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Sample records for circulating neutrophil numbers

  1. Hidden truth of circulating neutrophils (polymorphonuclear neutrophil function in periodontally healthy smoker subjects

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    Chitra Agarwal

    2016-01-01

    Full Text Available Context: Tobacco smoking is considered to be a major risk factor associated with periodontal disease. Smoking exerts a major effect on the protective elements of the immune response, resulting in an increase in the extent and severity of periodontal destruction. Aims: The aim of the present study was to assess viability and phagocytic function of neutrophils in circulating blood of the smokers and nonsmokers who are periodontally healthy. Settings and Design: Two hundred subjects in the mean range of 20–30 years of age were included in the study population. It was a retrospective study carried out for 6 months. Materials and Methods: Two hundred subjects were divided into four groups: 50 nonsmokers, 50 light smokers (15 cigarettes/day. Full mouth plaque index, sulcus bleeding index, and probing depths were measured. Percentage viability of circulating neutrophils and average number of phagocytosed Candida albicans were recorded. Statistical Analysis Used: Means and standard deviations were calculated from data obtained within the groups. Comparison between the smokers and nonsmokers was performed by Kruskal–Wallis ANOVA analysis. Comparison between smoker groups was performed using Mann–Whitney–Wilcoxon test. Results: Percentage viability of neutrophils was significantly less in heavy smokers (66.9 ± 4.0, moderate (76.6 ± 4.2, light smokers (83.1 ± 2.5 as compared to nonsmokers (92.3 ± 2.6 (P < 0.01. The ability of neutrophils to phagocytose, i.e., mean particle number was significantly less in light smokers (3.5 ± 0.5, moderate smokers (2.3 ± 0.5, and heavy smokers (1.4 ± 0.5 compared to nonsmokers (4.9 ± 0.7 (P < 0.01 with evidence of dose-response effect. Conclusions: Smoking significantly affects neutrophils viability and phagocytic function in periodontally healthy population.

  2. Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer

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    Jitka Y. Sagiv

    2015-02-01

    Full Text Available Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs. LDNs consist of both immature myeloid-derived suppressor cells (MDSCs and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

  3. In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice.

    Science.gov (United States)

    Ribeiro, André Luiz Teroso; Shimada, Ana Lúcia Borges; Hebeda, Cristina Bichels; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Filho, Walter Dos Reis Pereira; Santos, Alcinéa Meigikos Dos Anjos; de Lima, Wothan Tavares; Farsky, Sandra Helena Poliselli

    2011-10-01

    Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of β(2) and β(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ

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

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    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

  5. A gender difference in circulating neutrophils in malnourished patients with COPD

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    Sven Larsson

    2011-01-01

    Full Text Available Sven Larsson1, Anita Nordenson1, Pernilla Glader1, Shigemi Yoshihara2, Anders Lindén1, Frode Slinde31Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; 2Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan; 3Department of Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SwedenBackground: Circulating markers of inflammation in chronic obstructive pulmonary disease (COPD may correlate to disease progression and extrapulmonary complications such as malnourishment. However, surprisingly little is known about gender-related differences for circulating inflammatory markers in COPD.Purpose: To characterize differences in circulating markers of inflammation in malnourished female and male patients with COPD.Subjects: Thirty female and 11 male patients with a clinical diagnosis of COPD and malnourishment were examined. A group of control subjects without evidence of COPD was recruited for comparison of some variables.Methods: Blood samples were drawn, and the following parameters were studied: leukocytes and differential counts, C-reactive protein (CRP, tumor necrosis factor-α, interleukin (IL-6 and IL-8, myeloperoxidase (MPO, neutrophil elastase (NE, intracellular adhesion molecule-1, vascular endothelial adhesion molecule-1, and E-selectin.Results: The mean neutrophil concentration was significantly (P = 0.019 higher in female (4.5 × 109/L than in male patients with COPD (3.5 × 109/L and significantly higher than in female control subjects (3.1 × 109/L (P , 0.01, n = 85. The mean CRP values were considerably higher in female (4.9 mg/mL than in male patients with COPD (1.5 mg/mL, but the difference was not statistically significant (P = 0.20. The mean concentrations of IL-6 and IL-8 tended to be higher in female than in male patients with COPD, but these differences did not reach statistical

  6. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

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    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  7. Usefulness of circulating vascular endothelial growth factor and neutrophil elastase as diagnostic markers of disseminated intravascular coagulation in non-cancer patients

    OpenAIRE

    Joo, Shin Young; Kim, Ji-Eun; Kim, Ju Young; Han, Kyou-Sup; Kim, Hyun Kyung

    2010-01-01

    Background Disseminated intravascular coagulation (DIC) is characterized by platelet and neutrophil activation. Platelets are the major source of circulating vascular endothelial growth factor (VEGF). Endostatin, an anti-angiogenic factor, is a fragment of collagen that is released from the extracellular matrix via the active cleavage of neutrophil elastase, thereby increasing the circulating level of endostatin. Hypercoagulable conditions such as DIC may induce the release of VEGF and neutro...

  8. Isolated blunt chest injury leads to transient activation of circulating neutrophils

    OpenAIRE

    Visser, T.; Hietbrink, F.; Groeneveld, K. M.; Koenderman, L; Leenen, L.P.H.

    2010-01-01

    Introduction The acute respiratory distress syndrome (ARDS) is a severe and frequently seen complication in multi-trauma patients. ARDS is caused by an excessive innate immune response with a clear role for neutrophils. As ARDS is more frequently seen in trauma patients with chest injury, we investigated the influence of chest injury on the systemic neutrophil response and the development of ARDS. Materials and methods Thirteen patients with isolated blunt chest injury [abbreviated injury sco...

  9. Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum.

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    Schmitz, Veronica; Prata, Rhana Berto da Silva; Barbosa, Mayara Garcia de Mattos; Mendes, Mayara Abud; Brandão, Sheila Santos; Amadeu, Thaís Porto; Rodrigues, Luciana Silva; Ferreira, Helen; Costa, Fabrício da Mota Ramalho; Dos Santos, Jessica Brandão; Pacheco, Fabiana Dos Santos; Machado, Alice de Miranda; Nery, José Augusto da Costa; Hacker, Mariana de Andrea; Sales, Anna Maria; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes

    2016-08-01

    Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably

  10. Explicit Determinants of the RFPrLrR Circulant and RLPrFrL Circulant Matrices Involving Some Famous Numbers

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    Tingting Xu

    2014-01-01

    Full Text Available Circulant matrices may play a crucial role in solving various differential equations. In this paper, the techniques used herein are based on the inverse factorization of polynomial. We give the explicit determinants of the RFPrLrR circulant matrices and RLPrFrL circulant matrices involving Fibonacci, Lucas, Pell, and Pell-Lucas number, respectively.

  11. Exact Determinants of Some Special Circulant Matrices Involving Four Kinds of Famous Numbers

    OpenAIRE

    Xiaoyu Jiang; Kicheon Hong

    2014-01-01

    Circulant matrix family is used for modeling many problems arising in solving various differential equations. The RSFPLR circulant matrices and RSLPFL circulant matrices are two special circulant matrices. The techniques used herein are based on the inverse factorization of polynomial. The exact determinants of these matrices involving Perrin, Padovan, Tribonacci, and the generalized Lucas number are given, respectively.

  12. Exact Determinants of Some Special Circulant Matrices Involving Four Kinds of Famous Numbers

    Directory of Open Access Journals (Sweden)

    Xiaoyu Jiang

    2014-01-01

    Full Text Available Circulant matrix family is used for modeling many problems arising in solving various differential equations. The RSFPLR circulant matrices and RSLPFL circulant matrices are two special circulant matrices. The techniques used herein are based on the inverse factorization of polynomial. The exact determinants of these matrices involving Perrin, Padovan, Tribonacci, and the generalized Lucas number are given, respectively.

  13. Determinants, Norms, and the Spread of Circulant Matrices with Tribonacci and Generalized Lucas Numbers

    OpenAIRE

    Juan Li; Zhaolin Jiang; Fuliang Lu

    2014-01-01

    Circulant matrices play an important role in solving ordinary and partial differential equations. In this paper, by using the inverse factorization of polynomial of degree n, the explicit determinants of circulant and left circulant matrix involving Tribonacci numbers or generalized Lucas numbers are expressed in terms of Tribonacci numbers and generalized Lucas numbers only. Furthermore, four kinds of norms and bounds for the spread of these matrices are given, respectively.

  14. Determinants, Norms, and the Spread of Circulant Matrices with Tribonacci and Generalized Lucas Numbers

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    Juan Li

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving ordinary and partial differential equations. In this paper, by using the inverse factorization of polynomial of degree n, the explicit determinants of circulant and left circulant matrix involving Tribonacci numbers or generalized Lucas numbers are expressed in terms of Tribonacci numbers and generalized Lucas numbers only. Furthermore, four kinds of norms and bounds for the spread of these matrices are given, respectively.

  15. Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer

    International Nuclear Information System (INIS)

    Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer

  16. Neutrophils, from marrow to microbes

    DEFF Research Database (Denmark)

    Borregaard, Niels

    2010-01-01

    . Neutrophils circulate in the blood as dormant cells. At sites of infection, endothelial cells capture bypassing neutrophils and guide them through the endothelial cell lining whereby the neutrophils are activated and tuned for the subsequent interaction with microbes. Once in tissues, neutrophils kill...... microorganisms by microbicidal agents liberated from granules or generated by metabolic activation. As a final act, neutrophils can extrude stands of DNA with bactericidal proteins attached that act as extracellular traps for microorganisms....

  17. Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

    International Nuclear Information System (INIS)

    Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (3H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder

  18. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

    LENUS (Irish Health Repository)

    Harmon, D

    2012-02-03

    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol\\/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg\\/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

  19. Isolation and number of circulated primordial germ cells (circulated-PGCs on stages of embryonic development of Gaok chicken

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    Kostaman T

    2013-03-01

    Full Text Available Avian primordial germ cell (PGCs show a unique migration pathway during early development. During the early embryonic development, as soon as the formation of blood vessels, PGCs enter the circulatory system and migrate to the gonadal primordial. The aim of this study was to examine the number of circulated-PGCs from Gaok chicken at different developmental stages of embryo. One hundred fertile eggs were divided into 5 groups and incubated in a portable incubator at 38oC and humidity 60%. Hatching was set according to the embryonic development stage between 14-18. The blood collection was done through the dorsal aorta using micropipette under microscope. The collected blood was grouped based on the embryonic stages and placed on a 1.5 ml eppendorf tube which had been filled with 1.000 µl of Calcium and Magnesium-free phosphate buffered saline (PBS -. The PGCs were then purified using nycodenz density gradient centrifugation. The results showed that the average number of circulated-PGCs per embryo from Gaok chicken were significantly affected by the stage of embryonic development (P < 0.05. The number of circulated-PGCs at stages 14, 15, 16, 17 and 18 were 42.8 ± 8.9, 51.0 ± 5.8, 37.6 ± 5.9, 32.8 ± 3.6 and 32.6 ± 3.2, respectively. However, the number of circulated-PGCs was no different between stage of 17 and 18. At Gaok chicken, the number of circulated-PGCs reach the peak at stage 15, it is recommended that collection of PGCs embryonic chicken from blood circulation was the best on stage 15. This information is useful in efficiency production of germline chimera and to preserve PGCs of other Indonesian native chicken.

  20. Prediction of cloud droplet number in a general circulation model

    Energy Technology Data Exchange (ETDEWEB)

    Ghan, S.J.; Leung, L.R. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-04-01

    We have applied the Colorado State University Regional Atmospheric Modeling System (RAMS) bulk cloud microphysics parameterization to the treatment of stratiform clouds in the National Center for Atmospheric Research Community Climate Model (CCM2). The RAMS predicts mass concentrations of cloud water, cloud ice, rain and snow, and number concnetration of ice. We have introduced the droplet number conservation equation to predict droplet number and it`s dependence on aerosols.

  1. Neutrophil gene expression in rheumatoid arthritis.

    Science.gov (United States)

    Cross, Andrew; Bakstad, Denise; Allen, John C; Thomas, Luke; Moots, Robert J; Edwards, Steven W

    2005-10-01

    There is now a growing awareness that infiltrating neutrophils play an important role in the molecular pathology of rheumatoid arthritis. In part, this arises from the fact that neutrophils have potent cytotoxic activity, but additionally from the fact that inflammatory neutrophils can generate a number of cytokines and chemokines that can have a direct influence on the progress of an inflammatory episode. Furthermore, the molecular properties of inflammatory neutrophils are quite different from those normally found in the circulation. For example, inflammatory neutrophils, but not blood neutrophils, can express cell surface receptors (such as MHC Class II molecules and FcgammaRI) that dramatically alter the way in which these cells can interact with ligands to modulate immune function. Cytokine/chemokine expression and surface expression of these novel cell surface receptors is dependent upon the neutrophil responding to local environmental factors to selectively up-regulate the expression of key cellular components via signalling pathways coupled to transcriptional activation. However, major changes in the expression levels of some proteins are also regulated by post-translational modifications that alter rates of proteolysis, and hence changes in the steady-state levels of these molecules. PMID:16112850

  2. The Explicit Identities for Spectral Norms of Circulant-Type Matrices Involving Binomial Coefficients and Harmonic Numbers

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    Jianwei Zhou

    2014-01-01

    Full Text Available The explicit formulae of spectral norms for circulant-type matrices are investigated; the matrices are circulant matrix, skew-circulant matrix, and g-circulant matrix, respectively. The entries are products of binomial coefficients with harmonic numbers. Explicit identities for these spectral norms are obtained. Employing these approaches, some numerical tests are listed to verify the results.

  3. Effect of recombinant bovine granulocyte colony-stimulating factor covalently bound to polyethylene glycol injection on neutrophil number and function in periparturient dairy cows.

    Science.gov (United States)

    Kimura, Kayoko; Goff, Jesse P; Canning, Peter; Wang, Chong; Roth, James A

    2014-01-01

    Dairy cows often experience decreased immune function around the time of calving, typified by impaired polymorphonuclear neutrophil (PMN) function and a transient neutropenia. This is associated with increased disease incidence, including mastitis, retained placenta, and metritis. In an attempt to improve PMN functional capacity during the periparturient period, we injected cows with recombinant bovine granulocyte colony-stimulating factor covalently bound to polyethylene glycol (PEG rbG-CSF) twice subcutaneously, about 6d before calving and within 24h after calving. Twenty-one cows in their second pregnancy were enrolled in this study and divided into 2 groups: PEG rbG-CSF treated (n=11) and saline-treated controls (n=10). The PMN numbers quickly and dramatically increased after PEG rbG-CSF administration and remained elevated through the end of the experiment (13d after calving). Exocytosis of myeloperoxidase by stimulated PMN, which is generally decreased in periparturient cows, was markedly increased by PEG rbG-CSF after injection. Higher myeloperoxidase exocytosis persisted for at least 10d after calving. The PMN superoxide anion release and phagocytosis activity did not differ between groups. Injection of PEG rbG-CSF was safe for cows, with no significant negative effects observed. The greatest single effect of PEG rbG-CSF administration was a dramatic increase in circulating numbers of PMN. The increased numbers of PMN ready to move to a site of infection early in the course of an infection may improve the ability of the cow to ward off clinical disease in the periparturient period. PMID:24881799

  4. High-Reynolds Number Circulation Control Testing in the National Transonic Facility

    Science.gov (United States)

    Milholen, William E., II; Jones, Gregory S.; Chan, David T.; Goodliff, Scott L.

    2012-01-01

    A new capability to test active flow control concepts and propulsion simulations at high Reynolds numbers in the National Transonic Facility at the NASA Langley Research Center is being developed. The first active flow control experiment was completed using the new FAST-MAC semi-span model to study Reynolds number scaling effects for several circulation control concepts. Testing was conducted over a wide range of Mach numbers, up to chord Reynolds numbers of 30 million. The model was equipped with four onboard flow control valves allowing independent control of the circulation control plenums, which were directed over a 15% chord simple-hinged flap. Preliminary analysis of the uncorrected lift data showed that the circulation control increased the low-speed maximum lift coefficient by 33%. At transonic speeds, the circulation control was capable of positively altering the shockwave pattern on the upper wing surface and reducing flow separation. Furthermore, application of the technique to only the outboard portion of the wing demonstrated the feasibility of a pneumatic based roll control capability.

  5. Invertibility and Explicit Inverses of Circulant-Type Matrices with k-Fibonacci and k-Lucas Numbers

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    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices have important applications in solving ordinary differential equations. In this paper, we consider circulant-type matrices with the k-Fibonacci and k-Lucas numbers. We discuss the invertibility of these circulant matrices and present the explicit determinant and inverse matrix by constructing the transformation matrices, which generalizes the results in Shen et al. (2011.

  6. Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal.

    Science.gov (United States)

    Singel, Kelly L; Segal, Brahm H

    2016-09-01

    Neutrophils are the first responders to infection and injury and are critical for antimicrobial host defense. Through the generation of reactive oxidants, activation of granular constituents and neutrophil extracellular traps, neutrophils target microbes and prevent their dissemination. While these pathways are beneficial in the context of trauma and infection, their off-target effects in the context of tumor are variable. Tumor-derived factors have been shown to reprogram the marrow, skewing toward the expansion of myelopoiesis. This can result in stimulation of both neutrophilic leukocytosis and the release of immature granulocytic populations that accumulate in circulation and in the tumor microenvironment. While activated neutrophils have been shown to kill tumor cells, there is growing evidence for neutrophil activation driving tumor progression and metastasis through a number of pathways, including stimulation of thrombosis and angiogenesis, stromal remodeling, and impairment of T cell-dependent anti-tumor immunity. There is also growing appreciation of neutrophil heterogeneity in cancer, with distinct neutrophil populations promoting cancer control or progression. In addition to the effects of tumor on neutrophil responses, anti-neoplastic treatment, including surgery, chemotherapy, and growth factors, can influence neutrophil responses. Future directions for research are expected to result in more mechanistic knowledge of neutrophil biology in the tumor microenvironment that may be exploited as prognostic biomarkers and therapeutic targets. PMID:27558344

  7. Immunosenescence of Polymorphonuclear Neutrophils

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    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.

  8. Optimal number of circulating water pumps in a nuclear power plant

    International Nuclear Information System (INIS)

    Highlights: • We present a novel method to optimize the number of variable speed pumps. • The economic effect of variable speed pumps number optimization is presented. • We present a novel method to optimize the number of constant speed pumps. • The proposed pumps number optimization method is more accurate than the widely used method. - Abstract: A circulating cooling system that uses variable speed pumps (VSPs) or constant-speed pumps (CSPs) as circulating water pumps (CWPs) is optimized to improve the cycle efficiency of nuclear power plants. This study focused on the optimal number of VSPs and CSPs. A novel method is proposed to optimize the number of VSPs with varying dry-bulb temperature and relative humidity, which could help decrease operation costs by $243,310 per year. This method is also used to optimize the number of CSPs and is compared with another widely used method that optimizes the number of CSPs according to the varying condenser inlet water temperature. A comparison shows that the proposed method is more accurate than the widely used method

  9. Optimal number of circulating water pumps in a nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Lin [College of Water Conservancy and Hydropower Engineering, Hohai University, Nanjing 210098, Jiangsu (China); Liu, Deyou, E-mail: liudyhhuc@163.com [College of Water Conservancy and Hydropower Engineering, Hohai University, Nanjing 210098, Jiangsu (China); Zhou, Ling, E-mail: zlhhu@163.com [College of Water Conservancy and Hydropower Engineering, Hohai University, Nanjing 210098, Jiangsu (China); Wang, Feng [School of Hydraulic, Energy and Power Engineering, Yangzhou University, Yangzhou 225009, Jiangsu (China); Wang, Pei [College of Energy and Electrical Engineering, Hohai University, Nanjing 210098, Jiangsu (China)

    2015-07-15

    Highlights: • We present a novel method to optimize the number of variable speed pumps. • The economic effect of variable speed pumps number optimization is presented. • We present a novel method to optimize the number of constant speed pumps. • The proposed pumps number optimization method is more accurate than the widely used method. - Abstract: A circulating cooling system that uses variable speed pumps (VSPs) or constant-speed pumps (CSPs) as circulating water pumps (CWPs) is optimized to improve the cycle efficiency of nuclear power plants. This study focused on the optimal number of VSPs and CSPs. A novel method is proposed to optimize the number of VSPs with varying dry-bulb temperature and relative humidity, which could help decrease operation costs by $243,310 per year. This method is also used to optimize the number of CSPs and is compared with another widely used method that optimizes the number of CSPs according to the varying condenser inlet water temperature. A comparison shows that the proposed method is more accurate than the widely used method.

  10. On the Determinants and Inverses of Circulant Matrices with Pell and Pell-Lucas Numbers

    CERN Document Server

    Bozkurt, Durmuş

    2012-01-01

    Let P=\\circ(P_{1},P_{2},...,P_{n}) and Q=\\circ(Q_{1},Q_{2},...,Q_{n}) be n\\timesn circulant matrices where P_{n} and Q_{n} are nth Pell and Pell-Lucas numbers, respectively. The determinants of the matrices P and Q were expressed by the Pell and Pell-Lucas numbers. After, we prove that the matrices P and Q are the invertible for n\\geq3 and then the inverses of the matrices P and Q are derived.

  11. Vortices with half-integer number of circulation quanta in superfluid 3He-A

    International Nuclear Information System (INIS)

    A method is proposed for the experimental observation of the exotic vortices with a half-integer number of superfluid velocity circulation quanta in rotating 3He-A. The existence of such vortices in 3He-A is possible due to the presence of discrete combined symmetry (gauge transformation+spin rotation). This symmetry couples in a nontrivial manner the superfluid and magnetic properties of the liquid and gives rise to the hybrid of the vortex and disclination in the field of the magnetic anisotropy vector. In a free geometry such vortices are energetically not advantageous due to the spin-orbit (dipole) energy since they are termination lines of the topological solitons. For a parallel-plane geometry with distances between the planes which are smaller than the dipole lenght and in the presence of a sufficiently strong magnetic field normal to the plates the dipole energy is neutralized, and the vortices with half-integer circulation may compete successfully with other types of vortices. Vortices with a half-integer number of quanta should lead to a characteristic behaviour of the NMR signal, and on this basis they may distinguished from singular vortices with a single circulation quantum and from nonsingular vortices with two quanta

  12. The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization

    OpenAIRE

    Wu, Mike C. L.; Brennan, Faith H; Lynch, Jason P. L.; Mantovani, Susanna; Phipps, Simon; Wetsel, Rick A.; Ruitenberg, Marc J.; Taylor, Stephen M.; Woodruff, Trent M.

    2013-01-01

    C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used a neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role of C3aR in acute tissue injuries. C3aR deficiency worsened intestinal injury, which corresponded with increased numbers of tissue-infiltrating neutrophils. Circulating neutrophils were significantly increased in C3aR−/− mice after intestinal ische...

  13. AUTOANTIBODY LEVELS INFLUENCES THE NUMBER AND PHENOTYPE OF INFILTRATING NEUTROPHILS IN INFLAMED JOINTS OF PATIENTS WITH RHEUMATOID ARTHRITIS

    OpenAIRE

    Rodrigo Fernando Blas; Alicia Munarriz; Hector Tamashiro; Rodolfo A Pardo Hidalgo; Maria Cristina Pistoresi-Palencia; Maria Silvia Di Genaro

    2015-01-01

    Rheumatoid arthritis (RA) manifests with persistent synovial inflammation, cellular infiltration and pro-inflammatory cytokine production, and results in progressive joint destruction. Although the etiology and pathogenesis of RA are still unclear, there are many inflammatory cells accumulated in the synovial fluid (SF) which are involved in the pathogenesis of RA. Of all the cell types implicated in the pathology of RA, neutrophils are the most abundant cells present either in the SF of the ...

  14. Kinematic vorticity number – a tool for estimating vortex sizes and circulations

    Directory of Open Access Journals (Sweden)

    Lisa Schielicke

    2016-02-01

    Full Text Available The influence of extratropical vortices on a global scale is mainly characterised by their size and by the magnitude of their circulation. However, the determination of these properties is still a great challenge since a vortex has no clear delimitations but is part of the flow field itself. In this work, we introduce a kinematic vortex size determination method based on the kinematic vorticity number Wk to atmospheric flows. Wk relates the local rate-of-rotation to the local rate-of-deformation at every point in the field and a vortex core is identified as a simply connected region where the rotation prevails over the deformation. Additionally, considering the sign of vorticity in the extended Wk-method allows to identify highs and lows in different vertical layers of the atmosphere and to study vertical as well as horizontal vortex interactions. We will test the Wk-method in different idealised -D (superposition of two lows/low and jet and real -D flow situations (winter storm affecting Europe and compare the results with traditional methods based on the pressure and the vorticity fields. In comparison to these traditional methods, the Wk-method is able to extract vortex core sizes even in shear-dominated regions that occur frequently in the upper troposphere. Furthermore, statistics of the size and circulation distributions of cyclones will be given. Since the Wk-method identifies vortex cores, the identified radii are subsynoptic with a broad peak around 300–500 km at the 1000 hPa level. However, the total circulating area is not only restricted to the core. In general, circulations are in the order of 107 m2/s with only a few cyclones in the order of 108 m2/s.

  15. Kinematic vorticity number – a tool for estimating vortex sizes and circulations

    OpenAIRE

    Schielicke, Lisa; Névir, Peter; Ulbrich, Uwe

    2016-01-01

    The influence of extratropical vortices on a global scale is mainly characterised by their size and by the magnitude of their circulation. However, the determination of these properties is still a great challenge since a vortex has no clear delimitations but is part of the flow field itself. In this work, we introduce a kinematic vortex size determination method based on the kinematic vorticity number Wk to atmospheric flows. Wk relates the local rate-of-rotation to the local rate-of-deformat...

  16. Changes in the number of circulating CD34+cells after eccentric exercise of the elbow flexors in relation to muscle damage

    Institute of Scientific and Technical Information of China (English)

    Ho Seong Lee; Makii Muthalib; Takayuki Akimoto; Kazunori Nosaka

    2015-01-01

    Background:It has been reported that strenuous exercise increases the number of bone marrow-derived progenitor cells such as CD34+cells in the blood, but no previous studies have investigated the changes in circulating CD34+cells following resistance exercise. This study tested the hypothesis that the number of CD34+cells in the blood would increase after eccentric exercise of the elbow flexors, but decrease in recovery, and the magnitude of the changes would be dependent on the magnitude of muscle damage. Methods:Nine men (28.0 ± 6.6 years) performed exercises consisting of 10 sets of six maximal voluntary eccentric contractions of the elbow flexors with their non-dominant arm. Six of them performed the same exercise with the same arm 4 weeks later. Changes in indirect markers of muscle damage were measured before, within 10 min after, and at 24, 48, 72, and 96 h after eccentric exercise. Differential leukocyte counts (total leukocytes, neutrophils, lymphocytes, monocytes) and CD34+cells in the blood were measured before, immediately after, and at 2, 24, 48, 72, and 96 h following the exercises. Results:After eccentric exercise, significant ( p<0.05) decreases in maximal voluntary isometric contraction torque and increases in delayed onset muscle soreness and plasma creatine kinase activity were observed. However, no significant changes in leukocytes and CD34+cells were evident. The changes in muscle damage markers were significantly ( p<0.05) smaller following the second exercise session as compared with the first exercise session, but the changes in leukocytes and CD34+cells were not significantly different between sessions. Conclusion:These results did not support the hypothesis, and showed that eccentric exercise-induced muscle damage to the elbow flexors did not influence the number of circulating CD34+cells.

  17. Aging: A Temporal Dimension for Neutrophils.

    Science.gov (United States)

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

    2016-05-01

    Neutrophils are first-responders, providing early protection against invading pathogens. Recent findings have revealed a temporal dimension to neutrophil function, associated with the clearance cycles for aging neutrophils, and also with a program that endows circulating neutrophils with distinct phenotypic and functional properties at different times of the day, before they are cleared from blood. We review here the process of neutrophil aging and its impact on homeostasis and inflammation. We outline the features of aged neutrophils, examine proposed mechanisms that drive aging, and discuss how these processes may contribute to tissue homeostasis and pathology. In this context we propose that neutrophil aging may optimize host defense by allowing neutrophils to anticipate infections while avoiding permanent activation and subsequent damage. PMID:27083489

  18. The effects of phototherapy on the numbers of circulating natural killer cells and T lymphocytes in psoriasis.

    LENUS (Irish Health Repository)

    Tobin, A M

    2009-04-01

    The innate immune system is believed to be important in the pathogenesis of psoriasis and natural killer (NK) have been found in increased numbers in psoriatic plaques. Alterations in the numbers of NK cells in peripheral blood have been reported. We investigated the effect of phototherapy on levels of peripheral NK cells and lymphocytes in patients with psoriasis. In nine patients whom we followed before, during and after narrowband ultraviolet B (UVB) treatment there were no differences in the numbers of circulating lymphocytes, lymphocyte subsets or cells expressing NK markers and controls. Treatment with narrowband UVB did, however, significantly lower circulating CD4 counts which gradually recovered posttreatment.

  19. Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury.

    Science.gov (United States)

    Wu, Deqing; Zeng, Yue; Fan, Yuting; Wu, Jianghong; Mulatibieke, Tunike; Ni, Jianbo; Yu, Ge; Wan, Rong; Wang, Xingpeng; Hu, Guoyong

    2016-01-01

    Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM. PMID:26841848

  20. Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat.

    Directory of Open Access Journals (Sweden)

    Jean F Regal

    Full Text Available Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN antibody (antiPMN. Rats received either antiPMN or normal rabbit serum (Control on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc. On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP. On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension.

  1. Determinants of the RFMLR Circulant Matrices with Perrin, Padovan, Tribonacci, and the Generalized Lucas Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available The row first-minus-last right (RFMLR circulant matrix and row last-minus-first left (RLMFL circulant matrices are two special pattern matrices. By using the inverse factorization of polynomial, we give the exact formulae of determinants of the two pattern matrices involving Perrin, Padovan, Tribonacci, and the generalized Lucas sequences in terms of finite many terms of these sequences.

  2. Adiponectin levels are associated with the number and activity of circulating endothelial progenitor cells in patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang YING; Dan-dan ZHONG; Geng XU; Miao-yan CHEN; Qing-yu CHEN

    2009-01-01

    Objective: To study the relationship between plasma adiponectin concentration and the functional activities of circulating endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). Methods: Circulating EPCs were enumerated as AC133+/KDR+ cells via flow cytometry and identified by co-staining with Dii-acLDL and fluorescein isothiocy-anate (FITC)-conjugated lectin under a fluorescent microscope. The migratory capacity of EPCs was measured by modified Boyden chamber assay. Adhesion capacity was performed to count adherent cells after replating EPCs on six-well culture dishes coated with fibronectin. Results: The number of circulating EPCs (AC133+/KDR+ cells) decreased significantly in CAD patients, compared with control subjects [(74.2±12.3) vs (83.5±12.9) cells/ml blood, P<0.0\\]. In addition, the number of EPCs also decreased in CAD patients after ex vivo cultivation [(54.4±8.6) vs (71.9±11.6) EPCs/field, P<0.01]. Both circulating EPCs and differentiated EPCs were positively correlated with plasma adiponectin concentration. The functional activities of EPCs from CAD patients, such as migratory and adherent capacities, were also impaired, compared with control subjects, and positively correlated with plasma adiponectin concentration. Conclusion: The study demonstrates that the impairment of the number and functional activities of EPCs in CAD patients is correlated with their lower plasma adiponectin concentrations.

