmentation was used to generate neutrophil trajectories. Based on these spatio-temporal information a comprehensive parameter set is extracted from each time series describing the neutrophils motility, including velocity and directness and neutrophil chemotaxis. To characterize the latter one, a sector analysis was employed enabling the quantification of the neutrophils response to the chemoattractant. Using this hard- and software framework we were able to identify typical migration profiles of the chemoattractants IL-8, fMLP, and LTB 4 , the effect of the matrices FN versus HEM as well as the response to different medications (Prednisolone). Additionally, a comparison of four asthmatic and

  11. Frontline Science: HMGB1 induces neutrophil dysfunction in experimental sepsis and in patients who survive septic shock.

    Science.gov (United States)

    Grégoire, Murielle; Tadié, Jean-Marc; Uhel, Fabrice; Gacouin, Arnaud; Piau, Caroline; Bone, Nathaniel; Le Tulzo, Yves; Abraham, Edward; Tarte, Karin; Zmijewski, Jaroslaw W

    2017-06-01

    Sepsis is accompanied by the initial activation of proinflammatory pathways and long-lasting immunosuppression that appears to contribute to late-occurring mortality. Although high-mobility group box 1 (HMGB1) is involved in many aspects of inflammation, its role in sepsis-induced immune suppression remains unclear. In this study, we examined HMGB1's contribution to neutrophil NADPH oxidase activity dysfunction and associated neutrophil-dependent bacterial clearance in mice subjected to sepsis and in patients who survive septic shock. Using a murine model of polymicrobial septic peritonitis, we demonstrated that treatment with anti-HMGB1 Ab significantly diminished sepsis-induced dysfunction of neutrophil NADPH oxidase activity. In a subsequent set of experiments, we found that blocking HMGB1 preserved the ability of neutrophils from patients recovering from septic shock to activate NADPH oxidase. Taken together, our data suggest that HMGB1 accumulation in the late phase of sepsis plays a specific role in the development of postsepsis immunosuppression and specifically affects neutrophil-dependent antibacterial defense mechanisms. Thus, blocking HMGB1 may be a promising therapeutic intervention to diminish the adverse effects of sepsis-induced immunosuppression. © Society for Leukocyte Biology.

  12. The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

    Directory of Open Access Journals (Sweden)

    Pedro Xavier-Elsas

    2015-01-01

    Full Text Available Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp- deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

  13. Oral neutrophil responses to acute prolonged exercise may not be representative of blood neutrophil responses.

    Science.gov (United States)

    Davison, Glen; Jones, Arwel Wyn

    2015-03-01

    Neutrophil numbers and function (oxidative burst) were assessed in peripheral blood and oral samples before and after prolonged exercise. Blood neutrophil count increased (∼3.5-fold, P < 0.001) and function decreased (30% ± 19% decrease, P = 0.005) postexercise. Oral neutrophil count (P = 0.392) and function (P = 0.334) were unchanged. Agreement between oral and blood neutrophil function responses to exercise was poor. These findings highlight the importance of studying neutrophils within various compartments/sample types.

  14. Neutrophil migration under normal and sepsis conditions.

    Science.gov (United States)

    Lerman, Yelena V; Kim, Minsoo

    2015-01-01

    Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

  15. Candida albicans escapes from mouse neutrophils

    DEFF Research Database (Denmark)

    Ermert, David; Niemiec, Maria J; Röhm, Marc

    2013-01-01

    is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed...

  16. Neutrophils: potential therapeutic targets in tularemia?

    Directory of Open Access Journals (Sweden)

    Lee-Ann H Allen

    2013-12-01

    Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

  17. Distribution, recovery and concentration of platelets and leukocytes in L-PRP prepared by centrifugation.

    Science.gov (United States)

    de Melo, Bruna Alice Gomes; Martins Shimojo, Andréa Arruda; Marcelino Perez, Amanda Gomes; Duarte Lana, José Fabio Santos; Andrade Santana, Maria Helena

    2018-01-01

    Platelet-rich plasma (PRP) is an autologous product prepared from whole blood (WB) that is widely used in regenerative medicine. In clinical practice, discontinuous centrifugation is used for both hand- and machine-prepared PRP. However, separation of WB fractions via centrifugation is a complex process, and the lack of clear mechanisms limits the understanding and evaluation of PRP preparation methods This paper focuses on the distribution, recovery and concentration factor of platelets and leukocytes in L-PRP (leukocyte and platelet-rich plasma) to define a concentration pattern for these blood components due to centrifugation conditions. WB collected from three healthy donors was centrifuged for 10min at 50-800 xg in a first step and then at 400 xg in a second step. The results from the first centrifugation step showed most platelets to be distributed in the upper layer (UL) and the buffy coat (BC), with approximately 14.5±5.2% retained in the bottom layer (BL). Most leukocytes were present in the BL. The greatest platelet recoveries from L-PRP were obtained at up to 150 xg (88.5±16.9%). The cumulative concentration factors with respect to the WB from the second centrifugation step were 6 and 1.2 for platelets and leukocytes, respectively. Thus, the concentration patterns delineated three centrifugation ranges with platelet/leukocyte ratios of 205±18, 325±15 and 107±4 and lymphocyte/granulocyte ratios of 1.54±0.74, 0.90±0.08 and 0.42±0.07. These findings contribute to a scientifically based standardization of L-PRP preparations. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance.

    Science.gov (United States)

    Robertson, Charles M; Perrone, Erin E; McConnell, Kevin W; Dunne, W Michael; Boody, Barrett; Brahmbhatt, Tejal; Diacovo, M Julia; Van Rooijen, Nico; Hogue, Lisa A; Cannon, Carolyn L; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2008-12-01

    Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare. We examined the pathogenicity of four different strains of S. aureus (both methicillin-sensitive and -resistant as well as Panton-Valentine leukocidin-positive and -negative) in four strains of immunocompetent inbred and outbred mice (FVB/N, C57Bl/6, BALB/c, ND4; n = 148). The immunological basis for the development of murine S. aureus pneumonia was then determined by selectively depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset of infection. An additional cohort of animals was rendered immunosuppressed by induction of abdominal sepsis via cecal ligation and puncture 2, 4, or 7 d prior to the onset of pneumonia. Nearly all immunocompetent mice survived, regardless of which strain of S. aureus was used or which strain of mouse was infected. Among animals with immune depletion or prior immunosuppression, survival was decreased only following neutrophil depletion (26% versus 90% alive at 7 d, P < 0.0001). Compared to immunocompetent animals, neutrophil-depleted mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and 40 h but had no difference in levels of bacteremia. Neutrophil-depleted mice also had elevated levels of pulmonary monocyte chemotactic protein-1 (822 pg/mL versus 150 pg/mL, P < 0.05). In contrast, pulmonary histological appearance was similar in both groups as was dry/wet lung weight. These results suggest that neutrophils play a critical role in the host response to S. aureus pneumonia, and the survival differences observed in neutrophil-depleted mice are associated with alterations in bacterial clearance and pulmonary cytokine response.

  19. Leukocyte subtype counts and its association with vascular structure and function in adults with intermediate cardiovascular risk. MARK study.