  3. Low Number of Detectable Circulating Tumor Cells in Non-metastatic Colon Cancer

    DEFF Research Database (Denmark)

    Thorsteinsson, Morten; Söletormos, György; Jess, Per

    2011-01-01

    The aim of the present study was to detect circulating tumor cells (CTCs) in the peripheral blood of patients with non-metastatic colon cancer and to evaluate whether there is a diurnal variation in the CTC counts. Furthermore, the study aimed to examine the correlation between CTCs and TNM stage...

  4. Neutrophil Homeostasis and Periodontal Health in Children and Adults

    OpenAIRE

    Hajishengallis, E.; Hajishengallis, G

    2014-01-01

    This review summarizes the current state of knowledge on neutrophil basic biology and discusses how the breakdown of neutrophil homeostasis affects periodontal health. The homeostasis of neutrophils is tightly regulated through coordinated bone marrow production, release into the circulation, transmigration to and activation in peripheral tissues, and clearance of senescent neutrophils. Dysregulation of any of these homeostatic mechanisms at any age can cause severe periodontitis in humans an...

  5. Asymptotic enumeration theorems for the numbers of spanning trees and Eulerian trails in circulant digraphs and graphs

    Institute of Scientific and Technical Information of China (English)

    张福基; 永学荣

    1999-01-01

    The asymptotic properties of the numbers of spanning trees and Eulerian trails in circulant digraphs and graphs are studied. Let C(p, s1, s2,…, sk) be a directed cireulant graph. Let T(C(p, s1, s2, …, sk)) and E(C(p, s1, s2, …, sk)) be the numbers of spanning trees and of Eulerian trails, respectively. Then lim (1/k)(T(C(p, s1, S2, …, sk))1/p)=1, p→∞ lim (1/k!)(E(C(p, s1, s2, …, sk))1/p)=1,Furthermore, their line digraph and iterations are dealt with and similar results are obtained for undirected circulant graphs.

  6. Dendritic Cell Protection from Cisplatin Nephrotoxicity Is Independent of Neutrophils

    Directory of Open Access Journals (Sweden)

    Raghu K. Tadagavadi

    2015-08-01

    Full Text Available Cisplatin is a very effective chemotherapeutic agent used against a wide range of solid tumors. A major adverse effect of cisplatin therapy is acute kidney injury (AKI. Neutrophils are reported to infiltrate and exacerbate injury in a wide range of sterile inflammatory models of tissue injury. Here, we studied the kinetics of neutrophil infiltration into kidneys and their role in cisplatin-mediated AKI. Mice treated with cisplatin showed an increase in circulating neutrophils 24 and 48 h after cisplatin administration. Cisplatin treatment caused an increase in kidney leukocytes with neutrophils accounting for the majority of the infiltrating leukocytes. The extent of neutrophil infiltration coincided with the severity of kidney injury and renal dysfunction. To examine the functional relevance of infiltrating neutrophils in cisplatin nephrotoxicity, we depleted neutrophils using a neutrophil-specific antibody (anti-Ly-6G. This antibody resulted in greater than 90% depletion of neutrophils in both the blood and kidney. Of note, depletion of neutrophils had no impact on the extent of cisplatin-induced AKI as compared to non-depleted mice. Earlier, we reported that dendritic cell depletion in CD11c-DTRtg mice causes exacerbation of AKI and a dramatic increase in renal neutrophils. Thus, we also examined the role of neutrophils in dendritic cell-depleted mice treated with cisplatin. Dendritic cell depletion exacerbated AKI in spite of neutrophil depletion. These data demonstrate that cisplatin nephrotoxicity is not mediated by neutrophils and that dendritic cells protect kidneys via neutrophil-independent mechanisms.

  7. Annual FEV1 changes and numbers of circulating endothelial microparticles in patients with COPD: a prospective study

    OpenAIRE

    Takahashi, Toru; Kobayashi, Seiichi; Fujino, Naoya; Suzuki, Takaya; Ota, Chiharu; Tando, Yukiko; Yamada, Mitsuhiro; Yanai, Masaru; Yamaya, Mutsuo; Kurosawa, Shin; Yamauchi, Masanori; Kubo, Hiroshi

    2014-01-01

    Objective Growing evidence suggests that endothelial injury is involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). Circulating endothelial microparticles (EMPs) increase in patients with COPD because of the presence of endothelial injury. We examined the relationship between EMP number and changes in forced expiratory volume in 1 s (FEV1) in patients with COPD. Design Prospective study. Setting One hospital in Japan. Participants A total 48 outpatients with stable...

  8. Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Ju-Yu [Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan (China); Yang, Chih-Yung [Department of Education and Research, Taipei City Hospital, Taipei 10629, Taiwan (China); Liang, Shu-Ching [Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan (China); Liu, Ren-Shyan [Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, Taipei 11529, Taiwan (China); Biomedical Imaging Research Center, Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China); National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan (China); Jiang, Jeng-Kai, E-mail: jkjiang@vghtpe.gov.tw [Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan (China); Lin, Chi-Hung, E-mail: jkjiang@vghtpe.gov.tw [Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan (China); VGH Yang-Ming Genome Research Center, Taipei 11221, Taiwan (China)

    2014-12-16

    Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis.

  9. Dynamic changes in numbers and properties of circulating tumor cells and their potential applications.

    Science.gov (United States)

    Tseng, Ju-Yu; Yang, Chih-Yung; Liang, Shu-Ching; Liu, Ren-Shyan; Jiang, Jeng-Kai; Lin, Chi-Hung

    2014-01-01

    Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a "real-time biopsy" and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis. PMID:25521853

  10. Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications

    International Nuclear Information System (INIS)

    Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis

  11. The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64.

    Science.gov (United States)

    McCarthy, Desmond A; Macey, Marion G; Streetly, Matthew; Schey, Stephen A; Brown, K Alun

    2006-07-01

    A major limitation to the treatment of multiple myeloma by the thalidomide analogue CC-4047 (Actimid) is the development of a severe neutropenia. We investigated the hypothesis that this effect may have been due to CC-4047 enhancing the removal of neutrophils from the circulation by altering the expression of surface adhesion molecules required for endothelial binding, by binding to platelets, or by enhancing apoptosis. Flow cytometric analysis was used to examine the expression of neutrophil surface molecules, platelet binding and apoptosis in whole blood samples from 19 patients with multiple myeloma who were assigned to receive either 1, 2, 5 or 10 mg of CC-4047 every other day (e.o.d.) for 28 days. CC-4047 induced dose-related decreases in neutrophil numbers and increases in the percentage of CD64-positive neutrophils, but had little, or no effect on the expression of CD11b, CD62L or CD162, neutrophil-platelet binding, or apoptosis. Relative decreases in the neutrophil count were inversely associated with relative increases in the intensity of CD64 expression on neutrophils (r=- 0.307; p=0.028). Although seven patients developed severe neutropenia, none suffered severe or recurrent bacterial infections. The percentage of CD64-positive neutrophils was still increased in eight patients who continued receiving 1-5 mg CC-4047 e.o.d. for several months afterwards, but neutrophil counts were similar to pre-treatment values. PMID:16714224

  12. Circulating levels of matrix metalloproteinase-9 (MMP-9, neutrophil gelatinase-associated lipocalin (NGAL and their complex MMP-9/NGAL in breast cancer disease

    Directory of Open Access Journals (Sweden)

    Nonni Afroditi

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9 is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

  13. Heat transfer experiments and correlations for natural and forced circulations of water in rod bundles at low Reynolds numbers

    International Nuclear Information System (INIS)

    Experimental heat transfer studies were conducted for fully developed forced and natural flows of water through seven uniformly heated rod bundles, triangularly arrayed with P/D = 1.25, 1.38, and 1.5. In forced circulation experiments, Re ranged from 80 to 50,000 and Pr from 3 to 8.5, while in natural circulation, Re varied from 260 to 2,000, and Raq from 8 x 108 to 2.5 x 108. The forced flow data fell into the two basic flow regimes: turbulent and laminar flow. At the transition between these regimes, Re, which varied from 2,200 for P/D = 1.25 to 5,500 for P/D = 1.5, increased linearly with P/D. The heat transfer data for turbulent flow was within ±15 percent of Weisman's correlation, which was developed for fully developed turbulent flow in rod bundles at Re > 25,000. The laminar flow data showed the dependence of Nu on Re to be weaker than that for turbulent flow, but the exponent of Re increased with P/D: Nu = A ReB Pr1/3, where A is equal to 1.061, 0.511, and 0.346 for P/D = 1.25, 1.38 and 1.5, respectively, and B is a linear function of P/D (B = 0.797 P/D - 0.656). Natural circulation data indicated that rod spacing only slightly affected heat transfer, and Nu increased proportionally to Ra0.25; Nu = 0.272 Raq0.25. The application of the results to SNL's ACRR indicated that although the core is cooled by natural convection, either the natural circulation correlation or the forced turbulent flow correlation can be used to accurately predict the single phase heat transfer coefficient in the ACRR. These results were concluded because of the high Rayleigh and Reynolds numbers in the ACRR. The ACRR operates near the boundary between mixed and forced turbulent flow regimes: consequently, achieving the high heat transfer coefficient was possible with natural circulation. (author)

  14. Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production

    Directory of Open Access Journals (Sweden)

    Khazaei Majid

    2011-02-01

    Full Text Available Abstract Background Epidemiological studies propose that obesity increases the risk of several cancers, including melanoma. Obesity increases the expression of leptin, a multifunctional peptide produced predominantly by adipocytes which may promote tumor growth. Several recently experiments have suggested that the tumors growth is in need of endothelial progenitor cell (EPC dependent generation of new blood vessels. Our objectives in the present study were to examine the effects of leptin on melanoma growth, circulating EPCs number and plasma levels of nitric oxide metabolites (NOx. Methods 2 × 106 B16F10 melanoma cells were injected to thirty two C57BL6 mice subcutaneously. The mice were randomly divided into 4 groups (n = 8 in 8th day. Two groups were received twice daily intraperitoneal(i.p injections of either PBS or recombinant murine leptin (1 μg/g initial body weight. Two groups were received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 μg/mouse every 3 consecutive days. By the end of the second week the animals were euthanized and blood samples and tumors were analyzed. Results The tumor weight, EPC numbers and NOx level in leptin, PBS, 9F8, and IgG group were (3.2 ± 0.6, 1.7 ± 0.3, 1.61 ± 0.2,1.7 ± 0.3 g, (222.66 ± 36.5, 133.33 ± 171, 23.33 ± 18, 132.66 ± 27.26/ml of blood, and (22.47 ± 5.5, 12.30 ± 1.5, 6.26 ± 0.84, 15.75 ± 6.3 μmol/L respectively. Tumors weight and size, circulating EPC numbers and plasma levels of NOx were significantly more in the leptin than 9f8 and both control groups (p Conclusions In conclusion, our observations indicate that leptin causes melanoma growth likely through increased NO production and circulating EPC numbers and consequently vasculogenesis.

  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. 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 ...

  17. 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.

  18. N-Formyl peptides drive mitochondrial damage associated molecular pattern induced neutrophil activation through ERK1/2 and P38 MAP kinase signalling pathways.

    Science.gov (United States)

    Hazeldine, Jon; Hampson, Peter; Opoku, Francis Adusei; Foster, Mark; Lord, Janet M

    2015-01-01

    Traumatic injury results in a systemic inflammatory response syndrome (SIRS), a phenomenon characterised by the release of pro-inflammatory cytokines into the circulation and immune cell activation. Released from necrotic cells as a result of tissue damage, damage associated molecular patterns (DAMPs) are thought to initiate the SIRS response by activating circulating immune cells through surface expressed pathogen recognition receptors. Neutrophils, the most abundant leucocyte in human circulation, are heavily implicated in the initial immune response to traumatic injury and have been shown to elicit a robust functional response to DAMP stimulation. Here, we confirm that mitochondrial DAMPs (mtDAMPs) are potent activators of human neutrophils and show for the first time that signalling through the mitogen-activated-protein-kinases p38 and extracellular-signal-related-kinase 1/2 (ERK1/2) is essential for this response. At 40 and/or 100 μg/ml, mtDAMPs activated human neutrophils, indicated by a significant reduction in the surface expression of L-selectin, and triggered a number of functional responses from both resting and tumour necrosis factor-α primed neutrophils, which included reactive oxygen species (ROS) generation, degranulation, secretion of interleukin-8 and activation of p38 and ERK1/2 MAPKs. Pre-treatment of neutrophils with Cyclosporin H, a selective inhibitor of formyl peptide receptor-1 (FPR-1), significantly inhibited mtDAMP-induced L-selectin shedding as well as p38 and ERK1/2 activation, suggesting that N-formyl peptides are the main constituents driving mtDAMP-induced neutrophil activation. Indeed, no evidence of L-selectin shedding or p38 and ERK1/2 activation was observed in neutrophils challenged with mitochondrial DNA alone. Interestingly, pharmacological inhibition of p38 or ERK1/2 either alone or in combination significantly inhibited L-selectin shedding and IL-8 secretion by mtDAMP-challenged neutrophils, revealing for the first time

  19. Dimethylfumarate Impairs Neutrophil Functions.

    Science.gov (United States)

    Müller, Susen; Behnen, Martina; Bieber, Katja; Möller, Sonja; Hellberg, Lars; Witte, Mareike; Hänsel, Martin; Zillikens, Detlef; Solbach, Werner; Laskay, Tamás; Ludwig, Ralf J

    2016-01-01

    Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration. Phagocytic ability and autoantibody-induced, neutrophil-dependent tissue injury ex vivo was also impaired by DMF. Regarding the mode of action, DMF modulates-in a stimulus-dependent manner-neutrophil activation using the phosphoinositide 3-kinase/Akt-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways. For in vivo validation, mouse models of epidermolysis bullosa acquisita, an organ-specific autoimmune disease caused by autoantibodies to type VII collagen, were employed. In the presence of DMF, blistering induced by injection of anti-type VII collagen antibodies into mice was significantly impaired. DMF treatment of mice with clinically already-manifested epidermolysis bullosa acquisita led to disease improvement. Collectively, we demonstrate a profound inhibitory activity of DMF on neutrophil functions. These findings encourage wider use of DMF in patients with neutrophil-mediated diseases. PMID:26763431

  20. Dietary zinc oxide in weaned pigs--effects on performance, tissue concentrations, morphology, neutrophil functions and faecal microflora.

    Science.gov (United States)

    Jensen-Waern, M; Melin, L; Lindberg, R; Johannisson, A; Petersson, L; Wallgren, P

    1998-01-01

    The uptake and distribution of zinc in tissues and the effects of 2500 ppm dietary zinc oxide on health, faecal microflora, and the functions of circulating neutrophils were evaluated in weaned pigs. One group was fed a zinc supplement diet and another group was used as a control. All pigs remained healthy throughout the study, but the supplemented animals showed better performance than the controls. The serum zinc values rose rapidly. At autopsy, carried out at the age of 63 days, the zinc concentrations in liver tissue were 4.5 times higher, and in renal tissue two times higher in the supplemented group than in controls (Ppigs. No effect on the number of excreted Escherichia coli and enterococci per gram faeces or on the functions of circulating neutrophils was observed. Dietary supplementation with 2500 ppm ZnO for up to two weeks after weaning appears to be potentially beneficial in the prevention of postweaning diarrhoea in pigs. PMID:9690608

  1. Annexin A1 Is a Physiological Modulator of Neutrophil Maturation and Recirculation Acting on the CXCR4/CXCL12 Pathway.

    Science.gov (United States)

    Machado, Isabel Daufenback; Spatti, Marina; Hastreiter, Araceli; Santin, José Roberto; Fock, Ricardo Ambrósio; Gil, Cristiane Damas; Oliani, Sonia Maria; Perretti, Mauro; Farsky, Sandra Helena Poliselli

    2016-11-01

    Neutrophil production and traffic in the body compartments is finely controlled, and the strong evidences support the role of CXCL12/CXCR4 pathway on neutrophil trafficking to and from the bone marrow (BM). We recently showed that the glucocorticoid-regulated protein, Annexin A1 (AnxA1) modulates neutrophil homeostasis and here we address the effects of AnxA1 on steady-state neutrophil maturation and trafficking. For this purpose, AnxA1(-/-) and Balb/C wild-type mice (WT) were donors of BM granulocytes and mesenchymal stem cells and blood neutrophils. In vivo treatments with the pharmacological AnxA1 mimetic peptide (Ac2-26) or the formyl peptide receptor (FPR) antagonist (Boc-2) were used to elucidate the pathway of AnxA1 action, and with the cytosolic glucocorticoid antagonist receptor RU 38486. Accelerated maturation of BM granulocytes was detected in AnxA1(-/-) and Boc2-treated WT mice, and was reversed by treatment with Ac2-26 in AnxA1(-/-) mice. AnxA1 and FPR2 were constitutively expressed in bone marrow granulocytes, and their expressions were reduced by treatment with RU38486. Higher numbers of CXCR4(+) neutrophils were detected in the circulation of AnxA1(-/-) or Boc2-treated WT mice, and values were rescued in Ac2-26-treated AnxA1(-/-) mice. Although circulating neutrophils of AnxA1(-/-) animals were CXCR4(+) , they presented reduced CXCL12-induced chemotaxis. Moreover, levels of CXCL12 were reduced in the bone marrow perfusate and in the mesenchymal stem cell supernatant from AnxA1(-/-) mice, and in vivo and in vitro CXCL12 expression was re-established after Ac2-26 treatment. Collectively, these data highlight AnxA1 as a novel determinant of neutrophil maturation and the mechanisms behind blood neutrophil homing to BM via the CXCL12/CXCR4 pathway. J. Cell. Physiol. 231: 2418-2427, 2016. © 2016 Wiley Periodicals, Inc. PMID:26892496

  2. Alteration of neutrophil function in BCG-treated and non-treated swine after exposure to Salmonella typhimurium.

    Science.gov (United States)

    Coe, N E; Frank, D E; Wood, R L; Roth, J A

    1992-06-01

    Salmonella typhimurium infection in swine causes an enterocolitis followed by a persistent carrier state, but little is known about the mechanisms that allow this organism to colonize and persist in host tissues. Neutrophils provide a first line of defense against invading pathogens such as Salmonella typhimurium. The purpose of this study was to evaluate porcine neutrophil function after in vivo exposure to Salmonella and to determine if the immunomodulator, bacillus Calmette Guerin (BCG), exerts any effect on neutrophil function or on the colonization and persistence of S. typhimurium in the pig. Compared to negative controls, neutrophils from pigs exposed to S. typhimurium exhibited significantly decreased iodination, cytochrome-C reduction, antibody-dependent cell-mediated cytotoxicity, random migration, and chemotaxis (P less than or equal to 0.05). Neutrophil bactericidal activity against S. typhimurium was significantly enhanced. Most of the significant differences were noted in the first two days after exposure to Salmonella. Often the functional alterations were biphasic, peaking again 7-10 days after exposure. BCG alone significantly depressed random migration and cytochrome-C reduction in unstimulated neutrophils. The clinical course, colonization pattern, and persistence of Salmonella were similar between pigs receiving BCG and untreated pigs. These data suggest that S. typhimurium infection causes a depression in oxidative metabolism and motility, yet an increase in overall bactericidal activity against S. typhimurium in circulating porcine neutrophils. It also appears that BCG treatment, as reported here, does not enhance resistance of pigs to S. typhimurium colonization or reduce the number of persistent organisms in the porcine ileum. PMID:1321531

  3. Activation of Neutrophils by Nanoparticles

    Directory of Open Access Journals (Sweden)

    David M. Goncalves

    2011-01-01

    Full Text Available The use of nanoparticles (NPs has increased in the past few years in various fields, including defence, aerospace, electronics, biology, medicine, and so forth. and in applications such as diagnostic technology, bioimaging, and drug/gene delivery. Thus, human exposure to NPs and nanomaterials is unavoidable and will certainly expand in the future resulting in a growing interest in nanotoxicology, the study of toxicity of nanomaterials. A number of studies have reported the effects of NPs in respect to pulmonary inflammation by investigating in vitro activation of pulmonary cells with NPs and in vivo in a variety of models in which neutrophils appear to be the predominant leukocyte cell type in lungs and in bronchoalveolar lavages following inhalation or intratracheal instillation of NPs. Despite the fact that several studies have reported an increased number of neutrophils, the literature dealing with the direct activation of neutrophils by a given NP is poorly documented. This paper will summarize the current literature in this latter area of research and will end with a perspective view in which our laboratory will be involved in the following years.

  4. The alteration in peripheral neutrophils of patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Yevgenyevna Muravlyova Larissa

    2015-03-01

    Full Text Available Recent findings have demonstrated the impaired functions of neutrophils of patients with chronic renal failure. The purpose of our research was to study oxidative modified proteins, as well as the histone spectrum in neutrophils drawn from patients with chronic kidney disease, and to estimate the ability of neutrophils to form spontaneous neutrophil extracellular traps. In this work, we have assumed that metabolic alteration in neutrophils may develop at early stages of chronic kidney disease. Materials and methods: Neutrophils obtained from patients with various stages of chronic kidney disease and degrees of chronic renal failure were used. As control, blood samples obtained from 32 healthy individuals was employed. In the examined neutrophils, advanced oxidation protein products, protein reactive carbonyl derivatives, as well as nucleosomal histones were detected. The ability of neutrophils to form spontaneous neutrophil extracellular traps was estimated. Our results have demonstrated an increase of nucleosomal histones in neutrophils of all patients with chronic kidney disease. Moreover, our work fixes the rate of growth of intracellular advanced oxidation protein products and the decreasing of protein reactive carbonyl derivatives in neutrophils from patients with chronic kidney disease. Furthermore, we demonstrate the presence of the neutrophils with altered oxidative status and the decomposition of the histone spectrum in the circulation of patients with chronic kidney disease.

  5. Neutrophils in cystic fibrosis.

    Science.gov (United States)

    Laval, Julie; Ralhan, Anjali; Hartl, Dominik

    2016-06-01

    Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. Among inflammatory cells, neutrophils represent the major cell population accumulating in the airways of CF patients. While neutrophils provide the first defensive cellular shield against bacterial and fungal pathogens, in chronic disease conditions such as CF these short-lived immune cells release their toxic granule contents that cause tissue remodeling and irreversible structural damage to the host. A variety of human and murine studies have analyzed neutrophils and their products in the context of CF, yet their precise functional role and therapeutic potential remain controversial and incompletely understood. Here, we summarize the current evidence in this field to shed light on the complex and multi-faceted role of neutrophils in CF lung disease. PMID:26854289

  6. Subcellular Fractionation of Human Neutrophils and Analysis of Subcellular Markers

    DEFF Research Database (Denmark)

    Clemmensen, Stine Novrup; Udby, Lene; Borregaard, Niels

    2014-01-01

    The neutrophil has long been recognized for its impressive number of cytoplasmic granules that harbor proteins indispensable for innate immunity. Analysis of isolated granules has provided important information on how the neutrophil grades its response to match the challenges it meets on its pass...

  7. A morphologic study of the influx of neutrophils into dog lung alveoli after lavage with sterile saline.

    OpenAIRE

    Damiano, V. V.; Cohen, A; Tsang, A. L.; Batra, G.; Petersen, R

    1980-01-01

    The appearance of neutrophils in the alveoli of the lung is a common result of pulmonary infection, although the route of neutrophil migration across the alveolar wall has not been demonstrated in normal animals. Recently, however, several methods of stimulating the influx of neutrophils into alveoli have been developed. In the present study, the lung wash model was used to attract large numbers of neutrophils into the airways in order to identify the site of influx of alveolar neutrophils. T...

  8. LES of High-Reynolds-Number Coanda Flow Separating from a Rounded Trailing Edge of a Circulation Control Airfoil

    Science.gov (United States)

    Nichino, Takafumi; Hahn, Seonghyeon; Shariff, Karim

    2010-01-01

    This slide presentation reviews the Large Eddy Simulation of a high reynolds number Coanda flow that is separated from a round trailing edge of a ciruclation control airfoil. The objectives of the study are: (1) To investigate detailed physics (flow structures and statistics) of the fully turbulent Coanda jet applied to a CC airfoil, by using LES (2) To compare LES and RANS results to figure out how to improve the performance of existing RANS models for this type of flow.

  9. Proteinase 3 contributes to transendothelial migration of NB1-positive neutrophils

    OpenAIRE

    Kuckleburg, Christopher J.; Tilkens, Sarah M.; Santoso, Sentot; Newman, Peter J.

    2012-01-01

    Neutrophil transmigration requires the localization of neutrophils to endothelial cell junctions, where receptor-ligand interactions and the action of serine proteases promote leukocyte diapedesis. NB1 (CD177) is a neutrophil-expressed surface molecule that has been reported to bind proteinase 3 (PR3), a serine protease released from activated neutrophils. PR3 has demonstrated proteolytic activity on a number of substrates, including extracellular matrix proteins, although its role in neutrop...

  10. Neutrophilic alveolitis in Sweet's syndrome.

    OpenAIRE

    Bourke, S J; Quinn, A. G.; Farr, P M; Ashcroft, T.; Gibson, G. J.

    1992-01-01

    In a case of Sweet's syndrome (acute febrile neutrophilic dermatosis) neutrophilic alveolitis was found by lung biopsy. Pulmonary disease in this condition may be underrecognised yet, like the dermatological features, it responds rapidly to corticosteroids.

  11. Platelets enhance neutrophil transendothelial migration

    Science.gov (United States)

    Platelets are increasingly recognized as important mediators of inflammation in addition to thrombosis. While platelets have been shown to promote neutrophil (PMN) adhesion to endothelium in various inflammatory models, it is unclear whether platelets enhance neutrophil transmigration across inflame...

  12. Determination of vascular endothelial growth factor (VEGF) in circulating blood: significance of VEGF in various leucocytes and platelets

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2002-01-01

    contained considerable amounts of VEGF. In isolated lymphocytes and monocytes, VEGF was not present in measurable amounts. The number of neutrophils was significantly (p<0.0001) correlated to VEGF concentrations in lysed whole blood, but not to VEGF concentrations in plasma or serum. The number of platelets...... clotting. CONCLUSION: Circulating neutrophils contain considerable amounts of VEGF that contribute to high VEGF levels in lysed whole blood. VEGF in circulating platelets contributes to high VEGF levels in serum and lysed whole blood. Allowing whole blood samples to clot for between 2 and 6 h before serum......AIM: The sources of increased vascular endothelial growth factor (VEGF) concentrations in peripheral blood from cancer patients are not known in detail. The aim of the present study was to evaluate correlations between the VEGF content in isolated leucocyte subpopulations and VEGF concentrations in...

  13. Proteases of neutrophilic granulocytes

    OpenAIRE

    Wiesława Roszkowska-Jakimiec; Anna Worowska; Marek Gacko; Tomasz Maksimowicz

    2002-01-01

    The literature referring to proteolytic enzymes of neutrophilic granulocytes was surveyed. Biosynthesis, subcellular distribution, division according to the catalytic site structure, inhibitors and methods used to determine the activity of these enzymes were discussed. The survey included metaloproteases (granulocytic collagenase, gelatinase B), serine proteases (granulocytic elastase, cathepsin G, protease 3), membraneous proteases (aminopeptidase N, aminopeptidase P, neprilisine), cysteine ...

  14. [Leukemic neutrophilic dermatosis].

    Science.gov (United States)

    Török, L; Kirschner, A; Gurzó, M; Krenács, L

    1999-03-28

    A case of a 67 year-old female patient with acute myeloid leukemia is presented. As the first manifestation of the disease, the patient had symptoms of Sweet's syndrome, later signs of gangrenous pyoderma have developed. This transient form is termed as a "leukemic neutrophilic dermatosis". The authors focus on the important diagnostic and prognostic value of this entity. PMID:10349319

  15. Dual effect of neutrophils on secretory component production by human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    C. Pilette

    2006-12-01

    Full Text Available A decreased bronchial expression of secretory component (SC was demonstrated in severe COPD, and correlated with neutrophils. Mechanisms of epithelial cell/neutrophils interactions remain however poorly understood. Calu-3 (human bronchial epithelial cells were incubated after confluence (in triplicate conditions with various ratios of activated neutrophils (0.5:1 to 15:1, neutrophils: Calu-3 cells. After 48hrs of co-culture supernatants were assayed for SC by ELISA. SC production by Calu-3 cells increased at intermediate neutrophil numbers (316±32 versus 193±19ng·ml–1, ratio of 5:1 versus control, mean±SEM of 3 experiments, p = 0.05. In contrast, a trend for decrease in SC was observed with high neutrophil numbers (111±19 versus 193±19ng·ml–1, ratio of 15:1 versus control, p = 0.06. The addition of secretory leukocyte protease inhibitor further increased SC upregulation at intermediate ratios, and inhibited the SC decrease at high neutrophil numbers. The mechanism of SC up-regulation by neutrophils did not implicate TNF-alpha or IL-1beta. This study provides direct evidence of a dual effect of neutrophils on epithelial SC. Our data suggest that neutrophils could differently affect epithelial immune secretory function according to the extent of neutrophil influx and/or to the reactivity of airway epithelial cells.

  16. Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis

    OpenAIRE

    Alves-Filho, Jose C.; Freitas, Andressa; Souto, Fabricio O.; Spiller, Fernando; Paula-Neto, Heitor; Silva, Joao S.; Gazzinelli, Ricardo T.; Teixeira, Mauro M.; Ferreira, Sergio H.; Cunha, Fernando Q.

    2009-01-01

    Patients with sepsis have a marked defect in neutrophil migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of neutrophil migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired migration into an infectious focus in vivo. TLR2 deficiency ...

  17. A Wind Tunnel Experiment for Trailing Edge Circulation Control on a 6 Percent 2-D Airfoil up to Transonic Mach Numbers

    Science.gov (United States)

    Alexander, Michael G.; Anders, Scott G.; Johnson, Stuart K.

    2005-01-01

    A wind tunnel test was conducted on a six percent thick slightly cambered elliptical circulation control airfoil with both upper and lower surface blowing. Parametric evaluations of jet slot heights and Coanda surface shapes were conducted at mass flow coefficients (C(sub mu)) from 0.0 to 0.12. The test data was acquired in the NASA Langley Transonic Dynamics Tunnel at Mach numbers of 0.8 and 0.3 at Reynolds numbers per foot of 1.05 x 10(exp 6) and 2.43 x 10(exp 5) respectively. For the transonic condition, (Mach = 0.8 at alpha = +3 deg), it was generally found that the smaller slot and larger Coanda surface were more effective overall than other slot/Coanda surface combinations. Generally it was found at Mach = 0.3 at alpha = 6 deg that the smaller slot and smaller Coanda surface were more effective overall than other slot/Coanda surface combinations.

  18. Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis

    DEFF Research Database (Denmark)

    Clemmensen, Stine N; Jacobsen, Lars C; Rørvig, Sara;

    2011-01-01

    stimulation. A1AT is produced at all stages of myeloid maturation in the bone marrow. The production increases as neutrophils enter circulation and increases further upon migration to tissues as observed in skin windows and when blood neutrophils are incubated with granulocyte colony-stimulating factor......Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT is expressed by human neutrophil granulocytes during all developmental stages. A1AT has hitherto only been found associated...... with azurophile granules in neutrophils indicative of A1AT expression being restricted to the promyelocyte stage. We examined the localization and production of A1AT in healthy donor neutrophils and found A1AT to be a constituent of all granule subtypes and to be released from neutrophils following...