    Directory of Open Access Journals (Sweden)

    Leticia Gomez-Sanchez

    Full Text Available We investigated the relationship between leukocyte subtype counts and vascular structure and function based on carotid intima-media thickness, pulse wave velocity, central augmentation index and cardio-ankle vascular index by gender in intermediate cardiovascular risk patients.This study analyzed 500 subjects who were included in the MARK study, aged 35 to 74 years (mean: 60.3±8.4, 45.6% women.Brachial ankle Pulse Wave Velocity (ba-PWV estimate by equation, Cardio-AnkleVascular Index (CAVI using the VaSera device and Carotid ultrasound was used to measure carotid Intima Media Thickness (IMT. The Mobil-O-Graph was used to measure the Central Augmentation Index (CAIx.Total leukocyte, neutrophil and monocyte counts were positively correlated with IMT (p < 0.01 in men. Monocyte count was positively correlated with CAIx in women (p < 0.01. In a multiple linear regression analysis, the IMT mean maintained a positive association with the neutrophil count (β = 1.500, p = 0.007 in men. CAIx maintained a positive association with the monocyte count (β = 2.445, p = 0.022 in women.The results of this study suggest that the relationship between subtype circulating leukocyte counts and vascular structure and function, although small, may be different by gender. In men, the neutrophil count was positively correlated with IMT and in women, the monocyte count with CAIx, in a large sample of intermediate-risk patients. These association were maintained after adjusting for age and other confounders.ClinicalTrials.gov NCT01428934.

  20. Contribution of neutrophils to acute lung injury.

    Science.gov (United States)

    Grommes, Jochen; Soehnlein, Oliver

    2011-01-01

    Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

  1. The complex interplay between neutrophils and cancer.

    Science.gov (United States)

    Rakic, Andrea; Beaudry, Paul; Mahoney, Douglas J

    2018-03-01

    Neutrophils are the most abundant type of white blood cell, and are an essential component of the innate immune system. They characteristically arrive rapidly at sites of infection and injury, and release a variety of cytokines and toxic molecules to eliminate pathogens and elicit an acute inflammatory response. Research into the function of neutrophils in cancer suggest they have divergent roles. Indeed, while most studies have found neutrophils to be associated with cancer progression, others have also documented anticancer effects. In this review, we describe the investigations into neutrophil populations that have been implicated in promoting tumor growth and metastasis as well those demonstrating antitumor functions. The collective research suggests a complex role for neutrophils in cancer biology, which raises the prospect of their targeting for the treatment of cancer.

  2. Lymphocyte electrotaxis in vitro and in vivo.

    Science.gov (United States)

    Lin, Francis; Baldessari, Fabio; Gyenge, Christina Crenguta; Sato, Tohru; Chambers, Robert D; Santiago, Juan G; Butcher, Eugene C

    2008-08-15

    Electric fields are generated in vivo in a variety of physiologic and pathologic settings, including penetrating injury to epithelial barriers. An applied electric field with strength within the physiologic range can induce directional cell migration (i.e., electrotaxis) of epithelial cells, endothelial cells, fibroblasts, and neutrophils suggesting a potential role in cell positioning during wound healing. In the present study, we investigated the ability of lymphocytes to respond to applied direct current (DC) electric fields. Using a modified Transwell assay and a simple microfluidic device, we show that human PBLs migrate toward the cathode in physiologically relevant DC electric fields. Additionally, electrical stimulation activates intracellular kinase signaling pathways shared with chemotactic stimuli. Finally, video microscopic tracing of GFP-tagged immunocytes in the skin of mouse ears reveals that motile cutaneous T cells actively migrate toward the cathode of an applied DC electric field. Lymphocyte positioning within tissues can thus be manipulated by externally applied electric fields, and may be influenced by endogenous electrical potential gradients as well.

  3. Human neutrophils in auto-immunity.

    Science.gov (United States)

    Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

    2016-04-01

    Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Expression of IL-17A concentration and effector functions of peripheral blood neutrophils in food allergy hypersensitivity patients.

    Science.gov (United States)

    Żbikowska-Gotz, Magdalena; Pałgan, Krzysztof; Gawrońska-Ukleja, Ewa; Kuźmiński, Andrzej; Przybyszewski, Michał; Socha, Ewa; Bartuzi, Zbigniew

    2016-03-01

    Lymphocytes Th17 and other types of immune system cells produce IL17. By induction of cytokines and chemokines, the IL17 cytokine is involved in mechanisms of allergic reaction with participation of neutrophil granulocytes. It affects activation, recruitment, and migration of neutrophils to the tissues, regulating inflammatory reaction intensity. Excited neutrophils secrete inter alia elastase and reactive oxygen species (ROS)--significant mediators of inflammation process responsible for tissues damage.The aim of the study was to evaluate the concentrations of serum interleukin 17A, serum neutrophil elastase, and ROS production by neutrophils in patients with food allergy.The study included 30 patients with food allergy diagnosed based on interview, clinical symptoms, positive SPT, placebo controlled double-blind oral provocation trial, and the presence of asIgE in blood serum against selected food allergens using fluoro-immuno-enzymatic method FEIA UNICap 100. The control group consisted of 10 healthy volunteers. The concentrations of IL17A were determined in all patients using ELISA method with eBioscience kits, and elastase using BenderMed Systems kits. Chemiluminescence of non-stimulated neutrophils was evaluated using luminol-dependent kinetic method for 40 min on Luminoskan (Labsystems luminometer).The results of serum IL-17A concentrations and the values of chemiluminescence obtained by non-activated neutrophils, as well as elastase concentrations, were higher in patients with food allergic hypersensitivity compared to healthy volunteers.This study demonstrates a significance of IL-17A and activated neutrophil granulocytes in the course of diseases with food allergic hypersensitivity. © The Author(s) 2015.

  5. High IFN-alpha responses associated with depletion of lymphocytes and natural IFN-producing cells during classical swine fever

    NARCIS (Netherlands)

    Summerfield, A.; Alves, M.; Ruggli, N.; Bruin, de M.G.M.; McCullough, K.C.

    2006-01-01

    During the acute phase of the viral hemorrhagic disease, classical swine fever (CSF), a severe hematologic depletion in primary lymphoid organs and depletion of peripheral blood T and B lymphocytes are observed. The onset of these pathologic events is before viremia and independent of leukocyte

  6. Significance of leukocyte scanning in infected endoprostheses

    Energy Technology Data Exchange (ETDEWEB)

    Becker, W.; Pasurka, B.; Boerner, W.

    1989-03-01

    31 patients with suspected septic loosening of an endoprosthesis (hip endoprosthesis n=30; knee endoprosthesis n=1) were examined with leukocyte scans (10 MBq /sup 111/In-oxine: n=22; 300 MBq /sup 99m/Tc-HMPAO: n=9). The results were compared with results of the bacterial growth (n=22), the histology (n=12) and of the bone scans (/sup 99m/Tc-MDP: n=20) which were performed within 4 days. The sensitivity of the bone scan was 100%, the specificity 30% and the diagnostic accuracy regarding a septic loosening of the arthroplasty was 55%. For the leukocyte scans a comparable sensitivity of 100%, but a higher specificity (86%) and accuracy (91%) could be calculated. A false positive leukocyte scan could be observed in a periprosthetic granuloma, an ossifying periarthritis and in a patient with negative bacterial growth with the histological proof of an inflammation.