  19. Proteinase 3 contributes to transendothelial migration of NB1-positive neutrophils.

    Science.gov (United States)

    Kuckleburg, Christopher J; Tilkens, Sarah B; Santoso, Sentot; Newman, Peter J

    2012-03-01

    Neutrophil transmigration requires the localization of neutrophils to endothelial cell junctions, in which receptor-ligand interactions and the action of serine proteases promote leukocyte diapedesis. NB1 (CD177) is a neutrophil-expressed surface molecule that has been reported to bind proteinase 3 (PR3), a serine protease released from activated neutrophils. PR3 has demonstrated proteolytic activity on a number of substrates, including extracellular matrix proteins, although its role in neutrophil transmigration is unknown. Recently, NB1 has been shown to be a heterophilic binding partner for the endothelial cell junctional protein, PECAM-1. Disrupting the interaction between NB1 and PECAM-1 significantly inhibits neutrophil transendothelial cell migration on endothelial cell monolayers. Because NB1 interacts with endothelial cell PECAM-1 at cell junctions where transmigration occurs, we considered that NB1-PR3 interactions may play a role in aiding neutrophil diapedesis. Blocking Abs targeting the heterophilic binding domain of PECAM-1 significantly inhibited transmigration of NB1-positive neutrophils through IL-1β-stimulated endothelial cell monolayers. PR3 expression and activity were significantly increased on NB1-positive neutrophils following transmigration, whereas neutrophils lacking NB1 demonstrated no increase in PR3. Finally, using selective serine protease inhibitors, we determined that PR3 activity facilitated transmigration of NB1-positive neutrophils under both static and flow conditions. These data demonstrate that PR3 contributes in the selective recruitment of the NB1-positive neutrophil population. PMID:22266279

  20. Proteases of neutrophilic granulocytes

    Directory of Open Access Journals (Sweden)

    Wiesława Roszkowska-Jakimiec

    2002-06-01

    Full Text Available The literature referring to proteolytic enzymes of neutrophilic granulocytes was surveyed. Biosynthesis, subcellular distribution, division according to the catalytic site structure, inhibitors and methods used to determine the activity of these enzymes were discussed. The survey included metaloproteases (granulocytic collagenase, gelatinase B, serine proteases (granulocytic elastase, cathepsin G, protease 3, membraneous proteases (aminopeptidase N, aminopeptidase P, neprilisine, cysteine and aspartic cathepsins. The role of these proteases in the pathology and diagnostics of certain diseases was considered.

  1. Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro.

    Directory of Open Access Journals (Sweden)

    Irundika H K Dias

    Full Text Available The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 (. - by the nicotinamide adenine dinucleotide (NADPH oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2, a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH/oxidised glutathione (GSSG ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC, and modifier (GCLM subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 (. - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.

  2. Changes in Neutrophil Functions in Astronauts

    Science.gov (United States)

    Kaur, Indreshpal; Simons, Elizabeth R.; Castro, Victoria; Pierson, Duane L.

    2002-01-01

    Neutrophil functions (phagocytosis, oxidative burst, degranulation) and expression of surface markers involved in these functions were studied in 25 astronauts before and after 4 space shuttle missions. Space flight duration ranged from 5 to 11 days. Blood specimens were obtained 10 days before launch (preflight or L-10), immediately after landing (landing or R+0), and again at 3 days after landing (postflight or R+3). Blood samples were also collected from 9 healthy low-stressed subjects at 3 time points simulating a 10-day shuttle mission. The number of neutrophils increased at landing by 85 percent when compared to the preflight numbers. Neutrophil functions were studied in whole blood using flow cytometric methods. Phagocytosis of E.coli-FITC and oxidative burst capacity of the neutrophils following the 9 to 11 day missions were lower at all three sampling points than the mean values for control subjects. Phagocytosis and oxidative burst capacity of the astronauts was decreased even 10-days before space flight. Mission duration appears to be a factor in phagocytic and oxidative functions. In contrast, following the short-duration (5-days) mission, these functions were unchanged from control values. No consistent changes in degranulation were observed following either short or medium length space missions. The expression of CD16, CD32, CD11a, CD11b, CD11c, L-selectin and CD36 was measured and found to be variable. Specifically, CD16 and CD32 did not correlate with the changes in oxidative burst and phagocytosis. We can conclude from this study that the stresses associated with space flight can alter the important functions of neutrophils.

  3. Azithromycin inhibits neutrophil accumulation in airways by affecting interleukin- 17 downstream signals

    Institute of Scientific and Technical Information of China (English)

    Nguyen Van Luu; YANG Jiong; QU Xue-ju; GUO Ming; WANG Xin; XIAN Qiao-yang; TANG Zhi-jiao; HUANG Zhi-xiang; WANG Yong

    2012-01-01

    Background Azithromycin can reduce neutrophil accumulation in neutrophilic pulmonary diseases.However,the precise mechanism behind this action remains unknown.Our experiment assessed whether azithromycin inhibits neutrophil accumulation in the airways by affecting interleukin-17 (IL-17) downstream signals.Methods Mice were pretreated with azithromycin before murine IL-17A (mlL-17) stimulation.After the mlL-17 stimulation,the levels of six neutrophil-mobilizing cytokines were determined by enzyme-linked immunosorbent assay (ELISA) tests in bronchoalveolar lavage (BAL) fluid; IL-6,CXC chemokine ligand-1 (CXCL-1),CXCL-5,macrophage inflammatory protein-2 (MIP-2),granulocyte colony-stimulating factor (G-CSF),and granulocyte macrophage colony-stimulating factor (GM-CSF).The number of neutrophils in BAL fluid were evaluated by cytospin preparations.Results (1) Azithromycin pretreatment significantly inhibited both the release of three neutrophil-mobilizing cytokines (MIP-2,CXCL-5 and GM-CSF) and the accumulation of neutrophils in airways caused by mlL-17 stimulation.(2) The levels of three neutrophil-mobilizing cytokines (IL-6,MIP-2 and GM-CSF) were positively correlated with the numbers of neutrophil in BAL fluid.Conclusions Azithromycin can inhibit neutrophil accumulation in the airways by affecting IL-17 downstream signals.This finding suggests that macrolide antibiotic application might be useful in prevention of neutrophilic pulmonary diseases characterized by high levels of IL-17.

  4. Modulation of neutrophil extracellular trap formation in health and disease

    OpenAIRE

    Hosseinzadeh, Ava

    2015-01-01

    The critical prompt innate immune response is highly built upon the influx of neutrophils from the blood stream to the site of infection. In the battlefield, neutrophils sense pathogen-associated molecular patterns (PAMPs) through their pattern-recognition receptors (PRRs) to launch a number of responses with the goal to defeat the invading pathogen. Neutrophils’ wide spectrum of responses ranges from reactive oxygen species production (ROS), phagocytosis, cytokine and chemokine secretion, an...

  5. Intracellular mechanisms of hydroquinone toxicity on endotoxin-activated neutrophils.

    Science.gov (United States)

    Hebeda, Cristina Bichels; Pinedo, Fernanda Júdice; Bolonheis, Simone Marques; Ferreira, Zulma F; Muscará, Marcelo Nicolas; Teixeira, Simone Aparecida; Farsky, Sandra Helena Poliselli

    2012-11-01

    Circulating neutrophils promptly react to different substances in the blood and orchestrate the beginning of the innate inflammatory response. We have shown that in vivo exposure to hydroquinone (HQ), the most oxidative compound of cigarette smoke and a toxic benzene metabolite, affects circulating neutrophils, making them unresponsive to a subsequent bacterial infection. In order to understand the action of toxic molecular mechanisms on neutrophil functions, in vitro HQ actions on pro-inflammatory mediator secretions evoked by Escherichia coli lipopolysaccharide (LPS) were investigated. Neutrophils from male Wistar rats were cultured with vehicle or HQ (5 or 10 μM; 2 h) and subsequently incubated with LPS (5 μg/ml; 18 h). Hydroquinone treatment impaired LPS-induced nitric oxide (NO), tumour necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 secretions by neutrophils. The toxic effect was not dependent on cell death, reduced expression of the LPS receptor or toll-like receptor-4 (TLR-4) or cell priming, as HQ did not induce reactive oxygen species generation or β(2)integrin membrane expression. The action of toxic mechanisms on cytokine secretion was dependent on reduced gene synthesis, which may be due to decreased nuclear factor κB (NF-κB) nuclear translocation. Conversely, this intracellular pathway was not involved in impaired NO production because HQ treatments only affected inducible nitric oxide synthase protein expression and activity, suggesting posttranscriptional and/or posttranslational mechanisms of action. Altogether, our data show that HQ alters the action of different LPS-activated pathways on neutrophils, which may contribute to the impaired triggering of the host innate immune reaction detected during in vivo HQ exposure. PMID:22717997

  6. Human neutrophil alloantigens systems

    Directory of Open Access Journals (Sweden)

    Elyse Moritz

    2009-09-01

    Full Text Available Neutrophil alloantigens are involved in a variety of clinical conditions including immune neutropenias, transfusion-related acute lung injury (TRALI, refractoriness to granulocyte transfusions and febrile transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens. Currently, seven antigens are assigned to five human neutrophil antigen (HNA systems. The HNA-1a, HNA-1b and HNA-1c antigens have been identified as polymorphic forms of the neutrophil Fcγ receptor IIIb (CD16b, encoded by three alleles. Recently, the primary structure of the HNA-2a antigen was elucidated and the HNA-2a-bearing glycoprotein was identified as a member of the Ly-6/uPAR superfamily, which has been clustered as CD177. The HNA-3a antigen is located on a 70-95 kDa glycoprotein; however, its molecular basis is still unknown. Finally, the HNA-4a and HNA-5a antigens were found to be caused by single nucleotide mutations in the αM (CD11b and αL (CD11a subunits of the leucocyte adhesion molecules (β2 integrins. Molecular and biochemical characterization of neutrophil antigenshave expanded our diagnostic tools by the introduction of genotyping techniques and immunoassays for antibody identification. Further studies in the field of neutrophil immunology will facilitate the prevention and management of transfusion reactions and immune diseases caused by neutrophil antibodies.Os aloantígenos de neutrófilos estão associados a várias condições clínicas como neutropenias imunes, insuficiência pulmonar relacionada à transfusão (TRALI, refratariedade à transfusão de granulócitos, e reações transfusionais febris. Na última década, foi observado considerável progresso na caracterização dos aloantígenos envolvidos nestas condições clínicas. Atualmente sete antígenos estão incluídos em cinco sistemas de antígenos de neutrófilo humano (HNA. Os antígenos HNA-1a, HNA-1b e HNA-1c foram

  7. Pneumolysin activates neutrophil extracellular trap formation.

    Science.gov (United States)

    G Nel, J; Theron, A J; Durandt, C; Tintinger, G R; Pool, R; Mitchell, T J; Feldman, C; Anderson, R

    2016-06-01

    The primary objective of the current study was to investigate the potential of the pneumococcal toxin, pneumolysin (Ply), to activate neutrophil extracellular trap (NET) formation in vitro. Isolated human blood neutrophils were exposed to recombinant Ply (5-20 ng ml(-1) ) for 30-90 min at 37°C and NET formation measured using the following procedures to detect extracellular DNA: (i) flow cytometry using Vybrant® DyeCycle™ Ruby; (ii) spectrofluorimetry using the fluorophore, Sytox(®) Orange (5 μM); and (iii) NanoDrop(®) technology. These procedures were complemented by fluorescence microscopy using 4', 6-diamino-2-phenylindole (DAPI) (nuclear stain) in combination with anti-citrullinated histone monoclonal antibodies to visualize nets. Exposure of neutrophils to Ply resulted in relatively rapid (detected within 30-60 min), statistically significant (P DNA impregnated with both citrullinated histone and myeloperoxidase. Microscopy revealed that NETosis appeared to be restricted to a subpopulation of neutrophils, the numbers of NET-forming cells in the control and Ply-treated systems (10 and 20 ng ml(-1) ) were 4·3 (4·2), 14.3 (9·9) and 16·5 (7·5), respectively (n = 4, P < 0·0001 for comparison of the control with both Ply-treated systems). Ply-induced NETosis occurred in the setting of retention of cell viability, and apparent lack of involvement of reactive oxygen species and Toll-like receptor 4. In conclusion, Ply induces vital NETosis in human neutrophils, a process which may either contribute to host defence or worsen disease severity, depending on the intensity of the inflammatory response during pneumococcal infection. PMID:26749379

  8. Improvement of Secret Image Invisibility in Circulation Image with Dyadic Wavelet Based Data Hiding with Run-Length Coded Secret Images of Which Location of Codes are Determined with Random Number

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2011-09-01

    Full Text Available An attempt is made for improvement of secret image invisibility in circulation images with dyadic wavelet based data hiding with run-length coded secret images of which location of codes are determined by random number. Through experiments, it is confirmed that secret images are almost invisible in circulation images. Also robustness of the proposed data hiding method against data compression of circulation images is discussed. Data hiding performance in terms of invisibility of secret images which are embedded in circulation images is evaluated with the Root Mean Square difference between the original secret image and extracted one from the circulation images. Mean while the conventional Multi-Resolution Analysis (MRA based data hiding is attempted with a variety of parameters, level of MRA and the frequency component location of which secret image is replaced to it and is compared to the proposed method. It is found that the proposed data hiding method is superior to the conventional method. Also the conventional data hiding method is not robust against circulation image processing.

  9. Occupational Neutrophilic Asthma

    Directory of Open Access Journals (Sweden)

    Richard Leigh

    1999-01-01

    Full Text Available Occupational asthma is typically associated with an eosinophilic bronchitis. The case of a 41-year-old woman who developed symptoms of asthma after occupational exposure to metal working fluids is reported. The diagnosis of asthma was confirmed by an forced expiratory volume in 1 s (FEV1 of 1.7 (59% predicted, with 11% reversibility after inhaled bronchodilator and a provocation concentration of methacholine to cause a fall in FEV1 of 20% (PC20 of 0.4 mg/mL. Induced sputum examination showed a marked neutrophilia. Over the next six months, serial sputum analyses confirmed the presence of a marked sterile neutrophilic bronchitis during periods of occupational exposure to metal working fluids, which resolved when the patient was away from work and recurred when she returned to work. The sputum findings were mirrored by corresponding changes in spirometry and PC20 methacholine. The findings indicate the occurrence of occupational asthma associated with an intense, sterile neutrophilic bronchitis after exposure to metal working fluids.

  10. [The expression level of adhesion molecules on neutrophils depending at segmentation of their nuclei].

    Science.gov (United States)

    Kashutin, S L; Danilov, S I; Vereshchagina, E N; Kluchareva, S V

    2013-11-01

    The article deals with results of detection of expression level of adhesion molecules on neutrophils and segmentation of their nuclei. It is established that in conditions of absence of antigen stimulation neutrophils of circulating pool express molecules of L-selectin in 53.34%, LFA-1 molecules in 65.64%, ICAM-1 in 40.51%, LE4-3 in 58.72% and PECAM-1 in 59.74%. The full readiness to realization of phase of sliding, strong adhesion and immediately transmigration itselfis detected in neutrophils with five segments in nucleus. PMID:24640111

  11. Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression

    DEFF Research Database (Denmark)

    Malmström, E; Davidova, A; Mörgelin, M; Linder, A; Larsen, Michael; Qvortrup, Klaus; Nordenfelt, P; Shannon, O; Dzupova, O; Holub, M; Malmström, J; Herwald, H

    2014-01-01

    Early diagnosis of severe infectious diseases is essential for timely implementation of lifesaving therapies. In a search for novel biomarkers in sepsis diagnosis we focused on polymorphonuclear neutrophils (PMNs). Notably, PMNs have their protein cargo readily stored in granules and following...... systemic stimulation an immediate increase of neutrophil-borne proteins can be observed into the circulation of sepsis patients. We applied a combination of mass spectrometry (MS) based approaches, LC-MS/MS and selected reaction monitoring (SRM), to characterise and quantify the neutrophil proteome in...... and, thus, a promising technology to study a complex, dynamic and multifactorial disease such as sepsis....

  12. Role of osteopontin in hepatic neutrophil infiltration during alcoholic steatohepatitis

    International Nuclear Information System (INIS)

    Alcoholic liver disease (ALD) is a major complication of heavy alcohol (EtOH) drinking and is characterized by three progressive stages of pathology: steatosis, steatohepatitis, and fibrosis/cirrhosis. Alcoholic steatosis (AS) is the initial stage of ALD and consists of fat accumulation in the liver accompanied by minimal liver injury. AS is known to render the hepatocytes increasingly sensitive to toxicants such as bacterial endotoxin (LPS). Alcoholic steatohepatitis (ASH), the second and rate-limiting step in the progression of ALD, is characterized by hepatic fat accumulation, neutrophil infiltration, and neutrophil-mediated parenchymal injury. However, the pathogenesis of ASH is poorly defined. It has been theorized that the pathogenesis of ASH involves interaction of increased circulating levels of LPS with hepatocytes being rendered highly sensitive to LPS due to heavy EtOH consumption. We hypothesize that osteopontin (OPN), a matricellular protein (MCP), plays an important role in the hepatic neutrophil recruitment due to its enhanced expression during the early phase of ALD (AS and ASH). To study the role of OPN in the pathogenesis of ASH, we induced AS in male Sprague-Dawley rats by feeding EtOH-containing Lieber-DeCarli liquid diet for 6 weeks. AS rats experienced extensive fat accumulation and minimal liver injury. Moderate induction in OPN was observed in AS group. ASH was induced by feeding male Sprague-Dawley rats EtOH-containing Lieber-DeCarli liquid diet for 6 weeks followed by LPS injection. The ASH rats had substantial neutrophil infiltration, coagulative oncotic necrosis, and developed higher liver injury. Significant increases in the hepatic and circulating levels of OPN was observed in the ASH rats. Higher levels of the active, thrombin-cleaved form of OPN in the liver in ASH group correlated remarkably with hepatic neutrophil infiltration. Finally, correlative studies between OPN and hepatic neutrophil infiltration was corroborated in a simple

  13. Anti-neutrophil cytoplasmic antibodies in rheumatoid arthritis: two case reports and review of literature

    OpenAIRE

    Spoerl David; Pers Yves-Marie; Jorgensen Christian

    2012-01-01

    Abstract Background Anti-neutrophil cytoplasmic antibodies are typically detected in anti-neutrophil cytoplasmic antibody associated vasculitis, but are also present in a number of chronic inflammatory non-vasculitic conditions like rheumatoid arthritis. Rare cases of granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis, a vasculitic disorder frequently associated with the presence of anti-neutrophil cytoplasmic antibodies) in patients with rheumatoid arthritis have be...

  14. Application of Intracellular Alkaline Phosphatase Activity Measurement in Detection of Neutrophil Adherence In Vitro

    OpenAIRE

    Katarzyna Bednarska; Magdalena Klink; Zofia Sulowska

    2006-01-01

    We have proposed the use of the fluorimetric method with 4-methylumbelliferyl phosphate (4-MUP) specific substrate for the alkaline phosphatase determination in the neutrophil adhesion assay. We provide evidence that the endogenous neutrophil alkaline phosphatase (NAP) activity evaluation is reliable to quantify neutrophil adhesion at a wide range of cell numbers (104–106). The results obtained by fluorimetric NAP activity test correlate to the results of adherence evaluated using...

  15. Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

    Directory of Open Access Journals (Sweden)

    Francesca S. M. Tang

    2015-01-01

    Full Text Available Background. Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood and suboptimal (ASubopt asthma symptom control. Methods. Peripheral blood neutrophils from AGood (ACQ 0.75, n=7, and healthy controls (HC (n=9 were stimulated with bacterial (LPS (1 μg/mL, fMLF (100 nM, and viral (imiquimod (3 μg/mL, R848 (1.5 μg/mL, and poly I:C (10 μg/mL surrogates or live rhinovirus (RV 16 (MOI1. Cell-free supernatant was collected after 1 h for neutrophil elastase (NE and matrix metalloproteinase- (MMP- 9 measurements or after 24 h for CXCL8 release. Results. Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. Conclusions. Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.

  16. Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.

    LENUS (Irish Health Repository)

    Fanning, N F

    2012-02-03

    Iodinated contrast media (ICM) can induce apoptosis (programmed cell death) in renal, myocardial and endothelial cells. Following intravascular injection, circulating immune cells are exposed to high concentrations of ICM. As neutrophils constitutively undergo apoptosis we hypothesized that ICM may adversely affect neutrophil survival. Our aim was to investigate the effect of ICM on neutrophil apoptosis. Neutrophils were isolated from healthy subjects and cultured in vitro with ionic (diatrizoate and ioxaglate) and non-ionic (iohexol and iotrolan) ICM. The effect of ICM on neutrophil apoptosis in both unstimulated and lipopolysaccharide-stimulated neutrophils was determined by annexin V flow cytometry. The influence of physicochemical properties of the different ICM on apoptosis of neutrophils was also studied. We further investigated the effects of ICM on key intracellular signal pathways, including p38 mitogen-activated protein kinase (MAPK) by Western blotting, and mitochondrial depolarization and caspase activity by flow cytometry. Isoiodine concentrations (20 mg ml(-1)) of ionic (diatrizoate 69.6+\\/-2.9%; ioxaglate 58.9+\\/-2.0%) and non-ionic (iohexol 57.3+\\/-2.9%; iotrolan 57.1+\\/-2.6%) ICM significantly induced neutrophil apoptosis over control levels (47.7+\\/-1.4%). The apoptotic effect of ICM was influenced by their chemical structure, with ionic ICM having a more significant (p<0.01) apoptotic effect than non-ionic ICM (p<0.05). Furthermore, ICM reversed the anti-apoptotic effect of lipopolysaccharide (1000 ng ml(-1)) treated neutrophils to control levels (23.0+\\/-3.5% to 61.2+\\/-5.3%; n=4; p<0.05). These agents induce apoptosis through a p38 MAPK independent pathway that results in mitochondrial depolarization, and is dependent on caspase activation. As neutrophils play a central role in host response to infection and injury, ICM, through induction of neutrophil apoptosis, could have a significant deleterious effect on host immune defence and

  17. Neutrophilic dermatosis of dorsal hands

    Directory of Open Access Journals (Sweden)

    S Kaur

    2015-01-01

    Full Text Available Sweet′s syndrome is characterized by erythematous tender nodules and plaques over face and extremities. Fever, leukocytosis with neutrophilia, and a neutrophilic infiltrate in the dermis are characteristic features. Neutrophilic dermatosis of dorsal hands is a rare localized variant of Sweet′s syndrome occurring predominantly over dorsa of hands. Various degrees of vascular damage may be observed on histopathology of these lesions. Both Sweet′s syndrome and its dorsal hand variant have been reported in association with malignancies, inflammatory bowel diseases, and drugs. We report a patient with neutrophilic dermatoses of dorsal hands associated with erythema nodosum. He showed an excellent response to corticosteroids and dapsone.

  18. Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1.

    Science.gov (United States)

    Burgener, Sabrina S; Baumann, Mathias; Basilico, Paola; Remold-O'Donnell, Eileen; Touw, Ivo P; Benarafa, Charaf

    2016-09-01

    Serpinb1 is an inhibitor of neutrophil granule serine proteases cathepsin G, proteinase-3 and elastase. One of its core physiological functions is to protect neutrophils from granule protease-mediated cell death. Mice lacking Serpinb1a (Sb1a-/-), its mouse ortholog, have reduced bone marrow neutrophil numbers due to cell death mediated by cathepsin G and the mice show increased susceptibility to lung infections. Here, we show that conditional deletion of Serpinb1a using the Lyz2-cre and Cebpa-cre knock-in mice effectively leads to recombination-mediated deletion in neutrophils but protein-null neutrophils were only obtained using the latter recombinase-expressing strain. Absence of Serpinb1a protein in neutrophils caused neutropenia and increased granule permeabilization-induced cell death. We then generated transgenic mice expressing human Serpinb1 in neutrophils under the human MRP8 (S100A8) promoter. Serpinb1a expression levels in founder lines correlated positively with increased neutrophil survival when crossed with Sb1a-/- mice, which had their defective neutrophil phenotype rescued in the higher expressing transgenic line. Using new conditional and transgenic mouse models, our study demonstrates the presence of a relatively low Serpinb1a protein threshold in neutrophils that is required for sustained survival. These models will also be helpful in delineating recently described functions of Serpinb1 in metabolism and cancer. PMID:27107834

  19. Mycobacterium abscessus induces a limited pattern of neutrophil activation that promotes pathogen survival.

    Directory of Open Access Journals (Sweden)

    Kenneth C Malcolm

    Full Text Available Mycobacterium abscessus is a rapidly growing mycobacterium increasingly detected in the neutrophil-rich environment of inflamed tissues, including the cystic fibrosis airway. Studies of the immune reaction to M. abscessus have focused primarily on macrophages and epithelial cells, but little is known regarding the neutrophil response despite the predominantly neutrophillic inflammation typical of these infections. In the current study, human neutrophils released less superoxide anion in response to M. abscessus than to Staphylococcus aureus, a pathogen that shares common sites of infection. Exposure to M. abscessus induced neutrophil-specific chemokine and proinflammatory cytokine genes. Although secretion of these protein products was confirmed, the quantity of cytokines released, and both the number and level of gene induction, was reduced compared to S. aureus. Neutrophils mediated killing of M. abscessus, but phagocytosis was reduced when compared to S. aureus, and extracellular DNA was detected in response to both bacteria, consistent with extracellular trap formation. In addition, M. abscessus did not alter cell death compared to unstimulated cells, while S. aureus enhanced necrosis and inhibited apoptosis. However, neutrophils augment M. abscessus biofilm formation. The response of neutrophils to M. abscessus suggests that the mycobacterium exploits neutrophil-rich settings to promote its survival and that the overall neutrophil response was reduced compared to S. aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy.

  20. Solar and geomagnetic effects on the frequency of atmospheric circulation types over Europe: an analysis based on a large number of classifications

    Science.gov (United States)

    Huth, Radan; Cahynová, Monika; Kyselý, Jan

    2010-05-01

    Recently, effects of the 11-year solar cycle on various aspects of tropospheric circulation in the Northern Hemisphere in winter have been recognized. One of our previous studies showed a significant solar effect on the frequency of synoptic types from the Hess-Brezowsky catalogue. Here, we use a large collection of varied classifications of circulation patterns, assembled within the COST733 Action "Harmonization and Applications of Weather Types Classifications for European Regions" to detect the solar effect on the frequency of synoptic types. The collection contains both objective and subjective classifications. The advantage of this multi-classification approach is that peculiarities or biases of any single classification (catalogue) that might influence the detected solar signal vanish once a large ensemble of classifications is used. We divide winter months (December to March) into three groups according to the mean monthly solar activity, quantified by the F10.7 flux. The three groups correspond to the minima of the 11-year solar cycle, a moderate solar activity, and solar maxima. Within each group, frequencies of occurrence of individual circulation types are calculated. Differences in the occurrence of individual classes between solar activity groups indicate the presence of a solar activity effect on atmospheric circulation over Europe. Statistical significance of these differences is estimated by a block resampling method. The research is supported by the Grant Agency of the Czech Academy of Sciences, project A300420805, and by the Ministry of Education, Youth, and Sports of the Czech Republic, contract OC115.

  1. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

  2. Fetal Circulation

    Science.gov (United States)

    ... Pressure High Blood Pressure Tools & Resources Stroke More Fetal Circulation Updated:Jul 8,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  3. 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.

  4. Feedback Amplification of Neutrophil Function.

    Science.gov (United States)

    Németh, Tamás; Mócsai, Attila

    2016-06-01

    As the first line of innate immune defense, neutrophils need to mount a rapid and robust antimicrobial response. Recent studies implicate various positive feedback amplification processes in achieving that goal. Feedback amplification ensures effective migration of neutrophils in shallow chemotactic gradients, multiple waves of neutrophil recruitment to the site of inflammation, and the augmentation of various effector functions of the cells. We review here such positive feedback loops including intracellular and autocrine processes, paracrine effects mediated by lipid (LTB4), chemokine, and cytokine mediators, and bidirectional interactions with the complement system and with other immune and non-immune cells. These amplification mechanisms are not only involved in antimicrobial immunity but also contribute to neutrophil-mediated tissue damage under pathological conditions. PMID:27157638

  5. Nitrite is produced by elicited but not by circulating neutrophils

    Directory of Open Access Journals (Sweden)

    A. G. Stewart

    1993-01-01

    Full Text Available The generation of nitrite (NO2− was used as an index of the production of nitric oxide by human and rat polymorphonuclear leukocytes (PMN and rat peritoneal macrophages. Human peripheral blood PMN did not produce significant levels of NO2−. Attempts to induce NO2− generation in human PMN by incubation with GM–CSF (1 nM, TNFα (0.3 nM, endotoxin (1 μg/ml or formyl-Met-Leu-Phe (100 nM for up to 16 h were not successful. Addition of human PMN primed by GM–CSF (1 nM to rabbit aortic ring preparations precontracted with phenylephrine had no effect on tone. In contrast to these observations, PMN, isolated from the peritoneum of oyster glycogen treated rats, generated NO2− via a pathway sensitive to inhibition by the nitric oxide synthase inhibitor, NG-monomethyl L-arginine. However, peripheral blood rat PMN obtained from the same animals did not produce NO2−, even during prolonged incubation for periods of up to 16 h. It is suggested that detectable NO production by PMN requires NO synthase activity to be induced either by the process of PMN migration or by exposure to certain cytokines produced locally at the site of inflammation.

  6. Number of circulating pro‐angiogenic cells, growth factor and anti‐oxidative gene profiles might be altered in type 2 diabetes with and without diabetic foot syndrome

    OpenAIRE

    Witold N. Nowak; Borys, Sebastian; Kusińska, Katarzyna; Bukowska‐Strakova, Karolina; Witek, Przemysław; Koblik, Teresa; Józkowicz, Alicja; Małecki, Maciej Tadeusz; Dulak, Józef

    2013-01-01

    Abstract Aims/Introduction Type 2 diabetes is often complicated by diabetic foot syndrome (DFS). We analyzed the circulating stem cells, growth factor and anti‐oxidant gene expression profiles in type 2 diabetes patients without or with different forms of DFS. Materials and Methods Healthy volunteers (n = 13) and type 2 diabetes patients: (i) without DFS (n = 10); or with (ii) Charcot osteoneuropathy (n = 10); (iii) non‐infected (n = 17); (iv) infected (n = 11); and (v) healed ulceration were...

  7. The effect of glutamine supplementation and physical exercise on neutrophil function.

    Science.gov (United States)

    Lagranha, C J; Levada-Pires, A C; Sellitti, D F; Procopio, J; Curi, R; Pithon-Curi, T C

    2008-04-01

    Glutamine is the most abundant free amino acid in the body. Its primary source is skeletal muscle, from where it is released into the bloodstream and transported to a variety of tissues. Several studies have shown that glutamine is important for rat and human neutrophil function and that these cells utilize glutamine at high rates. Physical exercise has also been shown to induce considerable changes in neutrophil metabolism and function. As neutrophils represent 50-60% of the total circulating leukocyte pool and play a key role in inflammation, both physical exercise and glutamine might be expected to regulate the inflammatory process. In this review, the changes in neutrophil function induced by physical exercise and glutamine supplementation are compared. PMID:17928941

  8. Berberine in combination with yohimbine attenuates sepsis-induced neutrophil tissue infiltration and multiorgan dysfunction partly via IL-10-mediated inhibition of CCR2 expression in neutrophils.