  7. Leukocyte scintiscanning for the diagnosis of inflammations

    International Nuclear Information System (INIS)

    Becker, W.

    1988-01-01

    The value of leukocyte scintiscanning for clinical diagnostics is examined with regard to various areas of indications, and as a method of first examination, or as an alternative to, or additional method to be combined with, the other usual techniques. Leukocyte scintiscanning is indicated as a good first examination method in case of chronic enteritis in a highly active stage, stenosis of the colon, or when abscess is suspected, or infected renal cysts, or infection of angioplasty, osteomyelitis, or in case of fiever of unknown origin and impossible focal diagnosis. It also is applicable for follow-up diagnostics in chronic enteritis, suspected abdominal abscess, prosthetic valvular endocarditis, and infection of hip joint prothesis. The method also may yield additional information in case of renal graft rejection, coronary inflammations, for differential diagnosis of brain tumor or abcess, edematous or antodigestive pancreatitis, and in chronic polyarthritis. For leukocyte labelling, indium-111 and Tc-99m are primarily used. (ECB) [de

  8. Lipid raft-associated β-adducin is required for PSGL-1-mediated neutrophil rolling on P-selectin.

    Science.gov (United States)

    Xu, Tingshuang; Liu, Wenai; Yang, Chen; Ba, Xueqing; Wang, Xiaoguang; Jiang, Yong; Zeng, Xianlu

    2015-02-01

    Lipid rafts, a liquid-ordered plasma membrane microdomain, are related to cell-surface receptor function. PSGL-1, a major surface receptor protein for leukocyte, also acts as a signaling receptor in leukocyte rolling. To investigate the role of lipid raft in PSGL-1 signaling in human neutrophils, we quantitatively analyzed lipid raft proteome of human promyelocytic leukemia cell line HL-60 cells and identified a lipid raft-associated protein β-adducin. PSGL-1 ligation induced dissociation of the raft-associated protein β-adducin from lipid rafts and actin, as well as phosphorylation of β-adducin, indicating a transient uncoupling of lipid rafts from the actin cytoskeleton. Knockdown of β-adducin greatly attenuated HL-60 cells rolling on P-selectin. We also showed that Src kinase is crucial for PSGL-1 ligation-induced β-adducin phosphorylation and relocation. Taken together, these results show that β-adducin is a pivotal lipid raft-associated protein in PSGL-1-mediated neutrophil rolling on P-selectin. © Society for Leukocyte Biology.

  9. Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils.

    Science.gov (United States)

    Qiu, F H; Devchand, P R; Wada, K; Serhan, C N

    2001-12-01

    Aspirin-triggered 15-epi-lipoxin A4 (ATL) is an endogenous lipid mediator that mimics the actions of native lipoxin A4, a putative "stop signal" involved in regulating resolution of inflammation. A metabolically more stable analog of ATL, 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4 analog (ATLa), inhibits neutrophil recruitment in vitro and in vivo and displays potent anti-inflammatory actions. ATLa binds with high affinity to the lipoxin A4 receptor, a G protein-coupled receptor on the surface of leukocytes. In this study, we used freshly isolated human neutrophils to examine ATLa's potential for initiating rapid nuclear responses. Using differential display reverse transcription polymerase chain reaction, we identified a subset of genes that was selectively up-regulated upon short exposure of polymorphonuclear leukocytes to ATLa but not to the chemoattractant leukotriene B4 or vehicle alone. We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid-responsive gene in hamster smooth muscle cells. Treatment of human neutrophils with pertussis toxin blocked ATLa up-regulation of NAB1. In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo. These findings provide evidence for rapid transcriptional induction of a cassette of genes via an ATLa-stimulated G protein-coupled receptor pathway that is potentially protective and overlaps with the anti-inflammatory glucocorticoid regulatory circuit.

  10. Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

    Science.gov (United States)

    Gritti, Nicola; Caccia, Michele; Sironi, Laura; Collini, Maddalena; D'Alfonso, Laura; Granucci, Francesca; Zanoni, Ivan; Chirico, Giuseppe

    2013-01-01

    The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase) upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.

  11. Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

    Directory of Open Access Journals (Sweden)

    Nicola Gritti

    Full Text Available The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.

  12. Activation of bovine neutrophils by Brucella spp.

    Science.gov (United States)

    Keleher, Lauren L; Skyberg, Jerod A

    2016-09-01

    Brucellosis is a globally important zoonotic infectious disease caused by gram negative bacteria of the genus Brucella. While many species of Brucella exist, Brucella melitensis, Brucella abortus, and Brucella suis are the most common pathogens of humans and livestock. The virulence of Brucella is largely influenced by its ability to evade host factors, including phagocytic killing mechanisms, which are critical for the host response to infection. The aim of this study was to characterize the bovine neutrophil response to virulent Brucella spp. Here, we found that virulent strains of smooth B. abortus, B. melitensis, B. suis, and virulent, rough, strains of Brucella canis possess similar abilities to resist killing by resting, or IFN-γ-activated, bovine neutrophils. Bovine neutrophils responded to infection with a time-dependent oxidative burst that varied little between Brucella spp. Inhibition of TAK1, or SYK kinase blunted the oxidative burst of neutrophils in response to Brucella infection. Interestingly, Brucella spp. did not induce robust death of bovine neutrophils. These results indicate that bovine neutrophils respond similarly to virulent Brucella spp. In addition, virulent Brucella spp., including naturally rough strains of B. canis, have a conserved ability to resist killing by bovine neutrophils. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. IL-17 and γδ T-lymphocytes play a critical role in innate immunity against Nocardia asteroides GUH-2

    Science.gov (United States)

    Tam, Stanley; Maksaereekul, Saipiroon; Hyde, Dallas M.; Godinez, Ivan; Beaman, Blaine L.

    2012-01-01

    The early host response during pulmonary nocardiosis is highly dependent on neutrophils and the successful clearance of bacteria in tissue. The data presented in this study showed that IL-17 mediated the neutrophil response following intranasal inoculation with Nocardia asteroides strain GUH-2. Flow cytometry revealed that neutrophil levels in C57BL/6 mice were increased by day 1 post inoculation and remained elevated until day 3, during which time the majority of bacterial clearance occurred. Intracellular cytokine staining for IL-17 showed a 3.5- to 5-fold increase in IL-17 producing T-lymphocytes that were predominately comprised by CD4−CD8− γδ T-lymphocytes. The importance of IL-17 and γδ T-cells was determined by the in vivo administration of antibody, capable of blocking IL-17 binding or TCR δ, respectively. Neutralization of either IL-17 or γδ T-cells in Nocardia treated mice resulted in attenuated neutrophil infiltration. Paralleling this impaired neutrophil recruitment, nearly a 10-fold increase in bacterial burden was observed in both anti-IL-17 and anti-TCR δ treated animals. Together, these data indicate a protective role for IL-17 and suggest that IL-17 producing γδ T-lymphocytes contribute to neutrophil infiltration during pulmonary nocardiosis. PMID:22634423