    Science.gov (United States)

    Wang, Yuan; Wang, Faqiang; Yang, Duomeng; Tang, Xiangxu; Li, Hongmei; Lv, Xiuxiu; Lu, Daxiang; Wang, Huadong

    2016-06-01

    Infiltration of activated neutrophils into the vital organs contributes to the multiple organ dysfunctions in sepsis. In the present study, we investigated the effects of berberine in combination with yohimbine (BY) on neutrophil tissue infiltration and multiple organ damage during sepsis, and further elucidated the involved mechanisms. Sepsis was induced in mice by cecal ligation and puncture (CLP). BY or CCR2 antagonist was administered 2h after CLP, and anti-IL-10 antibody (IL-10 Ab) or control IgG was injected intraperitoneally just before BY treatment. We found that IL-10 production was enhanced by BY therapy in septic mice. BY significantly attenuated neutrophil tissue infiltration and multiple organ injury in CLP-challenged mice, all of which were completely reversed by IL-10 Ab pretreatment. The levels of KC, MCP-1, MIP-1α and MIP-2 in the lung, liver and kidney were markedly increased 6h after CLP. BY reduced the tissue concentrations of these chemokines in septic mice, but IL-10 Ab pretreatment did not completely eliminate these inhibitory effects of BY. Particularly, dramatically increased CCR2 expression in circulating neutrophils of septic mice was reduced by BY and this effect was completely abolished by IL-10 Ab pretreatment. Furthermore, CCR2 antagonist also inhibited lung and renal injury and neutrophil infiltration in septic mice. Taken together, our data strongly suggest that BY therapy attenuates neutrophil tissue infiltration and multiple organ injury in septic mice, at least in part, via IL-10-mediated inhibition of CCR2 expression in circulating neutrophils. PMID:27082997

  9. [Defects of neutrophil function in chronic gastroduodenitis in children].

    Science.gov (United States)

    Agafonova, E V; Malanicheva, T G; Denisova, S N

    2013-01-01

    At present, chronic gastroduodenitis (CGD) occupies one ofthe leading places in the structure of diseases of the gastrointestinal tract in children. In the etiology of CGD, along with the leading pathogenic Helicobacterpylori (HP), the role of the fungal flora increased. The aim of the work was to evaluate the functional activity of neutrophils in children with the CGD, associated with HP and Candida albicans. Among 110 children in the age from 7 to 17 years with chronic gastroduodenitis, associated with Helicobacter pylory(HP), as well as the association of HP with Candida albicans and the markers of secondary immune insufficiency, a study of the phagocytic activity and immune phenotype of neutrophils by flow cytofluorimetry was conducted. Differentiated peculiarities of the phagocytic activity of neutrophils in association with bacterial pathogens (HP) and fungal flora were identified. The transformation of the immune phenotype was combined with a significant depression of the phagocytic and microbicidal functions, more pronounced with the association of HP and Candida albicans. Circulating mannano protein antigen of Candida albicans influenced on the surface of phenotype of neutrophils, increasing the expression of protopathic and HLADR-receptors, and decreasing the expression of adhesion receptors and cytolysis. Thus, in case of chronic gastroduodenitis in children, there was a considerable transformation of the phenotype of neutrophil with differentiated characteristics at the association with bacterial (HP) pathogens and fungal flora. The obtained data should be taken into account when carrying out medical activities, and the doctors should include in the composition of complex therapy of CGD, associated with Candida albicans, drugs, aimed at immunocorrection of the identified violations PMID:23951901

  10. Lung Circulation.

    Science.gov (United States)

    Suresh, Karthik; Shimoda, Larissa A

    2016-01-01

    The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed. © 2016 American Physiological Society. Compr Physiol 6:897-943, 2016. PMID:27065170

  11. Stability analysis of micropipette aspiration of neutrophils.

    OpenAIRE

    Derganc, J; Bozic, B; Svetina, S.; Zeks, B.

    2000-01-01

    During micropipette aspiration, neutrophil leukocytes exhibit a liquid-drop behavior, i.e., if a neutrophil is aspirated by a pressure larger than a certain threshold pressure, it flows continuously into the pipette. The point of the largest aspiration pressure at which the neutrophil can still be held in a stable equilibrium is called the critical point of aspiration. Here, we present a theoretical analysis of the equilibrium behavior and stability of a neutrophil during micropipette aspirat...

  12. Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C. David; Bajt, Mary Lynn [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Sharpe, Matthew R. [Department of Internal Medicine, University of Kansas Hospital, Kansas City, KS (United States); McGill, Mitchell R. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Farhood, Anwar [Department of Pathology, St. David' s North Austin Medical Center, Austin, TX 78756 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2014-03-01

    Following acetaminophen (APAP) overdose there is an inflammatory response triggered by the release of cellular contents from necrotic hepatocytes into the systemic circulation which initiates the recruitment of neutrophils into the liver. It has been demonstrated that neutrophils do not contribute to APAP-induced liver injury, but their role and the role of NADPH oxidase in injury resolution are controversial. C57BL/6 mice were subjected to APAP overdose and neutrophil activation status was determined during liver injury and liver regeneration. Additionally, human APAP overdose patients (ALT: > 800 U/L) had serial blood draws during the injury and recovery phases for the determination of neutrophil activation. Neutrophils in the peripheral blood of mice showed an increasing activation status (CD11b expression and ROS priming) during and after the peak of injury but returned to baseline levels prior to complete injury resolution. Hepatic sequestered neutrophils showed an increased and sustained CD11b expression, but no ROS priming was observed. Confirming that NADPH oxidase is not critical to injury resolution, gp91{sup phox}−/− mice following APAP overdose displayed no alteration in injury resolution. Peripheral blood from APAP overdose patients also showed increased neutrophil activation status after the peak of liver injury and remained elevated until discharge from the hospital. In mice and humans, markers of activation, like ROS priming, were increased and sustained well after active liver injury had subsided. The similar findings between surviving patients and mice indicate that neutrophil activation may be a critical event for host defense or injury resolution following APAP overdose, but not a contributing factor to APAP-induced injury. - Highlights: • Neutrophil (PMN) function increases during liver repair after acetaminophen overdose. • Liver repair after acetaminophen (APAP)-overdose is not dependent on NADPH oxidase. • Human PMNs do not appear

  13. Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans

    International Nuclear Information System (INIS)

    Following acetaminophen (APAP) overdose there is an inflammatory response triggered by the release of cellular contents from necrotic hepatocytes into the systemic circulation which initiates the recruitment of neutrophils into the liver. It has been demonstrated that neutrophils do not contribute to APAP-induced liver injury, but their role and the role of NADPH oxidase in injury resolution are controversial. C57BL/6 mice were subjected to APAP overdose and neutrophil activation status was determined during liver injury and liver regeneration. Additionally, human APAP overdose patients (ALT: > 800 U/L) had serial blood draws during the injury and recovery phases for the determination of neutrophil activation. Neutrophils in the peripheral blood of mice showed an increasing activation status (CD11b expression and ROS priming) during and after the peak of injury but returned to baseline levels prior to complete injury resolution. Hepatic sequestered neutrophils showed an increased and sustained CD11b expression, but no ROS priming was observed. Confirming that NADPH oxidase is not critical to injury resolution, gp91phox−/− mice following APAP overdose displayed no alteration in injury resolution. Peripheral blood from APAP overdose patients also showed increased neutrophil activation status after the peak of liver injury and remained elevated until discharge from the hospital. In mice and humans, markers of activation, like ROS priming, were increased and sustained well after active liver injury had subsided. The similar findings between surviving patients and mice indicate that neutrophil activation may be a critical event for host defense or injury resolution following APAP overdose, but not a contributing factor to APAP-induced injury. - Highlights: • Neutrophil (PMN) function increases during liver repair after acetaminophen overdose. • Liver repair after acetaminophen (APAP)-overdose is not dependent on NADPH oxidase. • Human PMNs do not appear to

  14. The crucial role of neutrophil granulocytes in bone fracture healing.

    Science.gov (United States)

    Kovtun, A; Bergdolt, S; Wiegner, R; Radermacher, P; Huber-Lang, M; Ignatius, A

    2016-01-01

    Delayed bone fracture healing and the formation of non-unions represent an important clinical problem, particularly in polytrauma patients who suffer from posttraumatic systemic inflammation. However, the underlying pathomechanisms remain unclear. Neutrophil granulocytes are crucial effector cells in the systemic immune response and represent the most abundant immune cell population in the early fracture haematoma. Here we investigated the role of neutrophils in a mouse model of uncomplicated fracture healing and compromised fracture healing induced by an additional thoracic trauma. Twenty four hours before injury, 50 % of the mice were systemically treated with an anti-Ly-6G-antibody to reduce neutrophil numbers. In the isolated fracture model, Ly-6G-Ab treatment significantly increased the concentration of both pro- and anti-inflammatory cytokines, including interleukin (IL)-6 and IL-10, and chemokines, for example, C-X-C motif ligand 1 (CXCL1) and monocyte chemotactic protein-1 (MCP-1), in the fracture haematoma. Monocyte/macrophage recruitment was also significantly enhanced. After 21 d, bone regeneration was considerably impaired as demonstrated by significantly diminished bone content and impaired mechanical properties of the fracture callus. These results indicate that undisturbed neutrophil recruitment and function in the inflammatory phase after fracture is crucial to initiate downstream responses leading to bone regeneration. In the combined trauma model, the reduction of neutrophil numbers ameliorated pulmonary inflammation but did not provoke any significant effect on bone regeneration, suggesting that neutrophils may not play a crucial pathomechanistic role in compromised fracture healing induced by an additional thoracic trauma. PMID:27452963

  15. Type I interferon transcriptional signature in neutrophils and high frequency of low-density granulocytes are associated with tissue damage in malaria

    Science.gov (United States)

    Rocha, Bruno Coelho; Marques, Pedro Elias; Leoratti, Fabiana Maria de Souza; Junqueira, Caroline; Pereira, Dhelio Batista; Antonelli, Lis Ribeiro do Valle; Menezes, Gustavo Batista

    2015-01-01

    SUMMARY Neutrophils are the most abundant leukocyte population in the bloodstream, the primary compartment of Plasmodium sp. infection. Yet, the role of these polymorphonuclear cells in mediating either resistance or pathogenesis of malaria is poorly understood. We report that circulating neutrophils from malaria patients are highly activated, as indicated by a strong type I interferon transcriptional signature, increased expression of surface activation markers, the enhanced release of reactive oxygen species and myeloperoxidase, as well as the high frequency of low-density granulocytes. The activation of neutrophils was associated with increased levels of serum alanine and aspartate aminotransferases, indicating liver damage. In a rodent malaria model, we observed an intense recruitment of neutrophils to liver sinusoids. Neutrophil migration, IL-1β and chemokine expression as well as liver damage were all dependent on type I interferon signaling. The data suggests that type I interferon signaling have a central role in neutrophil activation and malaria pathogenesis. PMID:26711347

  16. Application of intracellular alkaline phosphatase activity measurement in detection of neutrophil adherence in vitro.

    Science.gov (United States)

    Bednarska, Katarzyna; Klink, Magdalena; Sulowska, Zofia

    2006-01-01

    We have proposed the use of the fluorimetric method with 4-methylumbelliferyl phosphate (4-MUP) specific substrate for the alkaline phosphatase determination in the neutrophil adhesion assay. We provide evidence that the endogenous neutrophil alkaline phosphatase (NAP) activity evaluation is reliable to quantify neutrophil adhesion at a wide range of cell numbers (10(4)-10(6)). The results obtained by fluorimetric NAP activity test correlate to the results of adherence evaluated using the MTT reduction assay. The fluorimetric NAP activity test may be applied for resting as well as activated neutrophils without the risk of the activators interferences into the test. The alkaline phosphatase survey with the use of 4-MUP substrate is recommended herein as a sensitive, repeatable, simple, and reliable method of the neutrophil adherence determination in vitro. PMID:17047286

  17. Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis

    Science.gov (United States)

    Alves-Filho, Jose C.; Freitas, Andressa; Souto, Fabricio O.; Spiller, Fernando; Paula-Neto, Heitor; Silva, Joao S.; Gazzinelli, Ricardo T.; Teixeira, Mauro M.; Ferreira, Sergio H.; Cunha, Fernando Q.

    2009-01-01

    Patients with sepsis have a marked defect in neutrophil migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of neutrophil migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of neutrophil migration. Moreover, TLR2−/− mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, neutrophils activated ex vivo by LTA and adoptively transferred into naïve WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein–coupled receptor kinases 2 (GRK2) in neutrophils; increased expression of GRK2 was seen in blood neutrophils from WT mice, but not TLR2−/− mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis. PMID:19234125

  18. EMR2 Receptor Ligation Modulates Cytokine Secretion Profiles and Cell Survival of Lipopolysaccharide-treated Neutrophils

    Directory of Open Access Journals (Sweden)

    Tzu-Ying Chenee

    2011-10-01

    Full Text Available Background: Epidermal growth factor (EGF-like module-containing mucin-like hormonereceptor-like 2 (EMR2 is an adhesion G protein-coupled receptor previouslyshown to potentiate neutrophil responses to a number of inflammatory stimuli. EMR2 activation promotes neutrophil adhesion and migration, and augments production of reactive oxygen species and degranulation. In this study,we examined the effect of EMR2 ligation by its specific antibody on thecytokine expression profile and cell survival of lipopolysaccharide (LPS-treated neutrophils.Methods: Neutrophils were treated with LPS in the absence or presence of the antiEMR2 mAb, 2A1. Cell apoptosis was determined by flow cytometry analysisusing annexin-V and propidium iodide staining. Cell supernatants were collected for the detection of cytokine secretion by enzyme-linked immunosorbent assay.Results: We confirmed the specific priming effect of EMR2 on the response of neutrophils to formyl-Met-Leu-Phe by measuring the production of reactiveoxygen species. Furthermore, we showed that EMR2 ligation suppressesLPS-induced neutrophil survival. In addition, we demonstrated that ligationof EMR2 changes the secretion profiles of multiple cytokines, includinginterleukin (IL-6, IL-8, and monocyte chemotactic protein-1. Finally, higherlevels of EMR2 were detected on neutrophils of liver cirrhosis patients andwere correlated to a pro-apoptotic phenotype.Conclusion: Collectively, the present data indicate a functional role for EMR2 in themodulation of neutrophil activation during inflammation.

  19. The Effects of Pterostilbene on Neutrophil Activity in Experimental Model of Arthritis

    Directory of Open Access Journals (Sweden)

    Tomas Perecko

    2013-01-01

    Full Text Available It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophils in vitro. However, little is known about its effects on neutrophils during inflammation in vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model. Lewis rats were injected by a single intradermal injection of heat-killed Mycobacterium butyricum in Freund’s adjuvant to develop arthritis. Another group of arthritic animals received pterostilbene 30 mg/kg, daily, p.o. The number and activity of neutrophils in blood were measured on a weekly basis during the whole experiment. Moreover, the total radical trapping potential in plasma was measured at the end of the experiment. In the pterostilbene treated arthritic group, the treatment significantly lowered the number of neutrophils in blood on days 14 and 21 without significant downregulation of neutrophil oxidative burst. Pterostilbene nonsignificantly increased total radical trapping potential in arthritic animals. These results indicate that the promising effects of pterostilbene on reactive oxygen species operate by different mechanisms in vitro and in the animal model of inflammation. In conclusion, the positive effects of pterostilbene in the model of arthritis may be attributed to regulation of neutrophil number.

  20. Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke

    Directory of Open Access Journals (Sweden)

    Machado Livia S

    2005-08-01

    Full Text Available Abstract Background While gelatinase (MMP-2 and -9 activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown. Results Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9 expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change. Conclusion The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke.

  1. Neutrophil extracellular traps - the dark side of neutrophils.

    Science.gov (United States)

    Sørensen, Ole E; Borregaard, Niels

    2016-05-01

    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 originally described in vitro. Citrullination of histones by peptidyl arginine deiminase 4 (PAD4) is central for NET formation in vivo. NETs may spur formation of autoantibodies and may also serve as scaffolds for thrombosis, thereby providing a link among infection, autoimmunity, and thrombosis. In this review, we present the mechanisms by which NETs are formed and discuss the physiological and pathophysiological consequences of NET formation. We conclude that NETs may be of more importance in autoimmunity and thrombosis than in innate immune defense. PMID:27135878

  2. 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.

  3. 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.

  4. Trace element landscape of resting and activated human neutrophils on the sub-micrometer level.

    Science.gov (United States)

    Niemiec, M J; De Samber, B; Garrevoet, J; Vergucht, E; Vekemans, B; De Rycke, R; Björn, E; Sandblad, L; Wellenreuther, G; Falkenberg, G; Cloetens, P; Vincze, L; Urban, C F

    2015-06-01

    Every infection is a battle for trace elements. Neutrophils migrate first to the infection site and accumulate quickly to high numbers. They fight pathogens by phagocytosis and intracellular toxication. Additionally, neutrophils form neutrophil extracellular traps (NETs) to inhibit extracellular microbes. Yet, neutrophil trace element characteristics are largely unexplored. We investigated unstimulated and phorbol myristate acetate-stimulated neutrophils using synchrotron radiation X-ray fluorescence (SR-XRF) on the sub-micron spatial resolution level. PMA activates pinocytosis, cytoskeletal rearrangements and the release of NETs, all mechanisms deployed by neutrophils to combat infection. By analyzing Zn, Fe, Cu, Mn, P, S, and Ca, not only the nucleus but also vesicular granules were identifiable in the elemental maps. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) revealed a neutrophil-specific composition of Zn, Fe, Cu, and Mn in comparison with J774 and HeLa cells, indicating a neutrophil-specific metallome complying with their designated functions. When investigating PMA-activated neutrophils, the SR-XRF analysis depicted typical subcellular morphological changes: the transformation of nucleus and granules and the emergence of void vacuoles. Mature NETs were evenly composed of Fe, P, S, and Ca with occasional hot spots containing Zn, Fe, and Ca. An ICP-MS-based quantification of NET supernatants revealed a NETosis-induced decrease of soluble Zn, whereas Fe, Cu, and Mn concentrations were only slightly affected. In summary, we present a combination of SR-XRF and ICP-MS as a powerful tool to analyze trace elements in human neutrophils. The approach will be applicable and valuable to numerous aspects of nutritional immunity. PMID:25832493

  5. Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation

    Directory of Open Access Journals (Sweden)

    Ramesh Natarajan

    2013-08-01

    Full Text Available Introduction: Neutrophil extracellular trap (NET formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC is protective in sepsis. Whether VitC alters NETosis is unknown. Methods: We used Gulo−/− mice as they lack the ability to synthesize VitC. Sepsis was induced by intraperitoneal infusion of a fecal stem solution (abdominal peritonitis, FIP. Some VitC deficient Gulo−/− mice received an infusion of ascorbic acid (AscA, 200 mg/kg 30 min after induction of FIP. NETosis was assessed histologically and by quantification for circulating free DNA (cf-DNA in serum. Autophagy, histone citrullination, endoplasmic reticulum (ER stress, NFκB activation and apoptosis were investigated in peritoneal PMNs. Results: Sepsis produced significant NETs in the lungs of VitC deficient Gulo−/− mice and increased circulating cf-DNA. This was attenuated in the VitC sufficient Gulo−/− mice and in VitC deficient Gulo−/− mice infused with AscA. Polymorphonuclear neutrophils (PMNs from VitC deficient Gulo−/− mice demonstrated increased activation of ER stress, autophagy, histone citrullination, and NFκB activation, while apoptosis was inhibited. VitC also significantly attenuated PMA induced NETosis in PMNs from healthy human volunteers.

  6. 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.

  7. [Ambiguity role of neutrophils in oncogenesis].

    Science.gov (United States)

    Mal'tseva, V N; Safronova, V G

    2009-01-01

    The review is focused on the participation of polymorphonuclear granulocytes (neutrophils) in development and spreading of a tumor. We consider both the well known functions of neutrophils (degranulation, production of reactive oxygen species (ROS)) and the recently shown one (presentation of an antigene). The special attention is focused on the ambiguity of the neutrophil role in oncogenesis. The dominant view is that neutrophils display exclusively antitumor properties. The update information testifies about protumoral activity of neutrophils: they migrate to a tumor and promote angiogenesis and metastasis at late stages of the tumor. It is interesting that certain components of neutrophil cytotoxic arsenal (ROS, cytokines, specific enzymes) participate both in antitumoral defenses of an organism and protumoral activity. PMID:19637749

  8. Different Leishmania Species Drive Distinct Neutrophil Functions.

    Science.gov (United States)

    Hurrell, Benjamin P; Regli, Ivo B; Tacchini-Cottier, Fabienne

    2016-05-01

    Leishmaniases are vector-borne diseases of serious public health importance. During a sand fly blood meal, Leishmania parasites are deposited in the host dermis where neutrophils are rapidly recruited. Neutrophils are the first line of defense and can kill pathogens by an array of mechanisms. They can also form web-like structures called neutrophil extracellular traps (NETs) that can trap and/or kill microbes. The function of neutrophils in leishmaniasis was reported to be either beneficial by contributing to parasite killing or detrimental by impairing immune response development and control of parasite load. Here we review recent data showing that different Leishmania species elicit distinct neutrophil functions thereby influencing disease outcomes. Emerging evidence suggests that neutrophils should be considered important modulators of leishmaniasis. PMID:26944469

  9. Endogenous morphine levels are increased in sepsis: a partial implication of neutrophils.

    Directory of Open Access Journals (Sweden)

    Elise Glattard

    Full Text Available BACKGROUND: Mammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear. We postulate that morphine is released during infection and can be determined in the serum of patients with severe infection such as sepsis. METHODOLOGY: The presence and subcellular immunolocalization of endogenous morphine was investigated by ELISA, mass spectrometry analysis and laser confocal microscopy. Neutrophils were activated with Interleukin-8 (IL-8 or lipopolysaccharide (LPS. Morphine secretion was determined by a morphine-specific ELISA. mu opioid receptor expression was assessed with flow cytometry. Serum morphine concentrations of septic patients were determined with a morphine-specific ELISA and morphine identity was confirmed in human neutrophils and serum of septic patients by mass spectrometry analysis. The effects of the concentration of morphine found in serum of septic patients on LPS-induced release of IL-8 by human neutrophils were tested. PRINCIPAL FINDINGS: We confirmed the presence of morphine in human neutrophil extracts and showed its colocalisation with lactoferrin within the secondary granules of neutrophils. Morphine secretion was quantified in the supernatant of activated human polymorphonuclear neutrophils in the presence and absence of Ca(2+. LPS and IL-8 were able to induce a significant release of morphine only in presence of Ca(2+. LPS treatment increased mu opioid receptor expression on neutrophils. Low concentration of morphine (8 nM significantly inhibited the release of IL-8 from neutrophils when coincubated with LPS. This effect was reversed by naloxone. Patients with sepsis, severe sepsis and septic shock had significant higher circulating morphine levels compared to patients with systemic inflammatory response

  10. Neutrophil degranulation by Helicobacter pylori proteins.

    OpenAIRE

    Nøorgaard, A; Andersen, L P; Nielsen, H

    1995-01-01

    Mucosal biopsy specimens from patients with Helicobacter pylori infection in gastric antrum contain an increased amount of myeloperoxidase. This study was performed to elucidate the interaction of H pylori sonicate protein(s) and neutrophils concerning myeloperoxidase release. Neutrophil degranulation with myeloperoxidase release was examined in a direct stimulating assay. Priming activity of H pylori was examined after preincubating neutrophils in sonicate, either crude or modified by heat t...

  11. Laminin promotes rabbit neutrophil motility and attachment.

    OpenAIRE

    Terranova, V P; DiFlorio, R; Hujanen, E S; Lyall, R M; Liotta, L A; Thorgeirsson, U.; Siegal, G. P.; Schiffmann, E

    1986-01-01

    Polymorphonuclear neutrophils (PMN) traverse basement membrane to reach sites of infection. We have studied the role of laminin, a specific basement membrane component, in this process using three assay systems. In the Boyden chamber, laminin was found to stimulate chemotaxis of neutrophils while fibronectin did not. Co-incubation of cells with antibody to laminin blocked this chemotaxis, while antibody to fibronectin was without effect. In the human amnion system, neutrophils were shown to p...

  12. Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides

    Science.gov (United States)

    Totti, Noel; McCusker, Kevin T.; Campbell, Edward J.; Griffin, Gail L.; Senior, Robert M.

    1984-01-01

    Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at ~ 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

  13. Increased Numbers of Circulating CD8 Effector Memory T Cells before Transplantation Enhance the Risk of Acute Rejection in Lung Transplant Recipients

    Science.gov (United States)

    San Segundo, David; Ballesteros, María Ángeles; Naranjo, Sara; Zurbano, Felipe; Miñambres, Eduardo; López-Hoyos, Marcos

    2013-01-01

    The effector and regulatory T cell subpopulations involved in the development of acute rejection episodes in lung transplantation remain to be elucidated. Twenty-seven lung transplant candidates were prospectively monitored before transplantation and within the first year post-transplantation. Regulatory, Th17, memory and naïve T cells were measured in peripheral blood of lung transplant recipients by flow cytometry. No association of acute rejection with number of peripheral regulatory T cells and Th17 cells was found. However, effector memory subsets in acute rejection patients were increased during the first two months post-transplant. Interestingly, patients waiting for lung transplant with levels of CD8+ effector memory T cells over 185 cells/mm3 had a significant increased risk of rejection [OR: 5.62 (95% CI: 1.08-29.37), p=0.04]. In multivariate analysis adjusted for age and gender the odds ratio for rejection was: OR: 5.89 (95% CI: 1.08-32.24), p=0.04. These data suggest a correlation between acute rejection and effector memory T cells in lung transplant recipients. The measurement of peripheral blood CD8+ effector memory T cells prior to lung transplant may define patients at high risk of acute lung rejection. PMID:24236187

  14. Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages

    Science.gov (United States)

    Zec, Kristina; Volke, Julia; Vijitha, Nirojah; Thiebes, Stephanie; Gunzer, Matthias; Kurts, Christian; Engel, Daniel Robert

    2016-01-01

    The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C+ and Ly6C− macrophage-subtypes and neutrophils in the context of urinary tract infection (UTI) with uropathogenic E. coli (UPEC). Ly6C− macrophages acted as tissue resident sentinels and attracted circulating phagocytes by chemokines. Ly6C+ macrophages produced tumor necrosis factor (TNF) that licensed Ly6C− macrophages to release preformed CXCL2, which in turn caused matrix metalloproteinases (MMP-9) secretion by neutrophils to enable transepithelial migration. PMID:26861402

  15. Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages

    Directory of Open Access Journals (Sweden)

    Kristina Zec

    2016-02-01

    Full Text Available The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C+ and Ly6C− macrophage-subtypes and neutrophils in the context of urinary tract infection (UTI with uropathogenic E. coli (UPEC. Ly6C− macrophages acted as tissue resident sentinels and attracted circulating phagocytes by chemokines. Ly6C+ macrophages produced tumor necrosis factor (TNF that licensed Ly6C− macrophages to release preformed CXCL2, which in turn caused matrix metalloproteinases (MMP-9 secretion by neutrophils to enable transepithelial migration.

  16. Effects of thalidomide on neutrophil respiratory burst, chemotaxis, and transmigration of cytokine- and endotoxin-activated endothelium.

    Science.gov (United States)

    Dunzendorfer, S; Schratzberger, P; Reinisch, N; Kähler, C M; Wiedermann, C J

    1997-11-01

    Vascular endothelium activated by endotoxin and cytokines plays an important role in organ inflammation and blood leukocyte recruitment. Neutrophils, which are a homogeneous population of effector cells, are rapidly attracted in large numbers to sites of inflammation where they form an early response to infection or injury. Excessive production of various interleukins, TNF, arachidonic acid metabolites, and other substances by neutrophils and macrophages results in systemic endothelial cell injury, a fundamental problem. In the present study, we investigated in vitro the effects of thalidomide (THD) on activation of endothelial cells for enhanced transmigration of neutrophils by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF), and interleukin-1 (IL-1). Modulation of endotoxin- and cytokine-induced neutrophil chemotaxis and respiratory burst by THD were also studied. Treatment of HUVEC with THD in combination with LPS, TNF, and IL-1, respectively, antagonized LPS-activated transmigration of neutrophils but stimulated the effects of TNF and IL-1. All of the agents used-THD, LPS, TNF, and IL-1-inhibited neutrophil chemotaxis. Addition of THD to the neutrophils had no effect on LPS-inhibited chemotaxis whereas the TNF- and IL-1-induced chemotaxis was modulated in a bimodal manner. However, THD failed to influence neutrophil respiratory burst activity. Results demonstrate that THD differentially affects mediator-induced activation of HUVEC and neutrophils. PMID:9402031

  17. Serum and Glucocorticoid-Regulated Kinase 1 Regulates Neutrophil Clearance during Inflammation Resolution

    OpenAIRE

    Burgon, Joseph; Robertson, Anne L.; Sadiku, Pranvera; Wang, Xingang; Hooper-Greenhill, Edward; Prince, Lynne R.; Walker, Paul; Hoggett, Emily E.; Ward, Jonathan R.; Farrow, Stuart N.; William J Zuercher; Jeffrey, Philip; Savage, Caroline O.; Ingham, Philip W.; Hurlstone, Adam F.

    2014-01-01

    The inflammatory response is integral to maintaining health by functioning to resist microbial infection and repair tissue damage. Large numbers of neutrophils are recruited to inflammatory sites to neutralize invading bacteria through phagocytosis and the release of proteases and reactive oxygen species into the extracellular environment. Removal of the original inflammatory stimulus must be accompanied by resolution of the inflammatory response, including neutrophil clearance, to prevent in...

  18. Serum and Glucocorticoid Regulated Kinase 1 (SGK1) Regulates Neutrophil Clearance During Inflammation Resolution

    OpenAIRE

    Burgon, Joseph; Robertson, Anne L.; Sadiku, Pranvera; Wang, Xingang; Hooper-Greenhill, Edward; Prince, Lynne R.; Walker, Paul; Hoggett, Emily E.; Ward, Jonathan R.; Farrow, Stuart N.; William J Zuercher; Jeffrey, Philip; Savage, Caroline O.; Ingham, Philip W.; Hurlstone, Adam F.

    2014-01-01

    The inflammatory response is integral to maintaining health, by functioning to resist microbial infection and repair tissue damage. Large numbers of neutrophils are recruited to inflammatory sites to neutralise invading bacteria through phagocytosis and the release of proteases and reactive oxygen species into the extracellular environment. Removal of the original inflammatory stimulus must be accompanied by resolution of the inflammatory response, including neutrophil clearance, to prevent i...

  19. Serum and Glucocorticoid Regulated Kinase 1 (SGK1) Regulates Neutrophil Clearance During Inflammation Resolution

    Science.gov (United States)

    Burgon, Joseph; Robertson, Anne L.; Sadiku, Pranvera; Wang, Xingang; Hooper-Greenhill, Edward; Prince, Lynne R.; Walker, Paul; Hoggett, Emily E.; Ward, Jonathan R.; Farrow, Stuart N.; Zuercher, William J.; Jeffrey, Philip; Savage, Caroline O.; Ingham, Philip W.; Hurlstone, Adam F.; Whyte, Moira K. B.; Renshaw, Stephen A.

    2013-01-01

    The inflammatory response is integral to maintaining health, by functioning to resist microbial infection and repair tissue damage. Large numbers of neutrophils are recruited to inflammatory sites to neutralise invading bacteria through phagocytosis and the release of proteases and reactive oxygen species into the extracellular environment. Removal of the original inflammatory stimulus must be accompanied by resolution of the inflammatory response, including neutrophil clearance, to prevent inadvertent tissue damage. Neutrophil apoptosis and its temporary inhibition by survival signals provides a target for anti-inflammatory therapeutics, making it essential to better understand this process. GM-CSF, a neutrophil survival factor, causes a significant increase in mRNA levels for the known anti-apoptotic protein Serum and Glucocorticoid Regulated Kinase 1 (SGK1). We have characterised the expression patterns and regulation of SGK family members in human neutrophils, and shown that inhibition of SGK activity completely abrogates the anti-apoptotic effect of GM-CSF. Using a transgenic zebrafish model, we have disrupted sgk1 gene function and shown this specifically delays inflammation resolution, without altering neutrophil recruitment to inflammatory sites in vivo. These data suggest SGK1 plays a key role in regulating neutrophil survival signalling, and thus may prove a valuable therapeutic target for the treatment of inflammatory disease. PMID:24431232

  20. Serum and glucocorticoid-regulated kinase 1 regulates neutrophil clearance during inflammation resolution.

    Science.gov (United States)

    Burgon, Joseph; Robertson, Anne L; Sadiku, Pranvera; Wang, Xingang; Hooper-Greenhill, Edward; Prince, Lynne R; Walker, Paul; Hoggett, Emily E; Ward, Jonathan R; Farrow, Stuart N; Zuercher, William J; Jeffrey, Philip; Savage, Caroline O; Ingham, Philip W; Hurlstone, Adam F; Whyte, Moira K B; Renshaw, Stephen A

    2014-02-15

    The inflammatory response is integral to maintaining health by functioning to resist microbial infection and repair tissue damage. Large numbers of neutrophils are recruited to inflammatory sites to neutralize invading bacteria through phagocytosis and the release of proteases and reactive oxygen species into the extracellular environment. Removal of the original inflammatory stimulus must be accompanied by resolution of the inflammatory response, including neutrophil clearance, to prevent inadvertent tissue damage. Neutrophil apoptosis and its temporary inhibition by survival signals provides a target for anti-inflammatory therapeutics, making it essential to better understand this process. GM-CSF, a neutrophil survival factor, causes a significant increase in mRNA levels for the known anti-apoptotic protein serum and glucocorticoid-regulated kinase 1 (SGK1). We have characterized the expression patterns and regulation of SGK family members in human neutrophils and shown that inhibition of SGK activity completely abrogates the antiapoptotic effect of GM-CSF. Using a transgenic zebrafish model, we have disrupted sgk1 gene function and shown this specifically delays inflammation resolution, without altering neutrophil recruitment to inflammatory sites in vivo. These data suggest SGK1 plays a key role in regulating neutrophil survival signaling and thus may prove a valuable therapeutic target for the treatment of inflammatory disease. PMID:24431232

  1. Morphology and staining behavior of neutrophilic and eosinophilic granulocytes of the common marmoset (Callithrix jacchus).

    Science.gov (United States)

    Bleyer, Martina; Curths, Christoph; Dahlmann, Franziska; Wichmann, Judy; Bauer, Natali; Moritz, Andreas; Braun, Armin; Knauf, Sascha; Kaup, Franz-Josef; Gruber-Dujardin, Eva

    2016-06-01

    Common marmosets (Callithrix jacchus) are frequently used as translational animal models for human diseases. However, a comparative study of cytological and histochemical detection methods as well as morphometric and ultrastructural characterization of neutrophils and eosinophils in this species is lacking. Blood samples of house dust mite sensitized and allergen challenged as well as lipopolysaccharide (LPS) challenged marmosets were analyzed with different cytological and histological staining methods. Furthermore, cell size and number of nuclear segments were compared between neutrophils and eosinophils. Electron microscopy was performed to characterize the ultrastructure of granulocytes. Of all applied cytological stains, three allowed differentiation of eosinophils and neutrophils and, thus, reliable quantification in blood smears: May-Grünwald-Giemsa stain, Congo Red and Naphthol AS-D Chloroacetate-Esterase. For histology, Hematoxylin-Eosin (H&E) could not demonstrate clear differences, whereas Sirius Red, Congo Red, and Naphthol AS-D Chloroacetate Esterase showed capable results for identification of eosinophils or neutrophils in lung tissue. Morphometry revealed that marmoset neutrophils have more nuclear segments and are slightly larger than eosinophils. Ultrastructurally, eosinophils presented with large homogeneous electron-dense granules without crystalloid cores, while neutrophils were characterized by heterogeneous granules of different size and density. Additionally, sombrero-like vesicles were detected in tissue eosinophils of atopic marmosets, indicative for hypersensitivity-related piecemeal degranulation. In conclusion, we provide a detailed overview of marmoset eosinophils and neutrophils, important for phenotypic characterization of marmoset models for human airway diseases. PMID:27165445

  2. Effects of copper-aspirin complex on platelet-neutrophil interactions

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang SHEN; Peng CHEN; Ling LI; Peng CHEN; Wei-ping LIU

    2004-01-01

    AIM: To investigate the effects of copper-aspirin complex on rat thrombosis and the interaction between platelets and neutrophils. METHODS: The model of electrically stimulated carotid artery thrombosis in Sprague Dawley rats was used; the effects of copper-aspirin complex on rat platelet-neutrophil adhesion and platelet aggregation stimulated by activated neutrophils were observed by rosette assay and Born's method, respectively. RESULTS:Intragastric copper-aspirin complex (5, 7, and 10 mg/kg) dose-dependently prolonged the occlusion time; it significantly decreased the rosette number formed between thrombin-activated platelets and neutrophils; the 50 % of inhibitory concentration (IC50) was (54.6±4.3) μmol/L. Copper-aspirin complex markedly inhibited rat platelet aggregation induced by either cell free supernatant of activated neutrophils or by activated neutrophil suspension.The values of IC50 were (224.5±16.2) μmol/L and (820.5±21.4) μmol/L, whereas aspirin had no influence.CONCLUSION: Copper-aspirin complex inhibited platelet-neutrophil interactions through a different property from aspirin and resulted in a more potent antithrombotic activity.

  3. Transendothelial migration enhances integrin-dependent human neutrophil chemokinesis

    Science.gov (United States)

    Transendothelial migration of neutrophils induces phenotypic changes that influence the interactions of neutrophils with extravascular tissue components. To assess the influence of transmigration on neutrophil chemokinetic motility, we used polyethylene glycol hydrogels covalently modified with spec...

  4. Tumour necrosis factor-alpha and interleukin-8 inhibit neutrophil migration in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    F. Q. Cunha

    1992-01-01

    Full Text Available Pretreatment of human neutrophils with recombinant tumour necrosis factor-alpha (rTNF-α and/or interleukin-8 (rIL-8, but not with either transforming growth factor-beta, interleukin-6 or interferon-gamma, rendered these cells less responsive to FMLP, in microchemotaxis assays. This inhibitory effect was dose dependent and more powerful when neutrophils were pretreated with a mixture of both cytokines. Intravenous injection of human rIL-8 (hrIL-8 and/or murine rTNF-α (mrTNF-α also significantly reduced in vivo neutrophil migration into peritoneal cavities of rats stimulated with carrageenan. These data suggest that the defect in neutrophil migration during septicaemia or endotoxaemia may be the result of the continuous release of IL-8 and TNF-α into the circulation. Thus, either the selective control or blockade of releasing of these cytokines as well as of its effects on neutrophils may be clinically useful in reestablishing the cell defence mechanisms.

  5. [PHENOTYPE OF PERIPHERAL BLOOD NEUTROPHILS IN THE INITIAL STAGE OF ENDOMETRIAL CANCER].

    Science.gov (United States)

    Abakumova, T V; Antoneeva, I I; Gening, T P; Dolgova, D R; Gening, S O

    2016-01-01

    We have examined peripheral blood neutrophils from 123 patients with primary endometrial cancer at stage Ia. Receptor system and the ability of neutrophils to form extracellular traps were assessed by fluorescence microscopy, the spontaneous production of cytokines IL-2, IFN-γ, g-CSF, matrix metalloproteinases-1,9,13 by the method of enzyme-linked immunosorbent assay, phagocytic activity, myeloperoxidase activity, the level of cationic proteis activity in NBT-test were evaluated by cytochemical methods, activity of neutrophils in the spontaneous NBT-test was used to evaluate the oxygen-dependent bactericidal action of neutrophils. The topology and the rigidity of the membrane of neutrophils were assessed by scanning probe microscopy. We have shown that the increase in the relative number of neutrophils lead to a change in their receptor system, aerobic and anaerobic cytotoxicity and ability to phagocytosis are enchanced while reducing NET-activity. We have observed a change in the secretory activity of neutrophils, which is characterized by increased level of MMP-1, possibly initiated by enhanced production of reactive oxygen species, by a reduction in the IL-2 level (inductor of cytotoxic activity) and a sharp increase in the level of the G-CSF. Architectonics of neutrophils in the case of endonetrial cancer at stage Ia is characterized by changing the shape and loss of grit. The rigidity of the cell membrane decreased. Changes in the morphology of neutrophils on the background of the continuing hyperactivity suggests that a state of balance between the immune system and the tumor is already in stage Ia endometrial cancer. PMID:27220248

  6. Intravascular Neutrophil Activation Due to Carbon Monoxide Poisoning

    OpenAIRE

    Thom, Stephen R.; Bhopale, Veena M.; Han, Shih-Tsung; Clark, James M.; HARDY, KEVIN R.

    2006-01-01

    Rationale: We hypothesized that platelet–neutrophil interactions occur as a result of acute carbon monoxide (CO) poisoning, and subsequent neutrophil activation triggers events that cause neurologic sequelae.

  7. Neutrophilic dermatoses: pyoderma gangrenosum and Sweet's syndrome.

    OpenAIRE

    Lear, J. T.; Atherton, M. T.; Byrne, J. P.

    1997-01-01

    Pyoderma gangrenosum and Sweet's syndrome are classified as neutrophilic dermatoses as they exhibit intense dermal inflammatory infiltrates composed of neutrophils with little evidence of a primary vasculitis. They share several characteristics and respond to immunosuppressives. Aetiology is felt to represent a manifestation of altered immunologic reactivity. Patients with both conditions concurrently have been described. Diagnosis is based on clinical and histopathological findings. However,...

  8. Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactions.

    Science.gov (United States)

    Bain, Barbara J; Ahmad, Shahzaib

    2015-11-01

    Many cases reported as 'chronic neutrophilic leukaemia' have had an associated plasma cell neoplasm. Recent evidence suggests that the great majority of such cases represent a neutrophilic leukaemoid reaction to the underlying multiple myeloma or monoclonal gammopathy of undetermined significance. We have analysed all accessible reported cases to clarify the likely diagnosis and to ascertain whether toxic granulation, Döhle bodies and an increased neutrophil alkaline phosphatase score were useful in making a distinction between chronic neutrophilic leukaemia and a neutrophilic leukaemoid reaction. We established that all these changes occur in both conditions. Toxic granulation and Döhle bodies are more consistently present in leukaemoid reactions but also occur quite frequently in chronic neutrophilic leukaemia. The neutrophil alkaline phosphatase score is increased in both conditions and is of no value in making a distinction. PMID:26218186

  9. Evasion of Neutrophil Killing by Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Will A. McGuinness

    2016-03-01

    Full Text Available Staphylococcus aureus causes many types of infections, ranging from self-resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils, are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of the innate immune system and are capable of producing non-specific antimicrobial molecules that are effective at eliminating bacteria. Although significant progress has been made over the past few decades, our knowledge of S. aureus-host innate immune system interactions is incomplete. Most notably, S. aureus has the capacity to produce numerous molecules that are directed to protect the bacterium from neutrophils. Here we review in brief the role played by neutrophils in defense against S. aureus infection, and correspondingly, highlight selected S. aureus molecules that target key neutrophil functions.

  10. Candida albicans escapes from mouse neutrophils

    DEFF Research Database (Denmark)

    Ermert, David; Niemiec, Maria J; Röhm, Marc;

    2013-01-01

    Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse...... 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 that murine neutrophils exhibited a significantly lower ability to kill C. albicans than their human counterparts. Strikingly, C. albicans yeast cells formed germ tubes upon internalization by murine neutrophils, eventually rupturing the neutrophil membrane and thereby, killing the phagocyte. On...

  11. 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.

  12. Inflammatory response and extracorporeal circulation.

    Science.gov (United States)

    Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander

    2015-06-01

    Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery. PMID:26060024

  13. VanderLaan Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Hongyan Pan

    2015-01-01

    Full Text Available Circulant matrices have become a satisfactory tools in control methods for modern complex systems. In the paper, VanderLaan circulant type matrices are presented, which include VanderLaan circulant, left circulant, and g-circulant matrices. The nonsingularity of these special matrices is discussed by the surprising properties of VanderLaan numbers. The exact determinants of VanderLaan circulant type matrices are given by structuring transformation matrices, determinants of well-known tridiagonal matrices, and tridiagonal-like matrices. The explicit inverse matrices of these special matrices are obtained by structuring transformation matrices, inverses of known tridiagonal matrices, and quasi-tridiagonal matrices. Three kinds of norms and lower bound for the spread of VanderLaan circulant and left circulant matrix are given separately. And we gain the spectral norm of VanderLaan g-circulant matrix.

  14. Proliferating cell nuclear antigen in neutrophil fate.

    Science.gov (United States)

    Witko-Sarsat, Véronique; Ohayon, Delphine

    2016-09-01

    The life span of a neutrophil is a tightly regulated process as extended survival is beneficial for pathogen elimination and cell death necessary to prevent cytotoxic content release from activated neutrophils at the inflammatory site. Therefore, the control between survival and death must be a dynamic process. We have previously described that proliferating cell nuclear antigen (PCNA) which is known as a nuclear protein pivotal in DNA synthesis, is a key element in controlling neutrophil survival through its association with procaspases. Contrary to the dogma which asserted that PCNA has a strictly nuclear function, in mature neutrophils, PCNA is present exclusively within the cytosol due to its nuclear export at the end of the granulocytic differentiation. More recent studies are consistent with the notion that the cytosolic scaffold of PCNA is aimed at modulating neutrophil fate rather than simply preventing death. Ultimately, targeting neutrophil survival might have important applications not just in the field of immunology and inflammation, but also in hematology and transfusion. The neutrophil emerges as a unique and powerful cellular model to unravel the basic mechanisms governing the cell cycle-independent functions of PCNA and should be considered as a leader of the pack. PMID:27558345

  15. 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. PMID:27436438

  16. The association of elevated reactive oxygen species levels from neutrophils with low-grade inflammation in the elderly

    Directory of Open Access Journals (Sweden)

    Suzuki Katsuhiko

    2008-10-01

    Full Text Available Abstract Background Reactive oxygen species (ROS, including free radicals, oxygen ions, and peroxides, are implicated in cell damage. The objective of this study was to investigate whether the spontaneous production of ROS from neutrophils changes with age and is associated with the conventional inflammatory markers. Results Thirty-seven elderly subjects (median age, 87, range 70–95 years and 22 young subjects (median age, 26, range 21–37 years participated in this study. Circulating levels of C-reactive protein, serum amyloid A, tumor necrosis factor-α, interleukin (IL-1, IL-6, IL-8, monocyte chemotactic protein-1, and heat shock protein (HSP70 were measured with enzyme-linked immunosorbent assays. The N-formyl-methionyl-leucyl-phenylalanine and lipopolysaccharide-stimulated ROS of neutrophils were quantified by flow cytometry. Both spontaneous ROS production and circulating levels of inflammatory markers were higher in the elderly group than in the younger group. In addition, spontaneous ROS production by neutrophils was negatively associated with HSP70 in plasma. We could not find the association between spontaneous ROS production by neutrophils and the other inflammatory markers including cytokines. Conclusion The results suggest that spontaneous ROS production from neutrophils may increase with age and represent the different aspect of age-associated immune dysregulation.

  17. Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis.

    Science.gov (United States)

    Jiang, Zhao-Xin; Qiu, Suo; Lou, Bing-Sheng; Yang, Yao; Wang, Wen-Cong; Lin, Xiao-Feng

    2016-08-01

    Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin‑induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS‑induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick‑end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription‑quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC‑1 and ICAM‑1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels

  18. Circulation economics

    DEFF Research Database (Denmark)

    Ingebrigtsen, Stig; Jakobsen, Ove

    2006-01-01

    Purpose - This paper is an attempt to advance the critical discussion regarding environmental and societal responsibility in economics and business. Design/methodology/approach - The paper presents and discusses as a holistic, organic perspective enabling innovative solutions to challenges...... concerning the responsible and efficient use of natural resources and the constructive interplay with culture. To reach the goal of sustainable development, the paper argues that it is necessary to make changes in several dimensions in mainstream economics. This change of perspective is called a turn towards...... presupposes a perspective integrating economic, natural and cultural values. Third, to organize the interplay between all stakeholders we introduce an arena for communicative cooperation. Originality/value - The paper concludes that circulation economics presupposes a change in paradigm, from a mechanistic...

  19. DETECTION OF A NEUTROPHIL CHEMOTACTIC FACTOR IN JAPANESE ENCEPHALITIS PATIENTS

    Directory of Open Access Journals (Sweden)

    Aditi Singh

    2012-12-01

    Full Text Available Japanese encephalitis (JE one of the most common cause of acute encephalitis in tropical regions, has generated much public anxiety in India. An early influx of macrophages followed by neutrophils at the site of injury in different organs in humans and mice has previously been reported. It correlated with production of a neutrophil chemotactic protein derived from macrophages. In the present study out of a total of 324 acute encephalitic patients, admitted in Gandhi memorial and associated hospitals, Lucknow, 121 patients with one or more indicators of JE virus infection were included. Significant pleocytosis (mean TLC value of 126+52 cells / mm3 in CSF and leucocytosis (>11,000 cells/mm3 in peripheral blood was observed at the time of admission. The leucocytosis increased significantly during second week in 67% of patients. The peripheral blood mononuclear cells culture done on alternate days was tested for chemotactic activity (hMDF, which was observed to be highest in second week of illness. The direct detection of hMDF in circulation by dot blot was positive in 92% of acute serum samples, with negligible (12.5% reactivity for convalescent sera. A correlation between the hMDF levels and severity of illness has also been observed.

  20. Real-time detection of implant-associated neutrophil responses using a formyl peptide receptor-targeting NIR nanoprobe

    Directory of Open Access Journals (Sweden)

    Zhou J

    2012-05-01

    Full Text Available Jun Zhou*, Yi-Ting Tsai*, Hong Weng, Ewin N Tang, Ashwin Nair, Digant P Davé, Liping Tang, Department of Bioengineering, University of Texas at Arlington, Arlington, TX *Both authors contributed equally to this workAbstract: Neutrophils play an important role in implant-mediated inflammation and infection. Unfortunately, current methods which monitor neutrophil activity, including enzyme measurements and histological evaluation, require many animals and cannot be used to accurately depict the dynamic cellular responses. To understand the neutrophil interactions around implant-mediated inflammation and infection it is critical to develop methods which can monitor in vivo cellular activity in real time. In this study, formyl peptide receptor (FPR-targeting near-infrared nanoprobes were fabricated. This was accomplished by conjugating near-infrared dye with specific peptides having a high affinity to the FPRs present on activated neutrophils. The ability of FPR-targeting nanoprobes to detect and quantify activated neutrophils was assessed both in vitro and in vivo. As expected, FPR-targeting nanoprobes preferentially accumulated on activated neutrophils in vitro. Following transplantation, FPR-targeting nanoprobes preferentially accumulated at the biomaterial implantation site. Equally important, a strong relationship was observed between the extent of fluorescence intensity in vivo and the number of recruited neutrophils at the implantation site. Furthermore, FPR-targeting nanoprobes may be used to detect and quantify the number of neutrophils responding to a catheter-associated infection. The results show that FPR-targeting nanoprobes may serve as a powerful tool to monitor and measure the extent of neutrophil responses to biomaterial implants in vivo.Keywords: in vivo imaging, nanoprobe, neutrophils, inflammation, biocompatibility

  1. ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils

    DEFF Research Database (Denmark)

    Roychaudhuri, Robin; Hergrueter, Anja H; Polverino, Francesca;

    2014-01-01

    A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein is...... stored in the gelatinase and specific granules and the secretory vesicles of human PMNs. Unstimulated PMNs express minimal quantities of surface ADAM9, but activation of PMNs with degranulating agonists rapidly (within 15 min) increases PMN surface ADAM9 levels. Human PMNs produce small quantities of...... soluble forms of ADAM9. Surprisingly, ADAM9 degrades several extracellular matrix (ECM) proteins, including fibronectin, entactin, laminin, and insoluble elastin, as potently as matrix metalloproteinase-9. However, ADAM9 does not degrade types I, III, or IV collagen or denatured collagens in vitro. To...

  2. Anti-neutrophil cytoplasmic antibodies in rheumatoid arthritis: two case reports and review of literature

    Directory of Open Access Journals (Sweden)

    Spoerl David

    2012-12-01

    Full Text Available Abstract Background Anti-neutrophil cytoplasmic antibodies are typically detected in anti-neutrophil cytoplasmic antibody associated vasculitis, but are also present in a number of chronic inflammatory non-vasculitic conditions like rheumatoid arthritis. Rare cases of granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis, a vasculitic disorder frequently associated with the presence of anti-neutrophil cytoplasmic antibodies in patients with rheumatoid arthritis have been described in literature. Case presentation We report two middle-aged female patients with rheumatoid arthritis who developed anti-neutrophil cytoplasmic antibodies and symptoms reminiscent of granulomatosis with polyangiitis. Despite the lack of antibodies specific for proteinase 3 and the absence of a classical histology, we report a probable case of granulomatosis with polyangiitis in the first patient, and consider rheumatoid vasculitis in the second patient. Conclusion Taken together with previous reports, these cases highlight that anti-neutrophil cytoplasmic antibodies have to be evaluated very carefully in patients with rheumatoid arthritis. In this context, anti-neutrophil cytoplasmic antibodies detected by indirect immunofluorescence appear to have a low diagnostic value for granulomatosis with polyangiitis. Instead they may have prognostic value for assessing the course of rheumatoid arthritis.

  3. 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.

  4. 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. PMID:19371737

  5. Moesin regulates neutrophil rolling velocity in vivo.

    Science.gov (United States)

    Matsumoto, Masanori; Hirata, Takako

    2016-01-01

    During inflammation, the selectin-induced slow rolling of neutrophils on venules cooperates with chemokine signaling to mediate neutrophil recruitment into tissues. Previous studies identified P-selectin glycoprotein ligand-1 (PSGL-1) and CD44 as E-selectin ligands that activate integrins to induce slow rolling. We show here that in TNF-α-treated cremaster muscle venules, slow leukocyte rolling was impaired in mice deficient in moesin, a member of the ezrin-radixin-moesin (ERM) family. Accordingly, neutrophil recruitment in a peritonitis model was decreased in moesin-deficient mice when chemokine signaling was blocked with pertussis toxin. These results suggest that moesin contributes to the slow rolling and subsequent recruitment of neutrophils during inflammation. PMID:27131737

  6. MBL-mediated opsonophagocytosis of Candida albicans by human neutrophils is coupled with intracellular Dectin-1-triggered ROS production.

    Directory of Open Access Journals (Sweden)

    Dongsheng Li

    Full Text Available Mannan-binding lectin (MBL, a lectin homologous to C1q, greatly facilitates C3/C4-mediated opsonophagocytosis of Candida albicans (C. albicans by human neutrophils, and has the capacity to bind to CR1 (CD35 expressed on circulating neutrophils. The intracellular pool of neutrophil Dectin-1 plays a critical role in stimulating the reactive oxygen species (ROS generation through recognition of β-1,3-glucan component of phagocytized zymosan or yeasts. However, little is known about whether MBL can mediate the opsonophagocytosis of Candida albicans by neutrophils independent of complement activation, and whether MBL-mediated opsonophagocytosis influence the intracellular expression of Dectin-1 and ROS production. Here we showed that the inhibited phagocytic efficiency of neutrophils as a result of blockage of Dectin-1 was compensated by exogenous MBL alone in a dose-dependent manner. Furthermore, the expressions of Dectin-1 at mRNA and intracellular protein levels were significantly up-regulated in neutrophils stimulated by MBL-pre-incubated C. albicans, while the expression of surface Dectin-1 remained almost unchanged. Nevertheless, the stimulated ROS production in neutrophils was partly and irreversibly inhibited by blockage of Dectin-1 in the presence of exogenous MBL. Confocal microscopy examination showed that intracellular Dectin-1 was recruited and co-distributed with ROS on the surface of some phagocytized yeasts. The β-1,3-glucanase digestion test further suggested that the specific recognition and binding site of human Dectin-1 is just the β-1,3-glucan moiety on the cell wall of C. albicans. These data demonstrate that MBL has an ability to mediate the opsonophagocytosis of Candida albicans by human neutrophils independent of complement activation, which is coupled with intracellular Dectin-1-triggered ROS production.

  7. Neutrophils in asthma--a review.

    Science.gov (United States)

    Ciepiela, Olga; Ostafin, Magdalena; Demkow, Urszula

    2015-04-01

    Asthma is a chronic inflammatory disease, with an array of cells involved in the pathogenesis of the disease. The role of neutrophils in the development of bronchial asthma is found to be complex, as they may trigger activation of immunocompetent cells and are a potent source of free oxygen radicals and enzymes participating in airway remodeling. The review highlights the role of neutrophils in bronchial asthma. PMID:25511380

  8. 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.

  9. Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Lai

    2014-11-01

    Full Text Available Aims: Neutrophils can synthesize leukotriene B4 (LTB4 by activating the 5-lipoxygenase (5-LOsignaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2.

  10. Relationship between AOPP (Advanced Oxidation Protein Products) and bovine neutrophils "in vitro": AOPP production by neutrophils and AOPP effects on neutrophils ROS production and viability

    OpenAIRE

    Bordignon, Milena

    2013-01-01

    The aim of the present study was to evaluate the relationship between AOPP (Advanced oxidation protein products) and bovine neutrophils 'in vitro'. For this purpose AOPP were produced "in vitro" by oxidizing bovine serum albumin with HOCl (hypochlorous acid) and bovine neutrophils were isolated from whole blood of dairy cattles. AOPP-BSA were incubated with freshly isolated bovine neutrophils, unstimulated and stimulated with PMA a strong activator of the respiratory burst. Neutrophils ROS pr...

  11. PEGylated single-walled carbon nanotubes activate neutrophils to increase production of hypochlorous acid, the oxidant capable of degrading nanotubes

    International Nuclear Information System (INIS)

    Perspectives for the use of carbon nanotubes in biomedical applications depend largely on their ability to degrade in the body into products that can be easily cleared out. Carboxylated single-walled carbon nanotubes (c-SWCNTs) were shown to be degraded by oxidants generated by peroxidases in the presence of hydrogen peroxide. In the present study we demonstrated that conjugation of poly(ethylene glycol) (PEG) to c-SWCNTs does not interfere with their degradation by peroxidase/H2O2 system or by hypochlorite. Comparison of different heme-containing proteins for their ability to degrade PEG-SWCNTs has led us to conclude that the myeloperoxidase (MPO) product hypochlorous acid (HOCl) is the major oxidant that may be responsible for biodegradation of PEG-SWCNTs in vivo. MPO is secreted mainly by neutrophils upon activation. We hypothesize that SWCNTs may enhance neutrophil activation and therefore stimulate their own biodegradation due to MPO-generated HOCl. PEG-SWCNTs at concentrations similar to those commonly used in in vivo studies were found to activate isolated human neutrophils to produce HOCl. Both PEG-SWCNTs and c-SWCNTs enhanced HOCl generation from isolated neutrophils upon serum-opsonized zymosan stimulation. Both types of nanotubes were also found to activate neutrophils in whole blood samples. Intraperitoneal injection of a low dose of PEG-SWCNTs into mice induced an increase in percentage of circulating neutrophils and activation of neutrophils and macrophages in the peritoneal cavity, suggesting the evolution of an inflammatory response. Activated neutrophils can produce high local concentrations of HOCl, thereby creating the conditions favorable for degradation of the nanotubes. -- Highlights: ► Myeloperoxidase (MPO) product hypochlorous acid is able to degrade CNTs. ► PEGylated SWCNTs stimulate isolated neutrophils to produce hypochlorous acid. ► SWCNTs are capable of activating neutrophils in blood samples. ► Activation of neutrophils in

  12. 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.

  13. Neutrophils and neutrophil extracellular traps orchestrate initiation and resolution of inflammation.

    Science.gov (United States)

    Hahn, Jonas; Knopf, Jasmin; Maueröder, Christian; Kienhöfer, Deborah; Leppkes, Moritz; Herrmann, Martin

    2016-01-01

    Neutrophils, the most abundant leukocytes in the human body, are considered to be the first line of defense in the fight against microorganisms. In this fight neutrophils employ weaponry such as reactive oxygen species produced via the NADPH oxidase complex 2 together with the release of intracellular granules containing antimicrobial agents. The discovery that activated neutrophils release decondensed chromatin as DNase-sensitive neutrophil extracellular traps (NETs) lead to a renewed interest in these leukocytes and the function of NETs in vivo. In this review, we will focus on desirable as well as detrimental features of NETs by the example of gout and pancreatitis. In our models we observed that neutrophils drive the initiation of inflammation and are required for the resolution of inflammation. PMID:27586795

  14. Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases.

    Directory of Open Access Journals (Sweden)

    Jason S. Knight

    2012-12-01

    Full Text Available Neutrophils are the most abundant leukocytes in circulation and represent one of the first lines of defense against invading pathogens. Neutrophils possess a vast arsenal of antimicrobial proteins, which can be released from the cell by a death program termed NETosis. Neutrophil extracellular traps (NETs are web-like structures consisting of decondensed chromatin decorated with granular and cytosolic proteins. Both exuberant NETosis and impaired clearance of NETs have been implicated in the organ damage of autoimmune diseases, such as systemic lupus erythematosus (SLE, small vessel vasculitis (SVV, and psoriasis. NETs may represent a source of modified autoantigens in SLE and SVV. Here, we review the autoimmune diseases linked to NETosis, with a focus on how modified proteins externalized on the NETs may trigger loss of immune tolerance and promote organ damage.