  14. Mechanism of subdural effusion evolves into chronic subdural hematoma: IL-8 inducing neutrophil oxidative burst.

    Science.gov (United States)

    Tao, Zhiqiang; Lin, Yingying; Hu, Maotong; Ding, Shenghong; Li, Jianwei; Qiu, Yongming

    2016-01-01

    Chronic subdural hematoma (CSDH) is still a mysterious disease. Though great success has been has achieved by neuro-surgery treatment, the origin and development of CSDH remains unknown. Tremendous clinical observations have found the correlation of subdural effusion (SDE) and CSDH. However, systematic elucidation of CSDH's origin and progression is lacking while almost all the current hypothesis only explained partial phenomenon. This hypothesis proposes Interleukin (IL)-8 inducing neutrophil respiratory burst is the crucial impact when SDE evolves into CSDH. IL-8 initially secreted by dural border layer cells, accumulates and the concentration of IL-8 rises in the SDE cavity. Accompanied by the formation of neo-membrane under the dura meninges, IL-8 firstly prompts to establish the neo-vasculature in it, and then attracts lymphocytes aggregation in the neo-membrane. Both the newly recruited lymphocytes and endothelial cells assist the further elevation of local IL-8 concentration. When the IL-8 concentration elevated to a particular level, it attracts neutrophils to the inner wall of neo-vessels and primes them to oxidative burst. Lysosomes and superoxide released by these neutrophils make the fragile neo-capillary became leaky, and subsequently the plasma and blood cells run into SDE. However, as long as the erythrocytes come into the cavity, they shall bind large quantity of IL-8 and decrease IL-8 concentration to a lower level relatively that reduce the neutrophils recruit. When this negative feedback is stagnancy, for example, the SDE space is so large in elder man who is experiencing brain atrophy, the neo-vessels have to release more erythrocytes to bind IL-8, the liquid cavity will expand and the high intracranial pressure symptoms appeared. Our hypothesis holds potential for the proper therapeutic intervention of CSDH. IL-8 antagonist and other anti-inflammation drugs like macrolides antibiotics, glucocorticoid and atorvastatin might be optional to resist

  15. Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

    Science.gov (United States)

    Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

    2014-04-11

    Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

  16. Leukocyte profiles for western fence lizards, Sceloporus occidentalis, naturally infected by the malaria parasite Plasmodium mexicanum.

    Science.gov (United States)

    Motz, Victoria L; Lewis, William D; Vardo-Zalik, Anne M

    2014-10-01

    Plasmodium mexicanum is a malaria parasite that naturally infects the western fence lizard, Sceloporus occidentalis , in northern California. We set out to determine whether lizards naturally infected with this malaria parasite have different leukocyte profiles, indicating an immune response to infection. We used 29 naturally infected western fence lizards paired with uninfected lizards based on sex, snout-to-vent length, tail status, and the presence-absence of ectoparasites such as ticks and mites, as well as the presence-absence of another hemoparasite, Schellackia occidentalis. Complete white blood cell (WBC) counts were conducted on blood smears stained with Giemsa, and the proportion of granulocytes per microliter of blood was estimated using the Avian Leukopet method. The abundance of each WBC class (lymphocytes, monocytes, heterophils, eosinophils, and basophils) in infected and uninfected lizards was compared to determine whether leukocyte densities varied with infection status. We found that the numbers of WBCs and lymphocytes per microliter of blood significantly differed (P lizard's immune response to increase the levels of circulating WBCs, but what effect this has on the biology of the parasite remains unclear.

  17. Earthworm coelomocyte extracellular traps: structural and functional similarities with neutrophil NETs.

    Science.gov (United States)

    Homa, Joanna

    2018-03-01

    Invertebrate immunity is associated with natural mechanisms that include cellular and humoral elements, similar to those that play a role in vertebrate innate immune responses. Formation of extracellular traps (ETs) is a newly discovered mechanism to combat pathogens, operating not only in vertebrate leucocytes but also in invertebrate immune cells. The ET components include extracellular DNA (exDNA), antimicrobial proteins and histones. Formation of mammalian ETs depends on enzymes such as neutrophil elastase, myeloperoxidase, the citrullination of histones and protease activity. It was confirmed that coelomocytes-immunocompetent cells of the earthworm Eisenia andrei-are also able to release ETs in a protease-dependent manner, dependent or independent of the formation of reactive oxygen species and rearrangement of the cell cytoskeleton. Similar to vertebrate leukocytes (e.g., neutrophil), coelomocytes are responsible for many immune functions like phagocytosis, cytotoxicity and secretion of humoral factors. ETs formed by coelomocyte analogues to neutrophil ETs consist of exDNA, histone H3 and attached to these structures proteins, e.g., heat shock proteins HSP27. The latter fact confirms that mechanisms of ET release are conserved in evolution. The study on Annelida adds this animal group to the list of invertebrates capable of ET release, but most importantly provides insides into innate mechanisms of ET formation in lower animal taxa.

  18. Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children.

    Directory of Open Access Journals (Sweden)

    Genoveva Keustermans

    Full Text Available Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D and cardiovascular disease (CVD. The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far. Here, we aim to establish the expression of adiponectin and leptin receptors on circulating immune cells in obese children pre and post-lifestyle intervention compared to normal weight control children.13 obese children before and after a 1-year lifestyle intervention were compared with an age and sex-matched normal weight control group of 15 children. Next to routine clinical and biochemical parameters, circulating adipokines were measured, and flow cytometric analysis of adiponectin receptor 1 and 2 (AdipoR1, AdipoR2 and leptin receptor expression on peripheral blood mononuclear cell subsets was performed.Obese children exhibited typical clinical and biochemical characteristics compared to controls, including a higher BMI-SD, blood pressure and circulating leptin levels, combined with a lower insulin sensitivity index (QUICKI. The 1-year lifestyle intervention resulted in stabilization of their BMI-SD. Overall, circulating leukocyte subsets showed distinct adipokine receptor expression profiles. While monocytes expressed high levels of all adipokine receptors, NK and iNKT cells predominantly expressed AdipoR2, and B-lymphocytes and CD4+ and CD8+ T-lymphocyte subsets expressed AdipoR2 as well as leptin receptor. Strikingly though, leukocyte subset numbers and adipokine receptor expression profiles were largely similar in obese children and controls. Obese children showed higher naïve B-cell numbers, and pre-intervention also

  19. Palmitoylated transmembrane adaptor proteins in leukocyte signaling

    Czech Academy of Sciences Publication Activity Database

    Štěpánek, Ondřej; Dráber, Peter; Hořejší, Václav

    2014-01-01

    Roč. 26, č. 5 (2014), s. 895-902 ISSN 0898-6568 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Leukocyte * Adaptor * Palmitoylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.315, year: 2014

  20. The effects of 3-methylcholanthrene on lymphocyte proliferation in the common carp (Cyprinus carpio L.)

    International Nuclear Information System (INIS)

    Reynaud, S.; Deschaux, P.

    2005-01-01

    The sensitivity of lymphocyte proliferation as bioindicator of pollution stress was evaluated in the common carp (Cyrinus carpio L.). The time course response of peripheral blood leukocyte proliferation in response or not to mitogens was measured from 1 to 7 days after peritoneal injection of 3-methylcholantrene (3-MC), and compared to the time course response of a highly sensitive biomarker, induction of cytochrome P450. 3-Methylcholanthrene (40 mg kg -1 ) inhibited both B- and T-lymphocyte proliferation in response to lipopolysaccharide (LPS) and concanavalin A (Con A). Studies with α-naphtofiavone, suggest the lack of metabolic processes. 3-Methylcholanthrene alone strongly stimulated resting peripheral blood leukocytes (PBLs) proliferation. This effect was not transient. The induction of lymphocyte proliferation paralleled the increase in cytochrome P450 content in the liver. The specificity of polycyclic aromatic hydrocarbon (PAH)-induced lymphocyte proliferation suggests that this immune activity may be an early marker of exposure to PAHs in aquatic environments. The capacity of 3-MC to induce rapid lymphocyte proliferation may be related to PAH-induced rapid clonal expansion in mammals. These results strongly suggested that the underlying mechanism might be the same in both models. More studies are needed in fish to explain this phenomenon and may be helpful in understanding the occurrence of neoplastic epizootics in fish associated with PAH exposition

  1. Investigation of urinary neutrophil gelatinase associated lipocalin ...

    African Journals Online (AJOL)

    Investigation of urinary neutrophil gelatinase associated lipocalin (NGAL) for early diagnosis of acute kidney ... African Journal of Urology ... Demographic and clinical data including surgical procedure were recorded in Excel and analyzed by ...

  2. Leukocyte adhesion deficiency syndrome: report on the first case in Chile and South America

    Directory of Open Access Journals (Sweden)

    Rodrigo Vásquez-De Kartzow

    Full Text Available CONTEXT: Adhesion molecule deficiency type 1 is a rare disease that should be suspected in any patient whose umbilical cord presents delay in falling off, and who presents recurrent severe infections. Early diagnostic suspicion and early treatment improve the prognosis. CASE REPORT: The case of a four-month-old boy with recurrent hospitalizations because of severe bronchopneumonia and several episodes of acute otitis media with non-purulent drainage of mucus and positive bacterial cultures is presented. His medical history included neonatal sepsis and delayed umbilical cord detachment. Laboratory studies showed marked leukocytosis with predominance of neutrophils and decreased CD11b and CD18. These were all compatible with a diagnosis of leukocyte adhesion deficiency type I [LAD type 1].

  3. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... that may increase the risk of acute lymphocytic leukemia include: Previous cancer treatment. Children and adults who've had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased ... leukemia. Exposure to radiation. People exposed to very high ...

  4. Targeting Neutrophilic Inflammation using Polymersome-Mediated Cellular Delivery

    OpenAIRE

    Robertson, J.D.; Ward, J.R.; Avila-Olias, M.; Battaglia, G.; Renshaw, S.A.

    2017-01-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In ...

  5. Cryptococcus neoformans modulates extracellular killing by neutrophils

    Directory of Open Access Journals (Sweden)

    Asfia eQureshi

    2011-09-01

    Full Text Available We recently established a key role for host sphingomyelin synthase (SMS in the regulation of the killing activity of neutrophils against Cryptococcus neoformans. In this work, we studied the effect of C. neoformans on the killing activity of neutrophils and whether SMS would still be a player against C. neoformans in immunocompromised mice lacking T and NK cells (Tgε26 mice. To this end, we analyzed whether C. neoformans would have any effect on neutrophil survival and killing in vitro and in vivo. We show that unlike C. albicans, neither the presence nor the capsule size of C. neoformans cells have any effect on neutrophil viability. Interestingly, melanized C. neoformans cells totally abrogated the killing activity of neutrophils. Next, we monitored how exposure of neutrophils to C. neoformans cells would interfere with any further killing activity of the medium and found that pre-incubation with live but not heat-killed fungal cells significantly inhibits further killing activity of the medium. We next studied whether activation of SMS at the site of C. neoformans infection is dependent on T and NK cells. Using matrix-assisted laser desorption-ionization (MALDI tissue imaging in infected lung we found that similarly to previous observations in the isogenic wild type CBA/J mice, SM 16:0 levels are significantly elevated at the site of infection in mice lacking T and NK cells but only at early time points. This study highlights that C. neoformans may negatively regulate the killing activity of neutrophils and that SMS activation in neutrophils appears to be partially independent of T and/or NK cells.

  6. Neutrophil extracellular trap formation in supragingival biofilms.

    Science.gov (United States)

    Hirschfeld, Josefine; Dommisch, Henrik; Skora, Philipp; Horvath, Gabor; Latz, Eicke; Hoerauf, Achim; Waller, Tobias; Kawai, Toshihisa; Jepsen, Søren; Deschner, James; Bekeredjian-Ding, Isabelle

    2015-01-01

    Oral biofilms are the causative agents of the highly prevalent oral diseases periodontitis and caries. Additionally, the host immune response is thought to play a critical role in disease onset. Neutrophils are known to be a key host response factor to bacterial challenge on host surfaces. Release of neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy has gained increasing attention in the past years. Here, we investigated the influx of neutrophils into the dental plaque and the ability of oral bacteria to trigger intra-biofilm release of NETs and intracellular proteins. Supragingival biofilms and whole saliva were sampled from systemically healthy subjects participating in an experimental gingivitis study. Biofilms were analysed by immunofluorescence followed by confocal and fluorescence microscopy. Moreover, concentrations of cytokines and immune-associated proteins in biofilm suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood were stimulated with twelve bacterial species isolated from cultured biofilms or with lipopolysaccharide to monitor NET formation. Neutrophils, NETs, neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G, cathelicidin LL-37), interleukin-8, interleukin-1β and tumor necrosis factor were detected within plaque samples and saliva. All tested bacterial species as well as the polymicrobial samples isolated from the plaque of each donor induced release of NETs and interleukin-8. The degree of NET formation varied among different subjects and did not correlate with plaque scores or clinical signs of local inflammation. Our findings indicate that neutrophils are attracted towards dental biofilms, in which they become incorporated and where they are stimulated by microbes to release NETs and immunostimulatory proteins. Thus, neutrophils and NETs may be involved in host biofilm control, although their specific role needs to be further elucidated. Moreover, inter

  7. Study of CD69 antigen expression and integrity of leukocyte cellular membrane in stored platelet concentrates following irradiation and treatment with Mirasol® PRT System.