  15. Enhanced neutrophil migration in vivo HLA B27 positive subjects.

    OpenAIRE

    Koivuranta-Vaara, P; Repo, H; Leirisalo, M; Kiistala, U; Osterman, T; Vapaatalo, H

    1984-01-01

    Chemotaxis of polymorphonuclear leucocytes in vivo was studied in patients with previous yersinia arthritis and in healthy subjects with or without HLA B27 by means of a skin chamber technique. Irrespective of previous arthritis the number of neutrophils in the chamber media was significantly higher in HLA B27 positive subjects than in those without HLA B27. The amounts of prostaglandins E2, F2 alpha, and 6-keto-F1 alpha in the chamber media correlated positively with the corresponding cell c...

  16. Therapeutic Potential of Human Neutrophil Peptide 1 against Experimental Tuberculosis

    OpenAIRE

    Sharma, Sudhir; Verma, Indu; Khuller, G. K.

    2001-01-01

    The therapeutic efficacy of human neutrophil peptide 1 (HNP-1) against experimental tuberculosis in mice on the basis of numbers of CFU has been examined. Mice infected with 1.5 × 104 CFU of Mycobacterium tuberculosis H37Rv and treated with different doses of HNP-1 injected subcutaneously exhibited significant clearance of bacilli from lungs, livers, and spleens. There were time- and dose-dependent decreases in the bacillary load in lungs, livers, and spleens of the HNP-1-treated animals comp...

  17. Neutrophilic and Pauci-immune Phenotypes in Severe Asthma.

    Science.gov (United States)

    Panettieri, Reynold A

    2016-08-01

    Although 2 T-helper type 2 inflammation evokes airway hyperresponsiveness and narrowing, neutrophilic or pauci-immune asthma accounts for significant asthma morbidity. Viruses, toxicants, environmental tobacco smoke exposure, and bacterial infections induce asthma exacerbations mediated by neutrophilic inflammation or by structural cell (pauci-immune) mechanisms. Therapeutic challenges exist in the management of neutrophilic and pauci-immune phenotypes because both syndromes manifest steroid insensitivity. The recognition that neutrophil subsets exist and their functions are unique poses exciting opportunities to develop precise therapies. The conventional thought to target neutrophil activation or migration globally may explain why current drug development in neutrophilic asthma remains challenging. PMID:27401627

  18. Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus.

    Science.gov (United States)

    Saeb-Lima, Marcela; Charli-Joseph, Yann; Rodríguez-Acosta, Elva Dalia; Domínguez-Cherit, Judith

    2013-08-01

    Neutrophilic dermatoses have long been known to be associated with autoinmune systemic diseases. Recently, a small number of cases of a disorder distinct from Sweet syndrome or bullous lupus erythematosus (LE) have been described as specifically related to systemic LE under diverse terms, including nonbullous neutrophilic dermatosis, nonbullous neutrophilic LE, and Sweet-like neutrophilic dermatosis. We describe 7 patients that developed urticarial lesions in the context of a known or concurrently diagnosed autoimmune connective tissue disease. Of a total of 7 patients, 6 were afflicted by systemic LE and 1 by rheumatoid arthritis and secondary Sjögren syndrome. Histological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, vacuolar alteration along the dermal-edidermal junction, and no vasculitis. Most patients had active systemic disease at the time of the cutaneous eruption. Skin lesions resolved rapidly after the administration of immunomodulating agents. In conclusion, we provide additional evidence of the existence of a recently defined nonbullous neutrophilic dermatosis in the context of autoimmune connective tissue diseases and propose the term autoimmunity-related neutrophilic dermatosis as an appropriate designation. Furthermore, we believe that this entity should prompt physicians to screen the presence of an active systemic disorder in afflicted patients. PMID:23518639

  19. Stimulation of neutrophils by tumor necrosis factor

    International Nuclear Information System (INIS)

    Human recombinant tumor necrosis factor (TNF) was shown to be a weak direct stimulus of the neutrophil respiratory burst and degranulation. The stimulation, as measured by iodination, H2O2 production, and lysozyme release, was considerably increased by the presence of unopsonized zymosan in the reaction mixture, an effect which was associated with the increased ingestion of the zymosan. TNF does not act as an opsonin but, rather, reacts with the neutrophil to increase its phagocytic activity. TNF-dependent phagocytosis, as measured indirectly by iodination, is inhibited by monoclonal antibodies (Mab) 60.1 and 60.3, which recognize different epitopes on the C3bi receptor/adherence-promoting surface glycoprotein of neutrophils. Other neutrophil stimulants, namely N-formyl-methionyl-leucyl-phenylalanine, the Ca2+ ionophore A23187, and phorbol myristic acetate, also increase iodination in the presence of zymosan; as with TNF, the effect of these stimulants is inhibited by Mab 60.1 and 60.3, whereas, in contrast to that of TNF, their stimulation of iodination is unaffected by an Mab directed against TNF. TNF may be a natural stimulant of neutrophils which promotes adherence to endothelial cells and to particles, leading to increased phagocytosis, respiratory burst activity, and degranulation

  20. Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst

    Indian Academy of Sciences (India)

    David Alan Thompson; Bruce D Hammock

    2007-03-01

    The leukotoxins [9(10)- and 12(13)-EpOME] are produced by activated inflammatory leukocytes such as neutrophils. High EpOME levels are observed in disorders such as acute respiratory distress syndrome and in patients with extensive burns. Although the physiological significance of the EpOMEs remains poorly understood, in some systems, the EpOMEs act as a protoxin, with their corresponding epoxide hydrolase metabolites, 9,10- and 12,13-DiHOME, specifically exerting toxicity. Both the EpOMEs and the DiHOMEs were also recently shown to have neutrophil chemotactic activity. We evaluated whether the neutrophil respiratory burst, a surge of oxidant production thought to play an important role in limiting certain bacterial and fungal infections, is modulated by members of the EpOME metabolic pathway. We present evidence that the DiHOMEs suppress the neutrophil respiratory burst by a mechanism distinct from that of respiratory burst inhibitors such as cyclosporin H or lipoxin A4, which inhibit multiple aspects of neutrophil activation.

  1. The Inhibitory Effect of Quercetin on IL-6 Production by LPS-Stimulated Neutrophils

    Institute of Scientific and Technical Information of China (English)

    Jiajia Liu; Xin Li; Yang Yue; Juan Li; Tao He; Yanzheng He

    2005-01-01

    Quercetin is a herbal flavonoid derived from various foods of plant origin and plays a role in anti-inflammation. Although a number of researches in the field have been done, the mechanism of anti-inflammatory effect of quercetin should be further clarified. In the present study, we investigated the effects of quercetin on IL-6 production by LPS-stimulated neutrophils in human. Neutrophils were were pre-treated with quercetin at the final concentrations of ranging from 0-80 μM for 30 min, or not treated, and then incubated in the presence or absence of lipopolysaccharide (LPS) at a final concentration of 100 ng/ml for indicated time. The secretion level of IL-6 in the culture supernatants was assayed by ELISA, the intracellular level of IL-6 was detected by flow cytometry and the expression of IL-6 mRNA was analyzed by RT-PCR. The experiment results showed that neutrophils cultured with medium or quercetin alone did not express IL-6, but LPS (100 ng/ml) induced IL-6 expression of neutrophils. However, after pre-treatment of neutrophils with quercetin (40 μM) for 30 min, the inducible effects of LPS on the increase of IL-6 secretion, intracellular IL-6 level and IL-6 mRNA expression by neutrophils were abrogated. IL-6 is one of the important pro-inflammatory factors, especially in early phage of inflammation. Thus, our data suggested that quercetin might exert its anti-inflammatory effect through negatively modulating pro-inflammatory factors, such as IL-6. The inhibitory effects of quercetin on IL-6 production by neutrophils may provide a theoretical basis on future therapy of inflammation.

  2. Granulopoiesis and granules of human neutrophils.

    Science.gov (United States)

    Cowland, Jack B; Borregaard, Niels

    2016-09-01

    Granules are essential for the ability of neutrophils to fulfill their role in innate immunity. Granule membranes contain proteins that react to environmental cues directing neutrophils to sites of infection and initiate generation of bactericidal oxygen species. Granules are densely packed with proteins that contribute to microbial killing when liberated to the phagosome or extracellularly. Granules are, however, highly heterogeneous and are traditionally subdivided into azurophil granules, specific granules, and gelatinase granules in addition to secretory vesicles. This review will address issues pertinent to formation of granules, which is a process intimately connected to maturation of neutrophils from their precursors in the bone marrow. We further discuss possible mechanisms by which decisions are made regarding sorting of proteins to constitutive secretion or storage in granules and how degranulation of granule subsets is regulated. PMID:27558325

  3. 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.

  4. Treatment with anti-RANKL antibody reduces infarct size and attenuates dysfunction impacting on neutrophil-mediated injury.

    Science.gov (United States)

    Carbone, Federico; Crowe, Lindsey A; Roth, Aline; Burger, Fabienne; Lenglet, Sébastien; Braunersreuther, Vincent; Brandt, Karim J; Quercioli, Alessandra; Mach, François; Vallée, Jean-Paul; Montecucco, Fabrizio

    2016-05-01

    Selective pharmacological treatments targeting reperfusion injury produced modest protective effects and might be associated with immunosuppression. In order to identify novel and better-tolerated approaches, we focused on the neutralization of receptor activator of nuclear factor kappa-B ligand [RANKL], a cytokine recently shown to activate inflammatory cells (i.e. neutrophils) orchestrating post-infarction injury and repair. Myocardial ischemia (60min) and reperfusion injury was surgically induced in C57Bl/6 mice. In hearts and serum, RANKL was early upregulated during reperfusion. A "one-shot" injection with neutralizing anti-RANKL IgG during ischemia ameliorated myocardial infarct size and function, but not adverse remodeling (determined by Magnetic Resonance Imaging [MRI]) as compared to Vehicle or control IgG. These beneficial effects were accompanied in vivo by reduction in cardiac neutrophil infiltration, reactive oxygen species (ROS) and MMP-9 release. Anti-RANKL IgG treatment suppressed sudden peak of neutrophil granule products in mouse serum early after reperfusion onset. In vitro, RANK mRNA expression was detected in isolated mouse neutrophils. Co-incubation with neutralizing anti-RANKL IgG abrogated RANKL-induced mouse neutrophil degranulation and migration, suggesting a critical role of RANKL in neutrophil-mediated injury. Conversely, anti-RANKL IgG did not affect salvage pathways in cardiac cells (i.e. ERK p42/p44, Akt and STAT-3) or macrophage cardiac infiltration. Finally, treatment with anti-RANKL IgG showed no effect on B and T lymphocyte polarization (in serum, spleen and infarcted myocardium) and circulating chemokines as compared with Vehicle or control IgG. In conclusion, acute treatment with anti-RANKL IgG improved cardiac infarct size and function by potentially impacting on neutrophil-mediated injury and repair. PMID:27056420

  5. Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Kun Shang

    Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

  6. Anti-neutrophil cytoplasm autoantibodies (ANCA) in autoimmune liver diseases

    NARCIS (Netherlands)

    Roozendaal, C.; Kallenberg, Cees

    1999-01-01

    Anti-neutrophil cytoplasm antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes and monocytes. ANCA have been detected in serum from patients with inflammatory bowel diseases (mainly ulcerative colitis) and autoimmune mediated liver diseases (mainl

  7. Technical advance: Inhibition of neutrophil chemotaxis by colchicine is modulated through viscoelastic properties of subcellular compartments.

    Science.gov (United States)

    Paschke, Stephan; Weidner, Astrid Franziska; Paust, Tobias; Marti, Othmar; Beil, Michael; Ben-Chetrit, Eldad

    2013-11-01

    Colchicine is an efficient drug for the management of inflammatory diseases, such as gouty arthritis and familial Mediterranean fever. It affects neutrophil activity by interfering with the formation of microtubules. To test the hypothesis that therapeutic concentrations of colchicine modulate the mechanical properties of these cells, we applied a combination of biophysical techniques (optical stretching and microrheology) to analyze cellular deformability. The contribution of the subcellular compartments to the regulation of cell mechanics was determined by fitting a multicomponent model of cellular viscoelasticity to time-dependent deformation curves. Neutrophils were found to be less deformable in response to 10 ng/ml colchicine. The model-based analysis of cellular deformation revealed a decrease in cytoplasmatic elasticity and a substantial increase in both elasticity and viscosity of the cell membrane compartment in response to colchicine. These results correlate with a reduced number of cytoplasmatic microtubules and an increase in subcortical actin filaments. The latter finding was confirmed by microrheology and fluorescence microscopy. Neutrophil migration through small pores requiring substantial cellular deformations, but not through large pores, was significantly impaired by colchicine. These data demonstrate that colchicine determines mechanics of neutrophils and, thereby, motility in confined spaces, which is crucial during extravasation of neutrophils in response to inflammatory stimuli. PMID:23901122

  8. Ranitidine improves postoperative monocyte and neutrophil function

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Nielsen, H; Jensen, S; Moesgaard, F

    1994-01-01

    no adjuvant treatment (n = 13). Blood monocyte and neutrophil chemotaxis and chemiluminescence were analyzed before the operation and on postoperative days 1, 3, and 9. RESULTS: Monocyte chemotaxis to C5a in the 13 control patients was significantly decreased on day 1 compared with day 0. Chemotaxis...... chemiluminescence to zymosan insignificantly on day 1 (P < .07 between groups). Five of the 13 control patients developed postoperative infectious complications, which were related to decreased monocyte chemotaxis to C5a and increased neutrophil chemiluminescence to zymosan, compared with noninfected patients. A...

  9. Analysis of Ascorbic Acid in Single Human Neutrophils by Electrochemical Detection

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Ascorbic acid in individual human neutrophils was determined by capillary zone electrophoresis with electrochemical detection. In order to overcome the influence of the adsorption of the substances in cells on the inner surface wall of the capillary on the migration time and the number of theoretical plates, a procedure for treating capillaries has been described.

  10. Dynamics of neutrophil migration in lymph nodes during infection

    OpenAIRE

    Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; van Dooren, Giel G.; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin; Aaron, Holly; Striepen, Boris; Robey, Ellen A.

    2008-01-01

    While the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes, or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning laser microscopy (TPSLM) to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We find that neutrophils form bo...

  11. Neutrophil extracellular traps: Their role in periodontal disease

    OpenAIRE

    Kolaparthy, Lakshmi Kanth.; Sanivarapu, Sahitya; Swarna, Chakrapani; Devulapalli, Narasimha Swamy

    2014-01-01

    Neutrophils are the first line of innate immune defense against infectious diseases. Since their discovery, they have always been considered tissue-destructive cells responsible for inflammatory tissue damage occurring during infections. Extensive research in the field of neutrophil cell biology and their role skewing the immune response in various infections or inflammatory disorders revealed their importance in the regulation of immune response. Neutrophils also release neutrophil extracell...

  12. Resolvability in Circulant Graphs

    Institute of Scientific and Technical Information of China (English)

    Muhammad SALMAN; Imran JAVAID; Muhammad Anwar CHAUDHRY

    2012-01-01

    A set W of the vertices of a connected graph G is called a resolving set for G if for every two distinct vertices u,v ∈ V(G) there is a vertex w ∈ W such that d(u,w) ≠ d(v,w).A resolving set of minimum cardinality is called a metric basis for G and the number of vertices in a metric basis is called the metric dimension of G,denoted by dim(G).For a vertex u of G and a subset S of V(G),the distance between u and S is the number mins∈s d(u,s).A k-partition H ={S1,S2,...,Sk} of V(G) is called a resolving partition if for every two distinct vertices u,v ∈ V(G) there is a set Si in Π such that d(u,Si) ≠ d(v,Si).The minimum k for which there is a resolving k-partition of V(G) is called the partition dimension of G,denoted by pd(G).The circulant graph is a graph with vertex set Zn,an additive group ofintegers modulo n,and two vertices labeled i and j adjacent if and only if i - j (mod n) ∈ C,where C C Zn has the property that C =-C and 0(∈) C.The circulant graph is denoted by Xn,△ where A =|C|.In this paper,we study the metric dimension of a family of circulant graphs Xn,3 with connection set C ={1,-n/2,n - 1} and prove that dim(Xn,3) is independent of choice of n by showing that 3 for all n =0 (mod 4),dim(X,n,3) ={ 4 for all n =2 (mod 4).We also study the partition dimension of a family of circulant graphs Xn,4 with connection set C ={±1,±2} and prove that pd(Xn,4) is independent of choice of n and show that pd(X5,4) =5 and 3 forall odd n≥9,pd(Xn,4) ={ 4 for all even n ≥ 6 and n =7.

  13. Migration of canine neutrophils to chitin and chitosan.

    Science.gov (United States)

    Usami, Y; Okamoto, Y; Minami, S; Matsuhashi, A; Kumazawa, N H; Tanioka, S; Shigemasa, Y

    1994-12-01

    Suspension of chitin and chitosan particles (mean size of 1 micron) were found to attract canine neutrophils chemotactically as determined by a checkerboard assay through polycarbonate filter with 5 microns pore size in Blind well chamber. Suspension of chitin induced chemokinetic migrations of the neutrophils. These evidences might reflect accumulation of neutrophils to chitin- and chitosan-implanted regions in dogs. PMID:7696425

  14. Reciprocal regulation of development of neutrophil-dendritic cell hybrids in mice by IL-4 and interferon-gamma.

    Directory of Open Access Journals (Sweden)

    Shuo Geng

    Full Text Available Neutrophils contribute to innate host immunity by functioning as professional phagocytes, whereas dendritic cells (DCs are prototypic antigen presenting cells (APCs responsible for the induction of adaptive immune responses. We have demonstrated recently that neutrophils trans-differentiate into a unique population, termed "neutrophil-DC hybrids," expressing surface markers of both neutrophils and DCs and exhibiting dual functionality of both phagocytes and APCs. Although the hybrid cells emerged in significant numbers in murine bone marrow (BM culture in the presence of GM-CSF, mechanisms regulating their development remained mostly unknown. In this study, we tested a total of 61 cytokines for their potentials to regulate neutrophil-DC hybrid formation using a newly developed BM micro-culture system combined with semi-automated FACS analysis. Several cytokines including GM-CSF were found to promote the generation of neutrophil-DC hybrids defined by the phenotype of CD11c(+/MHC II(+/Ly6G(+. When tested in the presence of GM-CSF, hybrid cell development was enhanced by IL-4 and suppressed by interferon-γ (IFNγ in dose-dependent fashions. We next determined in vivo impacts of IL-4 and IFNγ on the development of neutrophil-DC hybrids in thioglycollate-induced peritonitis lesions. Intraperitoneal administrations of IL-4/anti-IL-4 antibody complex (IL-4C significantly increased the number of hybrids recovered from the lesions. By contract, recovery of hybrids was reduced by recombinant IFNγ. With regard to function, those hybrid cells recovered from IL-4C-treated mice and IFNγ-treated mice showed potent abilities to capture E.coli. These observations imply that emergence of neutrophil-DC hybrids in inflammatory sites is tightly regulated by local cytokine milieus.

  15. Neutrophilic dermatoses and inflammatory bowel diseases.

    Science.gov (United States)

    Marzano, A V; Menicanti, C; Crosti, C; Trevisan, V

    2013-04-01

    Pyoderma gangrenosum (PG) and Sweet's Syndrome (SS) are inflammatory skin diseases caused by the accumulation of neutrophils in the skin and, rarely, in internal organs, which led to coining the term of neutrophilic dermatoses (ND) to define these conditions. Recently, ND have been included among the autoinflammatory diseases, which are forms due to mutations of genes regulating the innate immune responses. Both PG and SS are frequently associated with inflammatory bowel diseases (IBD), a group of chronic intestinal disorders which comprises ulcerative colitis and Crohn's disease and whose pathogenesis involves both the innate and adaptive immunity in genetically prone individuals. Patients with IBD develop PG in 1-3% of cases, while SS is rarer. PG presents with deep erythematous-to-violaceous painful ulcers with undermined borders, but bullous, pustular, and vegetative variants can also occur. SS, also known as acute febrile neutrophilic dermatosis, is characterized by the abrupt onset of fever, peripheral neutrophilia, tender erythematous skin lesions and a diffuse neutrophilic dermal infiltrate. In this review that will be focused on PG and SS, we will describe also the aseptic abscesses syndrome, a new entity within the spectrum of ND which frequently occurs in association with IBD and is characterized by deep abscesses mainly involving the spleen and skin and by polymorphic cutaneous manifestations including PG- and SS-like lesions. PMID:23588144

  16. Wegener's granulomatosis and autoantibodies to neutrophil antigens

    OpenAIRE

    McCluskey, D R; Maxwell, A. P.; Watt, L

    1988-01-01

    We report five cases of Wegener's granulomatosis all of whom had clinical and histological evidence of disease activity at presentation and in whom autoantibodies to neutrophil antigens were detected. This test may prove useful for the diagnosis of this serious condition and help to monitor disease activity during treatment.

  17. Radiation-induced muscositis and neutrophil granulocytes in oral mucosa

    International Nuclear Information System (INIS)

    Background: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. Patients and Methods: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. Results: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. Conclusions: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated. (orig.)

  18. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2011-04-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  19. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2012-02-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  20. Neutrophil extracellular traps: Their role in periodontal disease.

    Science.gov (United States)

    Kolaparthy, Lakshmi Kanth; Sanivarapu, Sahitya; Swarna, Chakrapani; Devulapalli, Narasimha Swamy

    2014-01-01

    Neutrophils are the first line of innate immune defense against infectious diseases. Since their discovery, they have always been considered tissue-destructive cells responsible for inflammatory tissue damage occurring during infections. Extensive research in the field of neutrophil cell biology and their role skewing the immune response in various infections or inflammatory disorders revealed their importance in the regulation of immune response. Neutrophils also release neutrophil extracellular traps (NETs) for the containment of infection and inflammation along with other antimicrobial molecules. Activated neutrophils provide signals for the activation and maturation of macrophages as well as dendritic cells. Neutrophils are also involved in the regulation of T-cell immune response against various pathogens and tumor antigens. Thus, the present review is intended to highlight the emerging role of neutrophil extracellular trap production in the regulation of immune response and its role in periodontal disease. PMID:25624623

  1. SEXUAL DIMORPHISM IN MORPHOLOGY AND MORPHOMETRY OF NEUTROPHIL DRUMSTICKS

    Directory of Open Access Journals (Sweden)

    Sharmila Tupakula

    2014-12-01

    Full Text Available Introduction: Sex chromatin is a chromatin mass of 1 micron size usually seen at the periphery of nucleus in females. In the literature majority reported its absence in males while few reported its low incidence in males. The term ‘sex chromatin’ comprises two superficially dissimilar structures the “Barr body” present in epithelial and other tissue cells and the “Drumstick” of the polymorphonuclear leucocytes. Materials and methods: The present study was conducted to observe the morphology, morphometry and percentage incidence of Drumsticks in the blood neutrophils of 110 individuals ranging from 17-30 age group and both sexes using a calibrated ocular/eye piece micrometer. Results: The percentage incidence of drumsticks including non-specific appendages as well as the total number of true drumsticks in females exceeds that in males. Four different types of nonspecific appendages-sessile nodules, racket structures, minor lobes and small clubs were found in the blood neutrophils along with the drumsticks. A higher percentage of non-specific appendages i.e. minor lobes (46.2%, racket structures (42.3%, and small clubs (11.5% were observed in males and sessile nodules were found only in females. Conclusion: Observations on morphology, morphometry and percentage incidence of polymorphonuclear drumsticks presented a valuable data on sex differences.

  2. Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

    LENUS (Irish Health Repository)

    Condron, Claire

    2010-08-01

    Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl\\/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g\\/70 kg taurine in 0.9% normal saline (N\\/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.

  3. Circulating Fibronectin Controls Tumor Growth

    Directory of Open Access Journals (Sweden)

    Anja von Au

    2013-08-01

    Full Text Available Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.

  4. An endothelial laminin isoform, laminin 8 (alpha4beta1gamma1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis.

    Science.gov (United States)

    Wondimu, Zenebech; Geberhiwot, Tarekegn; Ingerpuu, Sulev; Juronen, Erkki; Xie, Xun; Lindbom, Lennart; Doi, Masayuki; Kortesmaa, Jarkko; Thyboll, Jill; Tryggvason, Karl; Fadeel, Bengt; Patarroyo, Manuel

    2004-09-15

    During extravasation, neutrophils migrate through the perivascular basement membrane (BM), a specialized extracellular matrix rich in laminins. Laminins 8 (LN-8) (alpha4beta1gamma1) and 10 (LN-10) (alpha5beta1gamma1) are major components of the endothelial BM, but expression, recognition, and use of these laminin isoforms by neutrophils are poorly understood. In the present study, we provide evidence, using a panel of novel monoclonal antibodies against human laminin alpha4 (LNalpha4) chain, that neutrophils contain and secrete LN-8, and that this endogenous laminin contributes to chemoattractant-induced, alphaMbeta2-integrin-dependent neutrophil migration through albumin-coated filters. Phorbol ester-stimulated neutrophils adhered to recombinant human (rh) LN-8, rhLN-10, and mouse LN-1 (mLN-1) (alpha1beta1gamma1) via alphaMbeta2-integrin, and these laminin isoforms strongly promoted chemoattractant-induced neutrophil migration via the same integrin. However, only rhLN-8 enhanced the spontaneous migration. In addition, recruitment of neutrophils into the peritoneum following an inflammatory stimulus was impaired in LNalpha4-deficient mice. rhLN-8 also protected isolated neutrophils from spontaneous apoptosis. This study is the first to identify a specific laminin isoform in neutrophils and provides evidence for the role of LN-8 in the adhesion, migration, extravasation, and survival of these cells. PMID:15172971

  5. Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States.

    Science.gov (United States)

    Fine, N; Hassanpour, S; Borenstein, A; Sima, C; Oveisi, M; Scholey, J; Cherney, D; Glogauer, M

    2016-07-01

    Neutrophils exit the vasculature and swarm to sites of inflammation and infection. However, these cells are abundant in the healthy, inflammation-free human oral environment, suggesting a unique immune surveillance role within the periodontium. We hypothesize that neutrophils in the healthy oral cavity occur in an intermediary parainflammatory state that allows them to interact with and contain the oral microflora without eliciting a marked inflammatory response. Based on a high-throughput screen of neutrophil CD (cluster of differentiation) marker expression and a thorough literature review, we developed multicolor flow cytometry panels to determine the surface marker signatures of oral neutrophil subsets in periodontal health and disease. We define here 3 distinct neutrophil subsets: resting/naive circulatory neutrophils, parainflammatory neutrophils found in the healthy oral cavity, and proinflammatory neutrophils found in the oral cavity during chronic periodontal disease. Furthermore, parainflammatory neutrophils manifest as 2 distinct subpopulations-based on size, granularity, and expression of specific CD markers-and exhibit intermediate levels of activation as compared with the proinflammatory oral neutrophils. These intermediately activated parainflammatory populations occur in equal proportions in the healthy oral cavity, with a shift to one highly activated proinflammatory neutrophil population in chronic periodontal disease. This work is the first to identify and characterize oral parainflammatory neutrophils that interact with commensal biofilms without inducing an inflammatory response, thereby demonstrating that not all neutrophils trafficking through periodontal tissues are fully activated. In addition to establishing possible diagnostic and treatment monitoring biomarkers, this oral neutrophil phenotype model builds on existing literature suggesting that the healthy periodontium may be in a parainflammatory state. PMID:27270666

  6. Treadmill exercise induces neutrophil recruitment into muscle tissue in a reactive oxygen species-dependent manner. An intravital microscopy study.

    Directory of Open Access Journals (Sweden)

    Albená Nunes-Silva

    Full Text Available Intense exercise is a physiological stress capable of inducing the interaction of neutrophils with muscle endothelial cells and their transmigration into tissue. Mechanisms driving this physiological inflammatory response are not known. Here, we investigate whether production of reactive oxygen species is relevant for neutrophil interaction with endothelial cells and recruitment into the quadriceps muscle in mice subjected to the treadmill fatiguing exercise protocol. Mice exercised until fatigue by running for 56.3±6.8 min on an electric treadmill. Skeletal muscle was evaluated by intravital microscopy at different time points after exercise, and then removed to assess local oxidative stress and histopathological analysis. We observed an increase in plasma lactate and creatine kinase (CK concentrations after exercise. The numbers of monocytes, neutrophils, and lymphocytes in blood increased 12 and 24 hours after the exercise. Numbers of rolling and adherent leukocytes increased 3, 6, 12, and 24 hours post-exercise, as assessed by intravital microscopy. Using LysM-eGFP mice and confocal intravital microscopy technology, we show that the number of transmigrating neutrophils increased 12 hours post-exercise. Mutant gp91phox-/- (non-functional NADPH oxidase mice and mice treated with apocynin showed diminished neutrophil recruitment. SOD treatment promoted further adhesion and transmigration of leukocytes 12 hours after the exercise. These findings confirm our hypothesis that treadmill exercise increases the recruitment of leukocytes to the postcapillary venules, and NADPH oxidase-induced ROS plays an important role in this process.

  7. Role of neutrophilic inflammation in ozone-induced epithelial alterations in the nasal airways of rats

    Science.gov (United States)

    Cho, Hye Youn

    Ozone is a principal oxidant air pollutant in photochemical smog. Epithelial cells lining the centriacinar region of lung and the proximal aspects of nasal passage are primary target sites for ozone-induced injury in laboratory animals. Acute exposure of rats to high ambient concentrations of ozone (e.g., 0.5 ppm) results in neutrophilic inflammation, epithelial hyperplasia and mucous cell metaplasia (MCM) in the nasal transitional epithelium (NTE) lining the proximal nasal airways. The principal purpose of the present study was to investigate the role of pre-metaplastic cellular responses, especially neutrophilic inflammation, in the pathogenesis of ozone-induced MCM in rat NTE. For this purpose, three specific hypotheses-based whole-animal inhalation studies were conducted. Male F344/N rats were exposed in whole-body inhalation chambers to 0 (filtered air) or 0.5 ppm ozone for 1-3 days (8 h/day). Histochemical, immunochemical, molecular and morphometric techniques were used to investigate the ozone-induced cellular and molecular events in the NTE. Two in vitro studies were also conducted to examine the effects of ozone-inducible cytokines (i.e., tumor necrosis factor-alpha; TNF- a, and interleukin-6; IL-6) on mucin gene (rMuc-5AC) expression. Ozone induced a rapid increase of rMuc-5AC mRNA in nasal tissues within hours after the start of exposure. It preceded the appearance of MCM, and persisted with MCM. Ozone-induced neutrophilic inflammation accompanied the mucin gene upregulation, but was resolved when MCM first appeared in the NTE. Antibody-mediated depletion of circulating neutrophils attenuated ozone-induced MCM, although it did not affect the ozone-induced epithelial hyperplasia and mucin mRNA upregulation. In another study, it was found that preexisting neutrophilic rhinitis induced by endotoxin augmented the ozone-induced MCM. However, pre-existing rhinitis did not alter the severity of ozone-induced epithelial hyperplasia and mucin gene upregulation

  8. Inflammatory Effects Of Phthalates In Neonatal Neutrophils

    OpenAIRE

    Vetrano, Anna M; Laskin, Debra L.; Archer, Faith; Syed, Kirin; Joshua P Gray; Laskin, Jeffrey D.; Nwebube, Nkiru; Weinberger, Barry

    2010-01-01

    Hospitalized infants are exposed to numerous devices containing the plasticizer di-(2-ethylhexyl) phthalate. Urinary levels of the phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are markedly elevated in premature infants. Phthalates inactivate PPAR-γ, a nuclear transcription factor that mediates the resolution of inflammation, a process impaired in neonates. We speculate that this increases their susceptibility to MEHP, and this was analyzed. MEHP inhibited neutrophil apoptosis; ...