    Science.gov (United States)

    Lachert, Elżbieta; Woźniak, Jolanta; Antoniewicz-Papis, Jolanta; Krzywdzińska, Agnieszka; Kubis, Jolanta; Mikołowska, Agata; Letowska, Magdalena

    2017-01-01

    Leukocytes in transfused blood components, particularly residual lymphocytes, have been shown to contribute to the occurrence of various adverse reactions. One of the most severe is transfusionassociated graft versus host disease (TA-GvHD) following transfusion of blood components contaminated with immunocompetent T lymphocytes. Irradiation is a routine method for protection against TA-GvHD. According to the literature, some pathogen reduction methods have also been proven effective for the inactivation of T lymphocytes, and so they may be considered as an alternative to irradiation. Comparison of CD69 antigen expression and the integrity of the leukocyte cellular membrane in stored platelet concentrates (PCs) following irradiation with the Gammacell 3000 Elan (Nordion Inc., Ottawa, Canada) and treatment with the Mirasol® Pathogen Reduction Technology (PRT) System (Terumo BCT, Lakewood, USA). The study included seven experiments. For each experiment we used 3 PCs, for Mirasol® PRT System treatment (M), for Gammacell 3000 Elan irradiation (R), and for the control (C). 7-amino-actinomycin D (7-AAD, Becton Dickinson, Franklin Lakes, USA) permeability was used to determine lymphocyte viability while CD69 antigen expression was the marker of lymphocyte activation. Analyses of 7-AAD and CD69 antigen expression were performed in a FACS Canto I flow cytometer (Becton Dickinson, USA). During 6 storage days, viable lymphocyte count decreased to 28% (p = 0.001) in the Mirasol® PRT System treated PCs and to 65% (p = 0.004) in the irradiated PCs. A statistically significant increase in CD69 expression in the irradiated PCs was observed; 1.3-fold on day 3 and 1.5-fold on day 6. In the Mirasol ® PRT System treated PCs, no statistically significant increase was observed. The in vitro results suggest that the Mirasol® PRT System is as effective as irradiation due to donor leukocyte inactivation capacity.

  8. A [3H]- thymidine paper strip method for stimulation of lymphocytes. 2

    International Nuclear Information System (INIS)

    Schuett, C.; Goecke, H.; Schulze, H.A.; Westphal, H.J.; Glawe, H.J.

    1979-01-01

    Only 1 - 2 ml of heparinized peripheral blood are necessary for nitrogen and antigen testing, resp. Disturbing influences by the erythrocytes of the whole blood could not be observed neither in processing the blood cell culture nor in paper strip counting. However, the leukocyte/erythrocyte ratio influenced the blastogenesis in vitro. Provided the lymphocyte count remains constant, the storage of the whole blood is possible for 24 hours at 4 0 C

  9. Prevention of alloimmunization by ultraviolet-B irradiation. Inactivation of leukocytes and the generation of active oxygen and radicals

    International Nuclear Information System (INIS)

    Takahashi, Tsuneo; Mogi, Yuko; Sekiguchi, Sadayoshi; Akasaka, Junichi; Kamo, Naoki; Kuwabara, Mikinori.

    1994-01-01

    UV-B irradiation of platelet concentrates (PC) has been tried in several institutes to inactivate leukocytes in PC and prevent alloimmunization on platelet transfusion. However, the mechanism of inactivation of leukocytes contaminating PC has not been fully understood. It is known that UV-B light is absorbed by photosensitizers in cells and produces active oxygen and radicals, such as singlet oxygen, superioxide anions and hydroxyl radicals. These active oxygen or radicals should injure cellular components and this could cause the suppression of cellular functions. In this study, we investigated the relationships among UV-B irradiation, free radical generation and leukocyte inactivation. We found the evidence that active oxygen and radicals were produced in peripheral blood mononuclear cells by UV-B irradiation. UV-B irradiation suppressed the stimulatory function of leukocytes in a mixed lymphocyte reaction (MLR), and the suppression depended on the dosage of UV-B. Even a low dosage of UV-B, 10 J/m 2 , could inhibit the MLR if the irradiated cells were incubated at 37degC for 24 hours before co-culture with responder cells. Treatments of cells with the exogenous singlet oxygen or superoxide anions also caused suppression of the stimulatory function in the MLR, inhibition of capping formation of HLA-DR antigens, and an increase of intracellular free Ca 2+ levels as did the UV-B treatment. These results indicate that the active oxygen or radicals generated in UV-B-irradiated leukocytes could be one of the causes of leukocyte inactivation. (author0

  10. Cell type-specific variations in the induction of hsp70 in human leukocytes by feverlike whole body hyperthermia.

    Science.gov (United States)

    Oehler, R; Pusch, E; Zellner, M; Dungel, P; Hergovics, N; Homoncik, M; Eliasen, M M; Brabec, M; Roth, E

    2001-10-01

    Fever has been associated with shortened duration and improved survival in infectious disease. The mechanism of this beneficial response is still poorly understood. The heat-inducible 70-kDa heat shock protein (Hsp70) has been associated with protection of leukocytes against the cytotoxicity of inflammatory mediators and with improved survival of severe infections. This study characterizes the induction of Hsp70 by feverlike temperatures in human leukocytes in vitro and in vivo. Using flow cytometry, Hsp70 expression was determined in whole blood samples. This approach eliminated cell isolation procedures that would greatly affect the results. Heat treatment of whole blood in vitro for 2 hours at different temperatures revealed that Hsp70 expression depends on temperature and cell type; up to 41 degrees C, Hsp70 increased only slightly in lymphocytes and polymorphonuclear leukocytes. However, in monocytes a strong induction was already seen at 39 degrees C, and Hsp70 levels at 41 degrees C were 10-fold higher than in the 37 degrees C control. To be as close as possible to the physiological situation during fever, we immersed healthy volunteers in a hot water bath, inducing whole body hyperthermia (39 degrees C), and measured leukocyte Hsp70 expression. Hsp70 was induced in all leukocytes with comparable but less pronounced cell type-specific variations as observed in vitro. Thus, a systemic increase of body temperature as triggered by fever stimulates Hsp70 expression in peripheral leukocytes, especially in monocytes. This fever-induced Hsp70 expression may protect monocytes when confronted with cytotoxic inflammatory mediators, thereby improving the course of the disease.

  11. In Vitro Evaluation of the Link Between Cell Activation State and Its Rheological Impact on the Microscale Flow of Neutrophil Suspensions

    Science.gov (United States)

    Akenhead, Michael L.; Horrall, Nolan M.; Rowe, Dylan; Sethu, Palaniappan; Shin, Hainsworth Y.

    2015-01-01

    Activated neutrophils have been reported to affect peripheral resistance, for example, by plugging capillaries or adhering to the microvasculature. In vivo and ex vivo data indicate that activated neutrophils circulating in the blood also influence peripheral resistance. We used viscometry and microvascular mimics for in vitro corroboration. The rheological impact of differentiated neutrophil-like HL-60 promyelocytes (dHL60s) or human neutrophil suspensions stimulated with 10 nM fMet-Leu-Phe (fMLP) was quantified using a cone-plate rheometer (450 s−1 shear rate). To evaluate their impact on microscale flow resistance, we used 10-μm Isopore® membranes to model capillaries as well as single 200 × 50 μm microchannels and networks of twenty 20 × 50 μm microfluidic channels to mimic noncapillary microvasculature. Stimulation of dHL60 and neutrophil populations significantly altered their flow behavior as evidenced by their impact on suspension viscosity. Notably, hematocrit abrogated the impact of leukocyte activation on blood cell suspension viscosity. In micropore filters, activated cell suspensions enhanced flow resistance. This effect was further enhanced by the presence of erythrocytes. The resistance of our noncapillary microvascular mimics to flow of activated neutrophil suspensions was significantly increased only with hematocrit. Notably, it was elevated to a higher extent within the micronetwork chambers compared to the single-channel chambers. Collectively, our findings provide supportive evidence that activated neutrophils passing through the microcirculation may alter hemodynamic resistance due to their altered rheology in the noncapillary microvasculature. This effect is another way neutrophil activation due to chronic inflammation may, at least in part, contribute to the elevated hemodynamic resistance associated with cardiovascular diseases (e.g., hypertension and hypercholesterolemia). PMID:26065495

  12. In Vitro Evaluation of the Link Between Cell Activation State and Its Rheological Impact on the Microscale Flow of Neutrophil Suspensions.