  9. Rat Neutrophils Prevent the Development of Tuberculosis

    OpenAIRE

    Sugawara, Isamu; Udagawa, Tadashi; Yamada, Hiroyuki

    2004-01-01

    To understand the role of neutrophils in the development of rat tuberculosis in vivo, we utilized lipopolysaccharide (LPS)-induced neutrophilia in the lungs. LPS (50 μg/ml) was administered intratracheally to male Fischer rats. Rats were then infected with Mycobacterium tuberculosis by an airborne route. Intratracheal injection of LPS significantly blocked the development of pulmonary granulomas and significantly reduced pulmonary CFU (P < 0.01). LPS treatment with amphotericin B (an LPS inhi...

  10. Neutrophil activator of matrix metalloproteinase-2 (NAM).

    Science.gov (United States)

    Rollo, Ellen E; Hymowitz, Michelle; Schmidt, Cathleen E; Montana, Steve; Foda, Hussein; Zucker, Stanley

    2006-01-01

    We have isolated a novel soluble factor(s), neutrophil activator of matrix metalloproteinases (NAM), secreted by unstimulated normal human peripheral blood neutrophils that causes the activation of cell secreted promatrix metalloproteinase-2 (proMMP-2). Partially purified preparations of NAM have been isolated from the conditioned media of neutrophils employing gelatin-Sepharose chromatography and differential membrane filter centrifugation. NAM activity, as assessed by exposing primary human umbilical vein endothelial cells (HUVEC) or HT1080 cells to NAM followed by gelatin zymography, was seen within one hour. Tissue inhibitor of metalloproteinase-2 (TIMP-2) and hydroxamic acid derived inhibitors of MMPs (CT1746 and BB94) abrogated the activation of proMMP-2 by NAM, while inhibitors of serine and cysteine proteases showed no effect. NAM also produced an increase in TIMP-2 binding to HUVEC and HT1080 cell surfaces that was inhibited by TIMP-2, CT1746, and BB94. Time-dependent increases in MT1-MMP protein and mRNA were seen following the addition of NAM to cells. These data support a role for NAM in cancer dissemination. PMID:17086359

  11. Effect of phenolic acids of microbial origin on production of reactive oxygen species in mitochondria and neutrophils

    Directory of Open Access Journals (Sweden)

    Beloborodova Natalia

    2012-10-01

    Full Text Available Abstract Background Several low-molecular-weight phenolic acids are present in the blood of septic patients at high levels. The microbial origin of the most of phenolic acids in the human body was shown previously, but pathophysiological role of the phenolic acids is not clear. Sepsis is associated with the excessive production of reactive oxygen species (ROS in both the circulation and the affected organs. In this work the influence of phenolic acids on ROS production in mitochondria and neutrophils was investigated. Methods ROS production in mitochondria and neutrophils was determined by MCLA- and luminol-dependent chemiluminescence. The rate of oxygen consumption by mitochondria was determined polarographically. The difference of electric potentials on the inner mitochondrial membrane was registered using a TPP+-selective electrode. The formation of phenolic metabolites in monocultures by the members of the main groups of the anaerobic human microflora and aerobic pathogenic bacteria was investigated by the method of gas chromatography–mass spectrometry. Results All phenolic acids had impact on mitochondria and neutrophils, the main producers of ROS in tissues and circulation. Phenolic acids (benzoic and cinnamic acids producing the pro-oxidant effect on mitochondria inhibited ROS formation in neutrophils. Their effect on mitochondria was abolished by dithiothreitol (DTT. Phenyllactate and p-hydroxyphenyllactate decreased ROS production in both mitochondria and neutrophils. Bifidobacteria and lactobacilli produced in vitro considerable amounts of phenyllactic and p-hydroxyphenyllactic acids, Clostridia s. produced great quantities of phenylpropionic and p-hydroxyphenylpropionic acids, p-hydroxyphenylacetic acid was produced by Pseudomonas aeruginosa and Acinetobacter baumanii; and benzoic acid, by Serratia marcescens. Conclusions The most potent activators of ROS production in mitochondria are phenolic acids whose effect is mediated via the

  12. Diagnosis of autoimmune neutropenia by neutrophil-bound IgG and IgM antibodies.

    Science.gov (United States)

    Ito, Taichi; Taniuchi, Shoichiro; Tsuji, Shoji; Iharada, Anna; Hasui, Masafumi; Kaneko, Kazunari

    2011-10-01

    Autoimmune neutropenia (AIN) in infancy is caused by antineutrophil (granulocyte-specific) autoantibodies. These antibodies are rarely found in circulation because their serum levels are extremely low. We hypothesized that a direct granulocyte immunofluorescence test (D-GIFT) that enables us to detect neutrophil-bound autoantibodies consisting of both immunoglobulin (Ig) G and IgM has better diagnostic value than the detection of circulating autoantibodies. Whole blood (100 μL) was obtained from 50 infants with AIN, 12 infants with transient neutropenia, and 37 control infants. D-GIFT was performed using both fluorescein isothiocyanate-conjugated antihuman IgG Fc portion monoclonal antibodies and fluorescein isothiocyanate antihuman IgM monoclonal antibodies. Results were assessed as relative fluorescence intensity (RFI). The RFIs of antineutrophil IgG-bound and antineutrophil IgM-bound cells in patients with AIN were significantly higher than those in patients with transient neutropenia and in controls. Positive results, as assessed by RFI scores of more than 1.81 in either antineutrophil IgG-bound or antineutrophil IgM-bound cells, showed the sensitivity and specificity of D-GIFT, and the areas under the receiver operating characteristic curve (0.98, 0.98, and 0.997, respectively) in the diagnosis of AIN. D-GIFT detecting both neutrophil-bound IgG autoantibodies and IgM autoantibodies has discriminatory power for identifying patients with AIN and, therefore, can be a useful diagnostic test. PMID:21941149

  13. In the eye of the neutrophil swarm-navigation signals that bring neutrophils together in inflamed and infected tissues.

    Science.gov (United States)

    Lämmermann, Tim

    2016-07-01

    Neutrophils are sentinel cells that express in higher vertebrates >30 chemokine and chemoattractant receptors to sense and quickly react to tissue damage signals. Intravital microscopy studies in mouse models of wounding, inflammation, and infection have revealed that neutrophils form cell swarms at local sites of tissue injury and cell death. This swarming response is choreographed by chemokines, lipids, and other chemoattractants, controlling sequential phases of highly coordinated chemotaxis, intercellular signal relay, and cluster formation among neutrophils. This review will give a brief overview about the basic principles and key molecules that have led to the refined multistep model of how neutrophils come together to isolate sites of tissue injury and microbial invasion from healthy tissue. Whereas auto- and paracrine signaling among neutrophils during later phases of swarming can provide a level of self-organization for robust navigation in diverse inflammatory settings, guidance factors from primary tissue lesions, resident bystander cells, and dying cells regulate the initial phases of the swarming response. This review will discuss how the specific environmental context and mixture of attractants at the locally inflamed site can lead to variants of the multistep attraction model and influence the extent of neutrophil swarming, ranging from accumulations of only few individual cells to the aggregation of several hundreds of neutrophils, as found in abscesses. Given the critical roles of neutrophils in both host protection and tissue destruction, novel insights on neutrophil swarming might provide useful for the therapeutic modulation of neutrophil-dependent inflammatory processes. PMID:26416718

  14. Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives.

    Science.gov (United States)

    Lahoz-Beneytez, Julio; Elemans, Marjet; Zhang, Yan; Ahmed, Raya; Salam, Arafa; Block, Michael; Niederalt, Christoph; Asquith, Becca; Macallan, Derek

    2016-06-30

    Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4 to 18 hours. This dogma was recently challenged by stable isotope labeling studies with heavy water, which yielded estimates in excess of 3 days. To investigate this disparity, we generated new stable isotope labeling data in healthy adult subjects using both heavy water (n = 4) and deuterium-labeled glucose (n = 9), a compound with more rapid labeling kinetics. To interpret results, we developed a novel mechanistic model and applied it to previously published (n = 5) and newly generated data. We initially constrained the ratio of the blood neutrophil pool to the marrow precursor pool (ratio = 0.26; from published values). Analysis of heavy water data sets yielded turnover rates consistent with a short blood half-life, but parameters, particularly marrow transit time, were poorly defined. Analysis of glucose-labeling data yielded more precise estimates of half-life (0.79 ± 0.25 days; 19 hours) and marrow transit time (5.80 ± 0.42 days). Substitution of this marrow transit time in the heavy water analysis gave a better-defined blood half-life of 0.77 ± 0.14 days (18.5 hours), close to glucose-derived values. Allowing the ratio of blood neutrophils to mitotic neutrophil precursors (R) to vary yielded a best-fit value of 0.19. Reanalysis of the previously published model and data also revealed the origin of their long estimates for neutrophil half-life: an implicit assumption that R is very large, which is physiologically untenable. We conclude that stable isotope labeling in healthy humans is consistent with a blood neutrophil half-life of less than 1 day. PMID:27136946

  15. Neutrophils and macrophages: The main partners of phagocyte cell systems

    Directory of Open Access Journals (Sweden)

    Manuel T. Silva

    2012-07-01

    Full Text Available Biological cellular systems are groups of cells sharing a set of characteristics, mainly key function and origin. Phagocytes are crucial in the host defense against microbial infection. The previously proposed phagocyte cell systems including the most recent and presently prevailing one, the Mononuclear Phagocyte System (MPS, grouped mononuclear cells but excluded neutrophils, creating an unacceptable situation. As neutrophils are archetypical phagocytes that must be members of comprehensive phagocyte systems, M. T. Silva recently proposed the creation of a Myeloid Phagocyte System (MYPS that adds neutrophils to the MPS. The phagocytes grouped in the MYPS include the leukocytes neutrophils, inflammatory monocytes, macrophages and immature myeloid DCs. Here the justifications behind the inclusion of neutrophils in a phagocyte system is expanded and the MYPS are further characterized as a group of dedicated phagocytic cells that function in an interacting and cooperative way in the host defense against microbial infection. Neutrophils and macrophages are considered the main arms of this system.

  16. Evaluation of Leukocytes and Neutrophils, Markers of Inflammatory Syndrome in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Andrei MĂLUŢAN

    2010-09-01

    Full Text Available Introduction: In pregnancies with preeclampsia, there is a generalized inflammatory response, which is much more intense than in normal pregnancy. Aim: To evaluate leukocytes and neutrophils in the serum of pregnant women with preeclampsia and to compare these values to normal pregnancy. To investigate a possible relation between the detected values and the severity of preeclamptic syndrome. Material and method: A transversal study was performed in three groups of patients: group 1 (preeclampsia, group 2 (normal pregnancy, group 3 (control. The samples were processed using a multichannel automated hematology analyzer – ACCOS 319. The results obtained were processed by descriptive and comparative statistical methods. Results: A significant increase in leukocyte and neutrophil values was found in preeclampsia compared to normal pregnancy. Also, for group 2 (PE, there was no correlation between the number of leukocytes, neutrophils, respectively, and SBP and uric acid values, but a significant correlation was found between the studied inflammatory markers and DBP values. Conclusions: Leukocyte and neutrophil values can be considered markers of the inflammatory syndrome present in preeclampsia. These parameters were positively correlated with DBP values.

  17. In search of neutrophil granule proteins of the tammar wallaby (Macropus eugenii).

    Science.gov (United States)

    Ambatipudi, Kiran; Deane, Elizabeth M

    2008-02-01

    Two approaches have been used to isolate and identify proteins of the granules of neutrophils of the tammar wallaby, Macropus eugenii. Stimulation with PMA, Ionomycin and calcium resulted in exocytosis of neutrophil granules as demonstrated with electron microscopy. However proteomic analysis using two dimensional gel electrophoresis, in-gel trypsin digestion followed by nano liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) failed to identify any anticipated granule proteins in the reaction supernatants. Subsequent use of differential centrifugation and lysis followed by the application of the same proteomic analysis approach resulted in the isolation and confident identification of 39 proteins, many of which are known to be present in the granules of neutrophils of eutherian mammals or play a role in degranulation. These proteins notably consisted of the known antimicrobials, myeloperoxidase (MPO), serine proteinase, dermcidin, lysozyme and alkaline phosphatase. A number of important known antimicrobials, however, were not detected and these include defensins and cathelicidins. This is the first report of the neutrophil granule proteins of any marsupial and complements previous reports on the cytosolic proteins. PMID:17706783

  18. Purchase, circulation and fuel taxation

    OpenAIRE

    Potter, Stephen

    2008-01-01

    During the last decade, the UK and many other developed nations have reformed existing forms of road transport taxation to address a number of transport policy goals. This has involved modifying the design of purchase, circulation and fuel taxation to promote: • More fuel efficient vehicles • Alternative fuel vehicles • Cleaner fuels (lower emissions and/or low carbon) • Modal shift and traffic volume • Congestion reduction This chapter particularly explores the use of...

  19. Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis.

    OpenAIRE

    Jennette, J C; Wilkman, A. S.; Falk, R J

    1989-01-01

    Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patient...

  20. Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma

    OpenAIRE

    Girolamo Pelaia; Alessandro Vatrella; Maria Teresa Busceti; Luca Gallelli; Cecilia Calabrese; Rosa Terracciano; Rosario Maselli

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes un...

  1. Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants

    OpenAIRE

    Weinberger, Barry; Laskin, Debra L.; Mariano, Thomas M.; Sunil, Vasanthi R.; DeCoste, Christina J.; Heck, Diane E.; Carol R. Gardner; Laskin, Jeffrey D.

    2001-01-01

    Potential mechanisms underlying impaired chemotactic responsiveness of neonatal neutrophils were investigated. Two distinct chemoattractants were compared: bacterially derived N-formyl-methionyl-leucyl-phenylalanine (fMLP) and a unique chemotactic monoclonal antibody, designated DL1.2, which binds to a neutrophil antigen with an apparent molecular mass of 120 kDa. Chemotaxis of neutrophils toward fMLP, as well as DL1.2, was reduced in neonates when compared with adult cells. This did not appe...

  2. Phagocytosing human neutrophils inactivate their own granular enzymes.

    OpenAIRE

    Voetman, A A; Weening, R S; Hamers, M N; Meerhof, L J; Bot, A A; Roos, D.

    1981-01-01

    During phagocytosis, neutrophils generate reactive oxygen metabolites and release lysosomal enzymes into the extracellular medium. We have investigated the possibility that these enzyme are inactivated by the oxygen compounds. Phagocytosing neutrophils from 12 patients with chronic granulomatous disease, which do not generate these oxygen metabolites, released two to three times more activity of lysozyme and beta-glucuronidase than did normal neutrophils. This difference proved to be due to a...

  3. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    OpenAIRE

    Ritankar Majumdar; Aidin Tavakoli Tameh; Carole A Parent

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4...

  4. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

    OpenAIRE

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Carole A Parent

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4...

  5. Rapid Diagnostic Device for Subclinical Mastitis Based on Electrochemical Detection of Superoxide Produced from Neutrophils in Fresh Milk

    Science.gov (United States)

    Okada, Kohei; Fukuda, Junji; Suzuki, Hiroaki

    Electrochemical microdevices were fabricated to identify mastitic cows based on the increased number of neutrophils in raw milk. Because neutrophils produce superoxide (O2·-), the amount of O2·- can be used as an early indicator for subclinical mastitis. In the microdevices, O2·- was detected on a gold electrode using superoxide dismutase immobilized via a self-assembled monolayer of cysteine. In a preliminary test using xanthine oxidase to produce O2·-, one of the devices detected the production and rapid extinction of O2·-. When neutrophils obtained from a mastitic cow were concentrated by centrifugation and introduced into the device, a current increase distinctly different from the background was observed. Furthermore, a micropillar structure was fabricated on the gold electrode to trap and collect neutrophils, thereby facilitating the concentration of these cells around the electrode. The measured current clearly depended on the number of neutrophils in raw milk samples, demonstrating the applicability of the device for rapid diagnosis of subclinical mastitis.

  6. Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

    Science.gov (United States)

    Tamarozzi, F; Wright, H L; Johnston, K L; Edwards, S W; Turner, J D; Taylor, M J

    2014-10-01

    The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism. PMID:24909063

  7. Characterizing Mucous Cell Remodeling in Cystic Fibrosis: Relationship to Neutrophils

    OpenAIRE

    Hays, Steven R.; John V Fahy

    2006-01-01

    Rationale: Relatively few studies have characterized mucous cells or mucins in detail in cystic fibrosis (CF), and the relationship between mucous cell abnormalities and neutrophilic inflammation is uncertain.

  8. Modulation of Neutrophil Chemokine Receptors by Staphylococcus aureus Supernate

    OpenAIRE

    Veldkamp, K. E.; Heezius, H. C. J. M.; Verhoef, J; Strijp, J.A.G. van; van Kessel, K. P. M.

    2000-01-01

    In a previous study, we showed that Staphylococcus aureus supernate (SaS) is a potent agonist for both neutrophils and mononuclear cells. To further investigate the immunomodulating effects of SaS, the effect on different neutrophil receptors was studied. Expression of various neutrophil receptors, before and after treatment with SaS, was quantified by flow cytometry. We found that SaS treatment of neutrophils resulted in a specific and total downregulation of the C5a and the fMLP receptor, b...

  9. Microwave circulator design

    CERN Document Server

    Linkhart, Douglas K

    2014-01-01

    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  10. Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

  11. Glutamine-Loaded Liposomes: Preliminary Investigation, Characterization, and Evaluation of Neutrophil Viability.

    Science.gov (United States)

    Costa, Larissa Chaves; Souza, Bárbara Nayane Rosário Fernandes; Almeida, Fábio Fidélis; Lagranha, Cláudia Jacques; Cadena, Pabyton Gonçalves; Santos-Magalhães, Nereide Stela; Lira-Nogueira, Mariane Cajubá de Britto

    2016-04-01

    Glutamine has received attention due to its ability to ameliorate the immune system response. Once conventional liposomes are readily recognized and captured by immune system cells, the encapsulation of glutamine into those nanosystems could be an alternative to reduce glutamine dosage and target then to neutrophils. Our goals were to nanoencapsulate glutamine into conventional liposomes (Gln-L), develop an analytical high-performance liquid chromatography (HPLC) method for its quantification, and evaluate the viability of neutrophils treated with Gln-L. Liposomes were prepared using the thin-film hydration technique followed by sonication and characterized according to pH, mean size, zeta potential, and drug encapsulation efficiency (EE%). We also aimed to study the effect of liposomal constituent concentrations on liposomal characteristics. The viability of neutrophils was assessed using flow cytometry after intraperitoneal administration of free glutamine (Gln), Gln-L, unloaded-liposome (UL), and saline solution as control (C) in healthy Wistar rats. The selected liposomal formulation had a mean vesicle size of 114.65 ± 1.82 nm with a polydispersity index of 0.30 ± 0.00, a positive surface charge of 36.30 ± 1.38 mV, and an EE% of 39.49 ± 0.74%. The developed chromatographic method was efficient for the quantification of encapsulated glutamine, with a retention time at 3.8 min. A greater viability was observed in the group treated with glutamine encapsulated compared to the control group (17%), although neutrophils remain viable in all groups. Thus, glutamine encapsulated into liposomes was able to increase the number of viable neutrophils at low doses, thereby representing a promising strategy for the treatment of immunodeficiency conditions. PMID:26228746

  12. Phagocytic responses of peritoneal macrophages and neutrophils are different in rats following prolonged exercise

    OpenAIRE

    Ferreira, Clílton K O; Jonato Prestes; DONATTO, FELIPE F.; Rozangela Verlengia; NAVALTA, JAMES W.; Cláudia R. Cavaglieri

    2010-01-01

    OBJECTIVE: To analyze the effects of exhausting long-duration physical exercise (swimming) sessions of different durations and intensities on the number and phagocytic capacity of macrophages and neutrophils in sedentary rats. INTRODUCTION: Exercise intensity, duration and frequency are important factors in determining immune response to physical effort. Thus, the effects of exhausting long-duration exercise are unclear. METHODS: Wistar rats were divided into two groups: an untreated group (m...

  13. Neutrophil Functions and Cytokines Expression Profile in Buffaloes with Impending Postpartum Reproductive Disorders

    OpenAIRE

    Patra, Manas Kumar; Harendra KUMAR; Nandi, Sukdeb

    2013-01-01

    The study was conducted to correlate the periparturient immune status in terms of neutrophil functions and cytokine expression in peripheral blood mononuclear cell culture with impending postpartum reproductive disorders in buffaloes. Forty pregnant buffaloes were observed for occurrence of postpartum reproductive disorders (PRD), i.e., metritis, endometritis and delayed uterine involution etc., during one week prepartum to four weeks postpartum period. A representative number (n = 6) of buff...

  14. Ranitidine improves postoperative monocyte and neutrophil function

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Nielsen, H; Jensen, S; Moesgaard, F

    1994-01-01

    BACKGROUND: The histamine H2-receptor antagonist ranitidine hydrochloride has been shown to improve trauma-, blood transfusion-, and sepsis-induced immunosuppression. OBJECTIVE: To evaluate the effect of ranitidine on postoperative impairment in monocyte and neutrophil function. METHODS: Twenty......-four patients undergoing major elective abdominal surgery were randomized to receive adjuvant treatment with ranitidine hydrochloride (100 mg) administered twice a day intravenously from skin incision for 4 days, followed by oral ranitidine hydrochloride (150 mg) administered twice a day for 5 days (n = 11), or...

  15. High levels of fish oil enhance neutrophil development and activation and influence colon mucus barrier function in a genetically susceptible mouse model.

    Science.gov (United States)

    Duriancik, David M; Comstock, Sarah S; Langohr, Ingeborg M; Fenton, Jenifer I

    2015-11-01

    Dietary fatty acids influence immunologic homeostasis, but their effect on initiation of colitis, an immune-mediated disease, is not well established. Previously, our laboratory demonstrated that high doses of dietary fish oil (FO) increased colon inflammation and dysplasia in a model of infection-induced colitis. In the current study, we assessed the effects of high-dose dietary FO, 6% by weight, on colon inflammation, neutrophil recruitment and function, and mucus layer integrity in a genetically susceptible, colitis-prone mouse model in the absence of infection. FO-fed SMAD3(-/-) mice had increased colon inflammation evidenced by increased numbers of systemic and local neutrophils and increased neutrophil chemoattractant and inflammatory cytokine gene expression in the colon. Mucus layer thickness in the cecum and goblet cell numbers in the cecum and colon in FO-fed mice were reduced compared to control. FO consumption affected colitis in male and female mice differently. Compared to female control mice, neutrophils from FO-fed female mice had reduced reactive oxygen species (ROS) upon ex vivo stimulation with phorbol myristate acetate while FO-fed male mice produced increased ROS compared to control-fed male mice. In summary, dietary FO impaired mucus layer integrity and was associated with colon inflammation characterized by increased neutrophil numbers and altered neutrophil function. High-dose FO may have detrimental effects in populations genetically susceptible for inflammatory bowel disease and these effects may differ between males and females. PMID:26297475

  16. Phagocytic responses of peritoneal macrophages and neutrophils are different in rats following prolonged exercise

    Directory of Open Access Journals (Sweden)

    Clílton K. O. Ferreira

    2010-01-01

    Full Text Available OBJECTIVE: To analyze the effects of exhausting long-duration physical exercise (swimming sessions of different durations and intensities on the number and phagocytic capacity of macrophages and neutrophils in sedentary rats. INTRODUCTION: Exercise intensity, duration and frequency are important factors in determining immune response to physical effort. Thus, the effects of exhausting long-duration exercise are unclear. METHODS: Wistar rats were divided into two groups: an untreated group (macrophage study and oyster glycogen-treated rats (neutrophil study. In each group, the animals were subdivided into five groups (10 rats per group: unexercised controls, an unadapted low-intensity exercise group, an unadapted moderate-intensity exercise group, a preadapted low-intensity exercise group and a preadapted moderate-intensity exercise group. All exercises were performed to exhaustion, and preadaptation consisted of 5, 15, 30 and 45 min sessions. RESULTS: Macrophage study: the number of peritoneal macrophages significantly decreased (9.22 ± 1.78 x 10(6 after unadapted exercise but increased (21.50 ± 0.63 x 10(6 after preadapted low-intensity exercise, with no changes in the moderate-intensity exercise group. Phagocytic capacity, however, increased by more than 80% in all exercise groups (low/moderate, unadapted/preadapted. Neutrophil study: the number of peritoneal neutrophils significantly decreased after unadapted (29.20 ± 3.34 x 10(6 and preadapted (50.00 ± 3.53 x 10(6 low-intensity exercise but increased after unadapted (127.60 ± 5.14 x 10(6 and preadapted (221.80 ± 14.85 x 10(6 moderate exercise. Neutrophil phagocytic capacity decreased by 63% after unadapted moderate exercise but increased by 90% after corresponding preadapted sessions, with no changes in the low-intensity exercise groups. CONCLUSION: Neutrophils and macrophages of sedentary rats respond differently to exercise-induced stress. Adaptation sessions reduce exercise

  17. Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

    Science.gov (United States)

    Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J H; Newman, Debra K; Newman, Peter J; Santoso, Sentot

    2010-04-01

    The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner. PMID:20194726

  18. Natural Circulation with Boiling

    International Nuclear Information System (INIS)

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed

  19. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors.

    Science.gov (United States)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels H H; Borregaard, Niels

    2013-10-01

    Neutrophils are indispensable in the innate immune defense against invading microorganisms. Neutrophils contain SVs and several subsets of granules that are essential for their function. Proteins present in neutrophil SVs and granules are synthesized during terminal granulopoiesis in the bone marrow. The heterogeneity of granules, as determined by marker proteins characteristic of each granule subset, is thought to result from differences in the biosynthetic windows of major classes of granule proteins, a process referred to as targeting by timing. Qualitative proteomic analysis of neutrophil granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in-gel-digested with trypsin. The resulting peptides were analyzed using LTQ Orbitrap XL tandem MS. A total of 1292 unique proteins were identified and grouped, according to the neutrophil fraction, in which they displayed maximal expression. In addition to various known neutrophil proteins, several uncharacterized proteins were found, as well as proteins not described previously in neutrophils. To study the correlation between mRNA expression in neutrophil precursors and the localization of their cognate proteins, the distribution of 126 identified proteins was compared with their mRNA expression profiles. The neutrophil subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes. PMID:23650620

  20. Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils

    OpenAIRE

    Kobayashi, Scott D.; Braughton, Kevin R.; Whitney, Adeline R.; Voyich, Jovanka M.; Schwan, Tom G.; Musser, James M.; DeLeo, Frank R.

    2003-01-01

    Human polymorphonuclear leukocytes (PMNs or neutrophils) are essential to the innate immune response against bacterial pathogens. Recent evidence suggests that PMN apoptosis facilitates resolution of inflammation during bacterial infection. Although progress has been made toward understanding apoptosis in neutrophils, very little is known about transcriptional regulation of this process during bacterial infection. To gain insight into the molecular processes that facilitate resolution of infe...

  1. Influence of recombinant bovine gamma interferon on neutrophil function

    International Nuclear Information System (INIS)

    To determine the role of cytokines in enhancing neutrophil function, peripheral blood neutrophils from healthy cattle were preincubated with recombinant bovine gamma interferon (rboIFN-gamma). Pretreatment of neutrophils with rboIFN-gamma activated neutrophils to have enhanced antibody-dependent (ADCC) and -independent (AINC) cytotoxicity and impaired random migration. Neutrophil ingestion, superoxide anion production, and iodination activity were not consistently affected by rboIFN-gamma pretreatment. In order to better understand the activation process, the molecular events involved in the enhancement of neutrophil cytotoxicity and the inhibition random migration were investigated. Both RNA and protein syntheses by neutrophils were required for the enhancement of AINC activity and the inhibition of random migration, but were not required for the enhancement of ADCC by rboIFN-gamma. Specifically, rbo-IFN-gamma treatment of neutrophils enhanced the expression of two major proteins of molecular mass 60,000 and 94,000 as determined by SDS-polyacrylamide, linear-gradient gel electrophoresis and 35S-fluorography

  2. Promoting metastasis: neutrophils and T cells join forces.

    Science.gov (United States)

    Fridlender, Zvi G; Albelda, Steven M; Granot, Zvi

    2015-07-01

    The role neutrophils play in cancer is a matter of debate as both pro- and anti-tumor functions have been documented. In a recent publication in Nature, Coffelt et al. identify a new mechanism where neutrophils and T cells cooperate to generate metastasis-supporting immune suppression. PMID:26138787

  3. Localization and Functionality of the Inflammasome in Neutrophils

    DEFF Research Database (Denmark)

    Bakele, Martina; Joos, Melanie; Burdi, Sofia;

    2014-01-01

    distinct intracellular compartments and release IL-1β and IL-18, but not IL-1α or IL-33 protein. Targeting the neutrophil inflammasome may represent a future therapeutic strategy to modulate neutrophilic inflammatory diseases, such as cystic fibrosis, rheumatoid arthritis, or sepsis....

  4. NEUTROPHIL MIGRATION UNDER AGAROSE IS ALTERED BY COPPER DEFICIENCY

    Science.gov (United States)

    Dietary copper deficiency alters neutrophil sequestration and margination within the pulmonary microcirculation in rats. In the current study, the role of copper in CD1 lb/CD18-dependent an -independent migration of neutrophils under agarose was studied. Male, weanling Sprague-Dawley rats were fed p...

  5. Human neutrophil elastase detection with fluorescent peptide sensors conjugated to cellulosic and nanocellulosic materials: part II, structure/function analysis

    Science.gov (United States)

    Human neutrophil elastase (HNE) is one of a number of proteases that is receiving increased attention as a marker for inflammatory diseases and sensor-based point of care diagnostics. Integral to sensor-based detection is the transducer surface which is the platform of the sensor's signal transmitta...

  6. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  7. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    Directory of Open Access Journals (Sweden)

    Ritankar Majumdar

    2016-01-01

    Full Text Available Leukotriene B4 (LTB4 is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments.

  8. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    Science.gov (United States)

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. PMID:26741884

  9. Neutrophils--a key component of ischemia-reperfusion injury.

    Science.gov (United States)

    Schofield, Zoe Victoria; Woodruff, Trent Martin; Halai, Reena; Wu, Mike Chia-Lun; Cooper, Matthew Allister

    2013-12-01

    Ischemia-reperfusion injury (IRI) is a common occurrence following myocardial infarction, transplantation, stroke, and trauma that can lead to multiple organ failure, which remains the foremost cause of death in critically ill patients. Current therapeutic strategies for IRI are mainly palliative, and there is an urgent requirement for a therapeutic that could prevent or reverse tissue damage caused by IRI. Neutrophils are the primary responders following ischemia and reperfusion and represent important components in the protracted inflammatory response and severity associated with IRI. Experimental studies demonstrate neutrophil infiltration at the site of ischemia and show that inducing neutropenia can protect organs from IRI. In this review, we highlight the mechanisms involved in neutrophil recruitment, activation, and adherence and how this contributes to disease severity in IRI. Inhibiting neutrophil mobilization, tissue recruitment, and ultimately neutrophil-associated activation of local and systemic inflammatory responses may have therapeutic potential in the amelioration of local and remote tissue damage following IRI. PMID:24088997

  10. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

    Science.gov (United States)

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A.