    Science.gov (United States)

    Akenhead, Michael L; Horrall, Nolan M; Rowe, Dylan; Sethu, Palaniappan; Shin, Hainsworth Y

    2015-09-01

    Activated neutrophils have been reported to affect peripheral resistance, for example, by plugging capillaries or adhering to the microvasculature. In vivo and ex vivo data indicate that activated neutrophils circulating in the blood also influence peripheral resistance. We used viscometry and microvascular mimics for in vitro corroboration. The rheological impact of differentiated neutrophil-like HL-60 promyelocytes (dHL60s) or human neutrophil suspensions stimulated with 10 nM fMet-Leu-Phe (fMLP) was quantified using a cone-plate rheometer (450 s(-1) shear rate). To evaluate their impact on microscale flow resistance, we used 10-μm Isopore® membranes to model capillaries as well as single 200 × 50 μm microchannels and networks of twenty 20 × 50 μm microfluidic channels to mimic noncapillary microvasculature. Stimulation of dHL60 and neutrophil populations significantly altered their flow behavior as evidenced by their impact on suspension viscosity. Notably, hematocrit abrogated the impact of leukocyte activation on blood cell suspension viscosity. In micropore filters, activated cell suspensions enhanced flow resistance. This effect was further enhanced by the presence of erythrocytes. The resistance of our noncapillary microvascular mimics to flow of activated neutrophil suspensions was significantly increased only with hematocrit. Notably, it was elevated to a higher extent within the micronetwork chambers compared to the single-channel chambers. Collectively, our findings provide supportive evidence that activated neutrophils passing through the microcirculation may alter hemodynamic resistance due to their altered rheology in the noncapillary microvasculature. This effect is another way neutrophil activation due to chronic inflammation may, at least in part, contribute to the elevated hemodynamic resistance associated with cardiovascular diseases (e.g., hypertension and hypercholesterolemia).

  13. Gene deletion of P-Selectin and ICAM-1 does not inhibit neutrophil infiltration into peritoneal cavity following cecal ligation-puncture

    Directory of Open Access Journals (Sweden)

    Hess Karen

    2004-07-01

    Full Text Available Abstract Background Neutrophil infiltration is one of the critical cellular components of an inflammatory response during peritonitis. The adhesion molecules, P-selectin and intercellular adhesion molecule (ICAM-1, mediate neutrophil-endothelial cell interactions and the subsequent neutrophil transendothelial migration during the inflammatory response. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy, suggesting that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the objective of this study was to determine the role of P-selectin and ICAM-1 in neutrophil infiltration into the peritoneal cavity during early and late phases of peritonitis. Methods Peritonitis was induced in both male wild-type and P-selectin/ICAM-1 double deficient (P/I null mice by cecal ligation-puncture (CLP. Peripheral blood and peritoneal lavage were collected at 6 and 24 hours after CLP. The total leukocyte and neutrophil contents were determined, and neutrophils were identified with the aid of in situ immunohistochemical staining. Comparisons between groups were made by applying ANOVA and student t-test analysis. Results CLP induced a severe inflammatory response associated with a significant leukopenia in both wild-type and P/I null mice. Additionally, CLP caused a significant neutrophil infiltration into the peritoneal cavity that was detected in both groups of mice. However, neutrophil infiltration in the P/I null mice at 6 hours of CLP was significantly lower than the corresponding wild-type mice, which reached a similar magnitude at 24 hours of CLP. In contrast, in peritonitis induced by intraperitoneal inoculation of 2% glycogen, no significant difference in neutrophil infiltration was observed between the P/I null and wild-type mice at 6 hours of peritonitis. Conclusions The data suggest that alternative adhesion pathway(s independent of P-selectin and ICAM

  14. Chemokines in the corpus luteum: Implications of leukocyte chemotaxis

    Directory of Open Access Journals (Sweden)

    Liptak Amy R

    2003-11-01

    Full Text Available Abstract Chemokines are small molecular weight peptides responsible for adhesion, activation, and recruitment of leukocytes into tissues. Leukocytes are thought to influence follicular atresia, ovulation, and luteal function. Many studies in recent years have focused attention on the characterization of leukocyte populations within the ovary, the importance of leukocyte-ovarian cell interactions, and more recently, the mechanisms of ovarian leukocyte recruitment. Information about the role of chemokines and leukocyte trafficking (chemotaxis during ovarian function is important to understanding paracrine-autocrine relationships shared between reproductive and immune systems. Recent advances regarding chemokine expression and leukocyte accumulation within the ovulatory follicle and the corpus luteum are the subject of this mini-review.

  15. In-111-labeled leukocyte scintigraphy in postoperative joint infection

    International Nuclear Information System (INIS)

    Ogawa, Yoji; Uetani, Masataka; Aziz, A.; Hayashi, Kuniaki

    2000-01-01

    To evaluate the role of In-111-labeled leukocyte scintigraphy in the patients with suspected postoperative joint infection, 41 scintigraphic examinations were performed in 24 patients. Scintigrams were interpreted by the degree of accumulation of labeled leukocytes, and were classified into 3 groups: positive, intermediate, and negative. In the cases of positive leukocyte scans, definite diagnosis of infection was made in all cases except one. In the cases of negative scans, there was no evidence of infection. In 13 cases, leukocyte scintigrams were interpreted in conjunction with bone scintigrams. Definite diagnosis of infection was made in all of the cases with positive combined leukocyte/bone scan, and there was no evidence of infection in cases with negative combined leukocyte/bone scan. This study demonstrates that In-111-labeled leukocyte scintigraphy is a useful method in diagnosis of postoperative joint infection, and accuracy of the examination improves when combined with bone scintigraphy. (author)

  16. Effect of leukocyte hydrolases on bacteria

    International Nuclear Information System (INIS)

    Cohen, D.; Michel, J.; Ferne, M.; Bergner-Rabinowitz, S.; Ginsburg, I.

    1979-01-01

    Leukocyte extracts, trypsin, and lysozyme are all capable of releasing the bulk of the LPS from S. typhi, S. typhimurium, and E. coli. Bacteria which have been killed by heat, ultraviolet irradiation, or by a variety of metabolic inhibitors and antibiotics which affect protein, DNA, RNA, and cell wall synthesis no longer yield soluble LPS following treatment with the releasing agents. On the other hand, bacteria which are resistant to certain of the antibiotics yield nearly the full amount of soluble LPS following treatment, suggesting that certain heatabile endogenous metabolic pathways collaborate with the releasing agents in the release of LPS from the bacteria. It is suggested that some of the beneficial effects of antibiotics on infections with gram-negative bacteria may be the prevention of massive release of endotoxin by leukocyte enzymes in inflammatory sites

  17. Aberrant leukocyte telomere length in Birdshot Uveitis.

    Science.gov (United States)

    Vazirpanah, Nadia; Verhagen, Fleurieke H; Rothova, Anna; Missotten, Tom O A R; van Velthoven, Mirjam; Den Hollander, Anneke I; Hoyng, Carel B; Radstake, Timothy R D J; Broen, Jasper C A; Kuiper, Jonas J W

    2017-01-01

    Birdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes. To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls. Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (PRTEL1. These findings suggest that BU is accompanied by significantly longer LTL.

  18. Abcess detection using radiocolloid-labelled-leukocytes

    International Nuclear Information System (INIS)

    Simon, J.; Auvergnat, J.C.; Armengaud, M.; Guiraud, R.; Le Net, R.; Auvergnat, R.

    1975-01-01

    The early detection of infections centres using labelled polynuclear neutrophile (LPN) as vector was investigated. The method was based on one of the physiological properties of this substance, its phagocytotic power towards colloidal sulphur particles labelled with pertechnetate-Tc 99m. The preliminary results of experiments on dogs are reported and confirm that centres of infection can be determined in experimental animals by the use of polynuclear neutrophiles labelled by phagocytosis. It seems that these results are really due to the presence of LPN in situ and not to simple inflammatory hyperhaemia or to an excess of free pertechnetate. The nature of the vector, tracer and lebelling agent, the quality of the results obtained and the harmlessness of the method warrant its clinical application in human beings [fr

  19. Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

    Science.gov (United States)

    Song, Hyun-Ouk; Ryu, Jae-Sook

    2013-08-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

  20. Blood leukocyte responses to extracorporeal circulation. 2. Medium term extracorporeal circulation without and with extracorporeal irradiation in normal and splenectomized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Szemere, P.; Fliedner, T.M. (Ulm Univ. (Germany, F.R.). Abt. Klinische Physiologie)

    1983-01-01

    Medium term (6-8 h) extracorporeal irradiation without and with irradiation of blood was performed in normal and splenectomized dogs to reveal the changes of blood leukocytes including CFU-C. A regular but transitory decrease of granulocytes and a longer lasting diminution of lymphocytes in the blood were observed. The CFU-C level became and mostly remained very low during the procedure. Splenectomy did not influence significantly the changes of peripheral leukocyte counts. No marked difference of leukocytes was seen in the blood samples taken from the arterial or venous side of the shunt or even from the cubital vein. Also, the irradiation did not produce any difference in the alterations of blood cell counts compared to those without irradiation. The possible explanations of these results are discussed.

  1. Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of theileria-induced leukocyte transformation

    KAUST Repository

    Hayashida, Kyoko

    2012-09-04

    We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmo-dium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at http://totdb.czc.hokudai.ac.jp/. 2012 Hayashida et al. T.

  2. Blood leukocyte responses to extracorporeal circulation. 3. Long term extracorporeal circulation without and with irradiation in normal and splenectomized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Szemere, P.; Fliedner, T.M. (Ulm Univ. (Germany, F.R.). Abt. Klinische Physiologie)

    1983-01-01

    Long term (12-48 h) extracorporeal circulation without and with irradiation of the blood was performed in normal and splenectomized dogs in order to observe the effect of these procedures on blood leukocyte counts including CFU-C. A transient granulocytopenia and a decrease of lymphocyte count were observed. The blood CFU-C level diminished to a very low level and remained low for the whole time of the experiments. There was no significant difference between the results of procedures with or without irradiation. The similar effect of a shortened tubing system on the blood leukocyte count is also reported. Heparin infusion alone did not decrease the peripheral CFU-C concentration. The possible explanations for the observed phenomena are discussed.

  3. Leukocyte Populations are Associated with Heart Rate Variability After a Triathlon

    Directory of Open Access Journals (Sweden)

    Cruz Germán Hernández

    2016-12-01

    Full Text Available The purpose of this study was to analyze cellular immune components and their association with heart rate variability in triathlon athletes. Twelve athletes were included (age 36.41 ± 5.57 years, body mass 81.84 ± 10.97 kg and blood samples were taken one week before, immediately, at 2 and 48 hours, and one week after competition. Total lymphocytes and their subpopulations, neutrophils, basophils, eosinophils and monocytes were analyzed. At the same time, heart rate variability was recorded for 30 minutes using Polar Team2®. A significant difference between lymphocyte subpopulations and heart rate variability was found in the different study periods. A positive correlation was found between total lymphocytes and rMSSD (r = .736, p <0.05, CD3+ and rMSSD (r = .785, p <0.05, and CD4+ and rMSSD (r = .795, p < 0.05 at the end of the competition. After one week of competition, a negative correlation was found between eosinophils and MRR, SDNN, pNN50, and rMSSD (p <0.01; and basophils and MRR, SDNN, pNN50, and rMSSD (p <0.01; while a positive correlation was found between CD19+ (B cells and pNN50 (r = .678, p <0.05. Our results suggest that it is possible to predict the effect of training with regard to the athlete's performance.

  4. Th1-Induced CD106 Expression Mediates Leukocytes Adhesion on Synovial Fibroblasts from Juvenile Idiopathic Arthritis Patients.

    Science.gov (United States)

    Maggi, Laura; Margheri, Francesca; Luciani, Cristina; Capone, Manuela; Rossi, Maria Caterina; Chillà, Anastasia; Santarlasci, Veronica; Mazzoni, Alessio; Cimaz, Rolando; Liotta, Francesco; Maggi, Enrico; Cosmi, Lorenzo; Del Rosso, Mario; Annunziato, Francesco

    2016-01-01

    This study tested the hypothesis that subsets of human T helper cells can orchestrate leukocyte adhesion to synovial fibroblasts (SFbs), thus regulating the retention of leukocytes in the joints of juvenile idiopathic arthritis (JIA) patients. Several cell types, such as monocytes/macrophages, granulocytes, T and B lymphocytes, SFbs and osteoclasts participate in joint tissue damage JIA. Among T cells, an enrichment of classic and non-classic Th1 subsets, has been found in JIA synovial fluid (SF), compared to peripheral blood (PB). Moreover, it has been shown that IL-12 in the SF of inflamed joints mediates the shift of Th17 lymphocytes towards the non-classic Th1 subset. Culture supernatants of Th17, classic and non-classic Th1 clones, have been tested for their ability to stimulate proliferation, and to induce expression of adhesion molecules on SFbs, obtained from healthy donors. Culture supernatants of both classic and non-classic Th1, but not of Th17, clones, were able to induce CD106 (VCAM-1) up-regulation on SFbs. This effect, mediated by tumor necrosis factor (TNF)-α, was crucial for the adhesion of circulating leukocytes on SFbs. Finally, we found that SFbs derived from SF of JIA patients expressed higher levels of CD106 than those from healthy donors, resembling the phenotype of SFbs activated in vitro with Th1-clones supernatants. On the basis of these findings, we conclude that classic and non-classic Th1 cells induce CD106 expression on SFbs through TNF-α, an effect that could play a role in leukocytes retention in inflamed joints.