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. PMID:26741884

  11. The neutrophil-specific antigen CD177 is a counter-receptor for platelet endothelial cell adhesion molecule-1 (CD31).

    Science.gov (United States)

    Sachs, Ulrich J H; Andrei-Selmer, Cornelia L; Maniar, Amudhan; Weiss, Timo; Paddock, Cathy; Orlova, Valeria V; Choi, Eun Young; Newman, Peter J; Preissner, Klaus T; Chavakis, Triantafyllos; Santoso, Sentot

    2007-08-10

    Human neutrophil-specific CD177 (NB1 and PRV-1) has been reported to be up-regulated in a number of inflammatory settings, including bacterial infection and granulocyte-colony-stimulating factor application. Little is known about its function. By flow cytometry and immunoprecipitation studies, we identified platelet endothelial cell adhesion molecule-1 (PECAM-1) as a binding partner of CD177. Real-time protein-protein analysis using surface plasmon resonance confirmed a cation-dependent, specific interaction between CD177 and the heterophilic domains of PECAM-1. Monoclonal antibodies against CD177 and against PECAM-1 domain 6 inhibited adhesion of U937 cells stably expressing CD177 to immobilized PECAM-1. Transendothelial migration of human neutrophils was also inhibited by these antibodies. Our findings provide direct evidence that neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1. This interaction may constitute a new pathway that participates in neutrophil transmigration. PMID:17580308

  12. Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

    OpenAIRE

    Schilder, Louise; Nurmohamed, Shaikh Azam; Wee, Piet; Paauw, Nanne; Girbes, Armand; Beishuizen, Albertus; Beelen, Robert; Groeneveld, Johan

    2014-01-01

    textabstractBackground: During continuous venovenous haemofiltration (CVVH), regional anticoagulation with citrate may be superior to heparin in terms of biocompatibility, since heparin as opposed to citrate may activate complement (reflected by circulating C5a) and induce neutrophil degranulation in the filter and myeloperoxidase (MPO) release from endothelium. Methods. No anticoagulation (n = 13), unfractionated heparin (n = 8) and trisodium citrate (n = 17) regimens during CVVH were compar...

  13. Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

    OpenAIRE

    Schilder, Louise; Nurmohamed, S Azam; ter Wee, Pieter M.; Paauw, Nanne J.; Girbes, Armand RJ; Beishuizen, Albertus; Beelen, Robert HJ; Groeneveld, AB Johan

    2014-01-01

    Background During continuous venovenous haemofiltration (CVVH), regional anticoagulation with citrate may be superior to heparin in terms of biocompatibility, since heparin as opposed to citrate may activate complement (reflected by circulating C5a) and induce neutrophil degranulation in the filter and myeloperoxidase (MPO) release from endothelium. Methods No anticoagulation (n = 13), unfractionated heparin (n = 8) and trisodium citrate (n = 17) regimens during CVVH were compared. Blood samp...

  14. CXC Receptor 1 and 2 and Neutrophil Elastase Inhibitors Alter Radiation-induced Lung Disease in the Mouse

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jessica [Department of Medicine and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec (Canada); Haston, Christina K., E-mail: christina.haston@mcgill.ca [Department of Medicine and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec (Canada)

    2013-01-01

    Purpose: We previously reported increased numbers of neutrophils to be associated with the development of the radiation-induced lung responses of alveolitis (pneumonitis) and fibrosis in mice. In the present study we investigated whether CXC receptor 1 and 2 antagonism with DF2156A, a small molecule inhibitor of neutrophil chemotaxis, or the neutrophil elastase inhibitor sivelestat decreases the lung response to irradiation. Methods and Materials: KK/HIJ mice received 14 Gy whole-thorax irradiation, and a subset of them received drug treatment 3 times per week from the day of irradiation until they were killed because of respiratory distress symptoms. Results: Irradiated mice receiving sivelestat survived 18% longer than did mice receiving radiation alone (73 vs 60 days for female mice, 91 vs 79 days for male mice), whereas postirradiation survival times did not differ between the group of mice receiving DF2156A and the radiation-only group. The numbers of neutrophils in lung tissue and in bronchoalveolar lavage fluid did not differ among groups of irradiated mice, but they significantly exceeded the levels in unirradiated control mice. The extent of alveolitis, assessed histologically, did not differ between irradiated mice treated with either drug and those receiving radiation alone, when assessed at the end of the experiment, but it was significantly reduced, as were the neutrophil measures, in sivelestat-treated mice at the common kill time of 60 days after irradiation. Mice treated with radiation and DF2156A developed significantly less fibrosis than did mice receiving radiation alone, and this difference was associated with decreased expression of interleukin-13 in lung tissue. Conclusions: We conclude that neutrophil elastase inhibition affects alveolitis and prolongs survival, whereas CXCR1/2 antagonism reduces radiation-induced fibrotic lung disease in mice without affecting the onset of distress.

  15. CXC Receptor 1 and 2 and Neutrophil Elastase Inhibitors Alter Radiation-induced Lung Disease in the Mouse

    International Nuclear Information System (INIS)

    Purpose: We previously reported increased numbers of neutrophils to be associated with the development of the radiation-induced lung responses of alveolitis (pneumonitis) and fibrosis in mice. In the present study we investigated whether CXC receptor 1 and 2 antagonism with DF2156A, a small molecule inhibitor of neutrophil chemotaxis, or the neutrophil elastase inhibitor sivelestat decreases the lung response to irradiation. Methods and Materials: KK/HIJ mice received 14 Gy whole-thorax irradiation, and a subset of them received drug treatment 3 times per week from the day of irradiation until they were killed because of respiratory distress symptoms. Results: Irradiated mice receiving sivelestat survived 18% longer than did mice receiving radiation alone (73 vs 60 days for female mice, 91 vs 79 days for male mice), whereas postirradiation survival times did not differ between the group of mice receiving DF2156A and the radiation-only group. The numbers of neutrophils in lung tissue and in bronchoalveolar lavage fluid did not differ among groups of irradiated mice, but they significantly exceeded the levels in unirradiated control mice. The extent of alveolitis, assessed histologically, did not differ between irradiated mice treated with either drug and those receiving radiation alone, when assessed at the end of the experiment, but it was significantly reduced, as were the neutrophil measures, in sivelestat-treated mice at the common kill time of 60 days after irradiation. Mice treated with radiation and DF2156A developed significantly less fibrosis than did mice receiving radiation alone, and this difference was associated with decreased expression of interleukin-13 in lung tissue. Conclusions: We conclude that neutrophil elastase inhibition affects alveolitis and prolongs survival, whereas CXCR1/2 antagonism reduces radiation-induced fibrotic lung disease in mice without affecting the onset of distress.

  16. Circulating Extracellular microRNA in Systemic Autoimmunity

    DEFF Research Database (Denmark)

    Heegaard, Niels H. H.; Carlsen, Anting Liu; Skovgaard, Kerstin;

    2015-01-01

    , extracellular miRNA is protected against degradation by complexation with carrier proteins and/or by being enclosed in subcellular membrane vesicles. This, together with their tissue- and disease-specific expression, has fuelled the interest in using circulating microRNA profiles as harbingers of disease, i......, natural killer cells, neutrophil granulocytes, and monocyte-macrophages. Exploratory studies (only validated in a few cases) also show that specific profiles of circulating miRNAs are associated with different systemic autoimmune diseases including systemic lupus erythematosus (SLE), systemic sclerosis...... systemic autoimmunity and summarize some proposed functions of miRNAs in immune regulation and dysregulation. We conclude that the studies suggest new hypotheses and additional experiments, and that further diagnostic development is highly dependent on analytical method development and on obtaining...

  17. Circulating lethal toxin decreases the ability of neutrophils to respond to Bacillus anthracis.

    Science.gov (United States)

    Weiner, Zachary P; Ernst, Stephen M; Boyer, Anne E; Gallegos-Candela, Maribel; Barr, John R; Glomski, Ian J

    2014-04-01

    Polymorphonuclear leucocytes (PMNs) play a protective role during Bacillus anthracis infection. However, B. anthracis is able to subvert the PMN response effectively as evidenced by the high mortality rates of anthrax. One major virulence factor produced by B. anthracis, lethal toxin (LT), is necessary for dissemination in the BSL2 model of mouse infection. While human and mouse PMNs kill vegetative B. anthracis, short in vitro half-lives of PMNs have made it difficult to determine how or if LT alters their bactericidal function. Additionally, the role of LT intoxication on PMN's ability to migrate to inflammatory signals remains controversial. LF concentrations in both serum and major organs were determined from mice infected with B. anthracis Sterne strain at defined stages of infection to guide subsequent administration of purified toxin. Bactericidal activity of PMNs assessed using ex vivo cell culture assays showed significant defects in killing B. anthracis. In vivo PMN recruitment to inflammatory stimuli was significantly impaired at 24 h as assessed by real-time analysis of light-producing PMNs within the mouse. The observations described above suggest that LT serves dual functions; it both attenuates accumulation of PMNs at sites of inflammation and impairs PMNs bactericidal activity against vegetative B. anthracis. PMID:24152301

  18. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.

    Science.gov (United States)

    Drewniak, Agata; Gazendam, Roel P; Tool, Anton T J; van Houdt, Michel; Jansen, Machiel H; van Hamme, John L; van Leeuwen, Ester M M; Roos, Dirk; Scalais, Emmanuel; de Beaufort, Carine; Janssen, Hans; van den Berg, Timo K; Kuijpers, Taco W

    2013-03-28

    Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule in the cytosol of myeloid cells, required for induction of T-helper cells producing interleukin-17 (Th17 cells) and important in antifungal immunity. In a patient suffering from Candida dubliniensis meningoencephalitis, mutations in the CARD9 gene were found to result in the loss of protein expression. Apart from the reduced numbers of CD4(+) Th17 lymphocytes, we identified a lack of monocyte-derived cytokines in response to Candida strains. Importantly, CARD9-deficient neutrophils showed a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae. The neutrophil killing defect was independent of the generation of reactive oxygen species by the reduced NAD phosphate oxidase system. Taken together, this demonstrates that human CARD9 deficiency results in selective defect in the host defense against invasive fungal infection, caused by an impaired phagocyte killing. PMID:23335372

  19. Concepts in Assisted Circulation

    OpenAIRE

    Lefemine, Armand A.; Dunbar, Jacob; DeLucia, Anthony

    1986-01-01

    Assisted circulation by extracorporeal and extracardiac bypass techniques must be based on the requirements of the heart and of the total body, though these may differ. The cardiac problem in cardiogenic shock is more likely to be a biventricular problem demanding decompression of both sides. Extra pulmonary oxygenation should be avoided because of complexity in long-term use. Principles of assisted circulation may be applied in an extra-thoracic temporary manner or as an intracorporeal long-...

  20. A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: The focus of this study was to characterize a novel biomarker for cystic fibrosis (CF) that could reflect exacerbations of the disease and could be useful for therapeutic stratification of patients, or for testing of potential drug treatments. This study focused exclusively on a protein complex containing alpha-1 antitrypsin and CD16b (AAT:CD16b) which is released into the bloodstream from membranes of pro-inflammatory primed neutrophils. METHODS: Neutrophil membrane expression and extracellular levels of AAT and CD16b were quantified by flow cytometry, Western blot analysis and by 2D-PAGE. Interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and AAT:CD16b complex were quantified in CF plasma (n=38), samples post antibiotic treatment for 14days (n=10), chronic obstructive pulmonary disease (n=10), AAT deficient (n=10) and healthy control (n=14) plasma samples by ELISA. RESULTS: Cell priming with IL-8 and TNF-alpha caused release of the AAT:CD16b complex from the neutrophil cell membrane. Circulating plasma levels of IL-8, TNF-alpha and AAT:CD16b complex were significantly higher in patients with CF than in the other patient groups or healthy controls (P<0.05). Antibiotic treatment of pulmonary exacerbation in patients with CF led to decreased plasma protein concentrations of AAT:CD16b complex with a significant correlation with improved FEV1 (r=0.81, P=0.003). CONCLUSION: The results of this study have shown that levels of AAT:CD16b complex present in plasma correlate to the inflammatory status of patients. The AAT:CD16b biomarker may become a useful addition to the clinical diagnosis of exacerbations in CF.

  1. Age associated variations in human neutrophil and sperm functioning

    Institute of Scientific and Technical Information of China (English)

    Kaveri Purandhar; Sriram Seshadri

    2013-01-01

    Objective: To determine the functional and biochemical variations in sperm and the neutrophil with the progression of age. Methods: Ninety healthy male subjects were selected in the age group 26-40 for the collection of semen and blood samples were collected. Basic semen analysis, hematogram, differential count serum analysis, seminal plasma and serum biochemistry was performed. Mitochondrial isolation from sperm and neutrophil was done to ascertain mitochondrial markers. Results: Our data shows a significant age-dependent reduction in the levels of mitochondrial Superoxide Dismutase (SOD) and Catalase (CAT) in sperm and the neutrophil. The functional attributes of sperm and neutrophil did not show any specific trend.Conclusion:The decreasing trend of the mitochondrial antioxidants enzymes in the sperm and the neutrophil is an indicative of the reduction in the functioning of sperm and the neutrophil. The antioxidants enzymes of sperm and neutrophil shows similar declining trend with the progression of age suggesting its possible role as a prognostic marker for age related deformities and even in male fertility.

  2. Characterization of neutrophil adhesion to different titanium surfaces

    Indian Academy of Sciences (India)

    V Campos; R C N Melo; L P Silva; E N Aquino; M S Castro; W Fontes

    2014-02-01

    Although titanium (Ti) is known to elicit a foreign body response when implanted into humans, Ti implant healing resembles normal wound healing in terms of inflammatory cell recruitment and inflammation persistence. Rough implant surfaces may present better conditions for protein adsorption and for the adhesion of platelets and inflammatory cells such as neutrophils. Implanted biomedical devices initially interact with coagulating blood; however, direct contact between the oxide layer of the implant and neutrophils has not been completely described. The aim of the present study is to compare the behaviours of neutrophils in direct contact with different Ti surfaces. Isolated human neutrophils were placed into contact with Ti discs, which had been rendered as `smooth' or `rough', following different surface treatments. Scanning electron microscopy and flow cytometry were used to measure cell adhesion to the surfaces and exposure of membrane proteins such as CD62L and CD11b. Topographic roughness was demonstrated as higher for SLA treated surfaces, measured by atomic force microscopy and elemental analysis was performed by energy dispersive X-ray, showing a similar composition for both surfaces. The adhesion of neutrophils to the `rough' Ti surface was initially stronger than adhesion to the `smooth' surface. The cell morphology and adhesion marker results revealed clear signs of neutrophil activation by either surface, with different neutrophil morphological characteristics being observed between the two surface types. Understanding the cellular mechanisms regulating cell–implant interactions should help researchers to improve the surface topography of biomedical implant devices.

  3. Optimization of reverse circulation bit based on field experiment

    Institute of Scientific and Technical Information of China (English)

    Hong REN; Kun YIN; Kun BO

    2008-01-01

    By field experiment in Sandaozhuang W-Mo mining area in Luanchuan of Henan Province, the authors analyzed the Experimental result of reverse circulation bit on the basis of different structures and obtained the following conclusion: the design parameter of reverse circulation bit, the number, diameter and angle of the spurt hole can influence on the reverse circulation effect. The bit with inner spurt hole is better obviously than that one without inner spurt hole in reverse circulation, one or two right and the best choice of inner spurt hole is that the diameter is Φ8, the angle is 30° dip up and the suitable number is two to three.

  4. Neutrophil extracellular traps in sheep mastitis.

    Science.gov (United States)

    Pisanu, Salvatore; Cubeddu, Tiziana; Pagnozzi, Daniela; Rocca, Stefano; Cacciotto, Carla; Alberti, Alberto; Marogna, Gavino; Uzzau, Sergio; Addis, Maria Filippa

    2015-01-01

    Neutrophil extracellular traps (NETs) are structures composed of DNA, histones, and antimicrobial proteins that are released extracellularly by neutrophils and other immune cells as a means for trapping and killing invading pathogens. Here, we describe NET formation in milk and in mammary alveoli of mastitic sheep, and provide a dataset of proteins found in association to these structures. Nucleic acid staining, immunomicroscopy and fluorescent in-situ hybridization of mastitic mammary tissue from sheep infected with Streptococcus uberis demonstrated the presence of extranuclear DNA colocalizing with antimicrobial proteins, histones, and bacteria. Then, proteomic analysis by LTQ-Orbitrap Velos mass spectrometry provided detailed information on protein abundance changes occurring in milk upon infection. As a result, 1095 unique proteins were identified, of which 287 being significantly more abundant in mastitic milk. Upon protein ontology classification, the most represented localization classes for upregulated proteins were the cytoplasmic granule, the nucleus, and the mitochondrion, while function classes were mostly related to immune defence and inflammation pathways. All known NET markers were massively increased, including histones, granule proteases, and antimicrobial proteins. Of note was the detection of protein arginine deiminases (PAD3 and PAD4). These enzymes are responsible for citrullination, the post-translational modification that is known to trigger NET formation by inducing chromatin decondensation and extracellular release of NETs. As a further observation, citrullinated residues were detected by tandem mass spectrometry in histones of samples from mastitic animals. In conclusion, this work provides novel microscopic and proteomic information on NETs formed in vivo in the mammary gland, and reports the most complete database of proteins increased in milk upon bacterial mastitis. PMID:26088507

  5. Neutrophil Transmigration Mediated by the Neutrophil-Specific Antigen CD177 Is Influenced by the Endothelial S536N Dimorphism of Platelet Endothelial Cell Adhesion Molecule-1

    OpenAIRE

    Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J. H.; Newman, Debra K.; Newman, Peter J.; Santoso, Sentot

    2010-01-01

    The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S536N single nucleotide polymorphism of two major isoforms V98N536G643 and L98S536R643 and a yet-t...

  6. Neutrophil adhesion and chemotaxis depend on substrate mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Jannat, Risat A; Hammer, Daniel A [Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 (United States); Robbins, Gregory P; Ricart, Brendon G [Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 311A Towne Building, 220 South 33rd Street, Philadelphia, PA 19104 (United States); Dembo, Micah, E-mail: hammer@seas.upenn.ed [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States)

    2010-05-19

    Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K{sub D} of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against {beta}{sub 2}-integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

  7. Neutrophil localization in acute and chronic experimental abscesses

    International Nuclear Information System (INIS)

    Abdominal abscesses are associated with a high mortality, and usually require surgical drainage for cure. A potential mechanism explaining the inability of the host to clear this infection may be in part a result of the inability of the neutrophil to localize at the site of an established infection. To study this question, either acute (4 hours old) or chronic (2 weeks old) abscesses caused by Staphylococcus aureus were created in perforated capsules implanted in the peritoneal cavity of rabbits. Homologous neutrophils were obtained from donor rabbits 4 hours after peritoneal glycogen stimulation and labeled with indium 111 oxine. Only 0.71% of injected 111In-labeled neutrophils localized in the chronic abscesses, compared with 1.77% in acute abscesses (P less than or equal to 0.01). Animals with chronic infections had a lower intravascular recovery of injected neutrophils (P less than 0.002). Failure of neutrophil localization was not associated with less chemotactic activity within the abscess, as measured by a chemotaxis-under-agarose assay, or caused by a barrier surrounding the abscess as detected by radionuclide imaging. Only 0.07% of injected neutrophils localized into acute abdominal abscesses in animals with a concomitant chronic subcutaneous abscess. These chronically infected animals also demonstrated a low peak intravascular recovery of injected neutrophils when compared with animals with only an acute infection (P less than 0.002). These data reveal that neutrophils localize to abscesses poorly in animals with chronic infections. The mechanism is possibly related to a systemic factor(s) associated with a lower intravascular recovery of injected neutrophils in chronically infected animals

  8. Changes in some Blood Micronutrients, Leukocytes and Neutrophil Expression of Adhesion Molecules in Periparturient Dairy Cows

    Directory of Open Access Journals (Sweden)

    Petersson L

    2001-03-01

    Full Text Available Dairy cows are highly susceptible to infectious diseases, like mastitis, during the period around calving. Although factors contributing to increased susceptibility to infection have not been fully elucidated, impaired neutrophil recruitment to the site of infection and changes in the concentrations of some micronutrients related with the function of the immune defence has been implicated. Most of the current information is based on studies outside the Nordic countries where the conditions for dairy cows are different. Therefore, the aim of the study was to evaluate changes in blood concentrations of the vitamins A and E, the minerals calcium (Ca, phosphorous (P, and magnesium (Mg, the electrolytes potassium (K and sodium (Na and the trace elements selenium (Se, copper (Cu and zinc (Zn, as well as changes in total and differential white blood cell counts (WBC and expression of the adhesion molecules CD62L and CD18 on blood neutrophils in Swedish dairy cows during the period around calving. Blood samples were taken from 10 cows one month before expected calving, at calving and one month after calving. The results were mainly in line with reports from other countries. The concentrations of vitamins A and E, and of Zn, Ca and P decreased significantly at calving, while Se, Cu, and Na increased. Leukocytosis was detected at calving, mainly explained by neutrophilia, but also by monocytosis. The numbers of lymphocytes tended to decrease at the same time. The mean fluorescent intensity (MFI of CD62L and CD18 molecules on blood neutrophils remained constant over time. The proportion of CD62L+ neutrophils decreased significantly at calving. The animals were fed according to, or above, their requirements. Therefore, changes in blood levels of vitamins, minerals and trace elements were mainly in response to colostrum formation, changes in dry matter intake, and ruminal metabolism around calving. Decreased levels of vitamins A and E, and of Zn at calving

  9. Spinal cord injury in rats: inability of nimodipine or anti-neutrophil serum to improve spinal cord blood flow or neurologic status

    International Nuclear Information System (INIS)

    The role of a calcium-mediated increase in vascular resistance and of vascular damage caused by polymorphonuclear leukocytes (PMNLs) in the development of neurologic deficit and disturbance of spinal cord circulation following spinal cord compression was studied in the rat. Spinal cord injury was induced by 5 min of compression with a load of 35 g on a 2.2 x 5.0 mm compression plate. This caused transient paraparesis. The rats received either the calcium receptor antagonist nimodipine or an anti-rat neutrophil serum (ANS). Nimodipine was infused i.v. for 4 h in an amount of 1.5 μg/kg/min starting 60 min after trauma. The number of circulating PMNLs was depleted by intraperiotoneal injection of an ANS raised in sheep given 12 h before trauma. This caused a reduction to about 2% of the pre-ANS value. Controls received saline or normal sheep serum. The motor performance was assessed daily on the inclined plane. On day one, the day after injury, the capacity angle had decreased from about 63 deg. preoperatively to close to 32 deg. in the experimental groups. There was then a slow improvement in both the control and experimental groups and on day 4 the capacity angle was close to 43 deg. in all 3 groups. Spinal cord blood flow, as measured with the 14C-iodoantipyrine autoradiography method, was similar in all groups on day 4. As neither the neurologic dysfunction nor the spinal cord blood flow was affected by post-trauma treatment with nimodipine or pretreatment with ANS, the possibility that calcium-mediated vasoconstriction or PMNLs play a role in the development of posttraumatic neuroligic disability was not supported by this study. (author)

  10. Real-time imaging of endothelial cell-cell junctions during neutrophil transmigration under physiological flow.

    Science.gov (United States)

    Kroon, Jeffrey; Daniel, Anna E; Hoogenboezem, Mark; van Buul, Jaap D

    2014-01-01

    During inflammation, leukocytes leave the circulation and cross the endothelium to fight invading pathogens in underlying tissues. This process is known as leukocyte transendothelial migration. Two routes for leukocytes to cross the endothelial monolayer have been described: the paracellular route, i.e., through the cell-cell junctions and the transcellular route, i.e., through the endothelial cell body. However, it has been technically difficult to discriminate between the para- and transcellular route. We developed a simple in vitro assay to study the distribution of endogenous VE-cadherin and PECAM-1 during neutrophil transendothelial migration under physiological flow conditions. Prior to neutrophil perfusion, endothelial cells were briefly treated with fluorescently-labeled antibodies against VE-cadherin and PECAM-1. These antibodies did not interfere with the function of both proteins, as was determined by electrical cell-substrate impedance sensing and FRAP measurements. Using this assay, we were able to follow the distribution of endogenous VE-cadherin and PECAM-1 during transendothelial migration under flow conditions and discriminate between the para- and transcellular migration routes of the leukocytes across the endothelium. PMID:25146919

  11. Effect of colchicine on viscoelastic properties of neutrophils.

    OpenAIRE

    Chien, S; Sung, K L

    1984-01-01

    The effect of colchicine (15-60 micrograms/ml) on the viscoelastic properties of human neutrophils was studied by the micropipette technique. The small deformation of the neutrophil in response to a step aspiration pressure was analyzed by using a three-element model in which an elastic element, K1, is in parallel with a Maxwell element composed of another elastic element, K2, in series with a viscous element, mu. Colchicine treatment of neutrophils caused decreases in K2 and mu without affec...

  12. Chemotactic peptide modulation of actin assembly and locomotion in neutrophils

    OpenAIRE

    1984-01-01

    To determine the relationship between the state of actin polymerization in neutrophils and the formyl-methionyl-leucyl-phenylalanine (fMLP)- induced changes in the locomotive behavior of neutrophils, the mean rate of locomotion (mROL), the percent G-actin, and the relative F- actin content of neutrophils were determined. The mROL was quantified by analysis of the locomotion of individual cells; the percentage of total actin as G-actin was measured by DNase I inhibition; and the F- actin was d...

  13. [Neutrophilic dermatosis in ulcerative colitis occurring in advanced age].

    Science.gov (United States)

    López Maldonado, M D; Calvo Catalá, J; Ronda Gasulla, A; Hortelano Martínez, E; Herrera Ballester, A; Febrer Bosch, I

    1994-08-01

    The Neutrophilic dermatosis (ND) is considered as an independent entity with diverse clinical manifestations among which there are: gangrenous pyoderma, nodous erythema, Sweets Syndrome, vesiculopustula eruptions associated to ulcerous colitis and intestinal short circuit syndrome with or without short circuit. Histologically, they are characterized by infiltration of polymorphonuclear neutrophils, generally at the dermic level, but also at the epidermic. They are usually associated to systemic diseases, especially to chronic intestinal inflammatory disease. Our aim was to describe two forms of clinical presentation of neutrophilic dermatosis: gangrenous pyoderma and vesiculopustula eruption, associated to ulcerous colitis starting at advances ages. PMID:7772690

  14. Vaccination of mice against H. pylori induces a strong Th-17 response and immunity that is neutrophil-dependent

    Science.gov (United States)

    DeLyria, Elizabeth S.; Redline, Raymond W.; Blanchard, Thomas G.

    2016-01-01

    Background & Aims Vaccine efficacy against gastric Helicobacter pylori infection has been demonstrated in mice, but little is known about the effector mechanisms of bacterial clearance. Our aim was to investigate a possible T cell-neutrophil pathway of vaccine-induced protection. Methods Nonimmune and immunized mice were compared for their response to H. pylori challenge. T cell responses were assessed by recall assays. IL-17-induced chemokine production by leukocyte and nonleukocyte cells was evaluated by cytokine ELISA. In a kinetic study, biopsies were collected at multiple time points post-challenge and assessed for bacterial load and inflammation. Relative levels of T cells, IL-17, IFNγ, MIP-2, KC, and LIX were determined by quantitative PCR. The role of neutrophils was evaluated by antibody-mediated depletion of neutrophils following challenge. Results Immunization induced strong IFNγ and IL-17-producing T cell responses, and IL-17 was capable of inducing significant amounts of KC and MIP-2 from dendritic cells, macrophages, fibroblasts, and gastric epithelial cells. Challenge of immunized mice induced significantly greater gastritis than infected mice, preceding significantly lower bacterial loads by day 7. In immune mice, T cell recruitment to the gastric mucosa correlated with a continuous rise in IL-17 and IFNγ, followed by KC, MIP-2, and LIX production and the recruitment of significant numbers of neutrophils by day 5. Antibody-mediated depletion of neutrophils abrogated vaccine efficacy. Conclusions Vaccination of mice against H. pylori results in a significant Th-17 cell recall response associated with increases in chemokines that attract neutrophils to the stomach which are important for eradication of H. pylori. PMID:18948106

  15. Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice

    International Nuclear Information System (INIS)

    Previously, we have reported that thalidomide can modulate the immune responses in female B6C3F1 mice. Furthermore, thalidomide immunomodulation increased primary host resistance to intravenously infected Listeria monocytogenes. The present study was intended to evaluate the mechanisms underlying the enhanced host resistance to L. monocytogenes by focusing on the neutrophils. Female B6C3F1 mice were treated intraperitoneally with thalidomide (100 mg/kg) for 15 days. Exposure to thalidomide increased the numbers of neutrophils in the spleens and livers of L. monocytogenes-infected mice when compared to the L. monocytogenes-infected control mice. Additionally, the percentage of neutrophils was also significantly increased after Thd treatment in L. monocytogenes-infected mice. Further studies using antibodies to deplete corresponding cells indicated that thalidomide-mediated increase in primary host resistance (both the moribundity and colony counts in the liver and spleen) to L. monocytogenes infection was due to its effect on neutrophils but not CD8+ T cells or NK cells. Finally, Thd exposure also increased host resistance to secondary host resistance to L. monocytogenes infection, and depletion of neutrophils abolished the protective effect. In conclusion, thalidomide enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice

  16. Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice.

    Science.gov (United States)

    Guo, Tai L; Chi, Rui P; Karrow, Niel A; Zhang, Ling X; Pruett, Stephen B; Germolec, Dori R; White, Kimber L

    2005-12-15

    Previously, we have reported that thalidomide can modulate the immune responses in female B6C3F1 mice. Furthermore, thalidomide immunomodulation increased primary host resistance to intravenously infected Listeria monocytogenes. The present study was intended to evaluate the mechanisms underlying the enhanced host resistance to L. monocytogenes by focusing on the neutrophils. Female B6C3F1 mice were treated intraperitoneally with thalidomide (100 mg/kg) for 15 days. Exposure to thalidomide increased the numbers of neutrophils in the spleens and livers of L. monocytogenes-infected mice when compared to the L. monocytogenes-infected control mice. Additionally, the percentage of neutrophils was also significantly increased after Thd treatment in L. monocytogenes-infected mice. Further studies using antibodies to deplete corresponding cells indicated that thalidomide-mediated increase in primary host resistance (both the moribundity and colony counts in the liver and spleen) to L. monocytogenes infection was due to its effect on neutrophils but not CD8+ T cells or NK cells. Finally, Thd exposure also increased host resistance to secondary host resistance to L. monocytogenes infection, and depletion of neutrophils abolished the protective effect. In conclusion, thalidomide enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice. PMID:15921716

  17. Gaussian Fibonacci Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices have become important tools in solving integrable system, Hamiltonian structure, and integral equations. In this paper, we prove that Gaussian Fibonacci circulant type matrices are invertible matrices for n>2 and give the explicit determinants and the inverse matrices. Furthermore, the upper bounds for the spread on Gaussian Fibonacci circulant and left circulant matrices are presented, respectively.

  18. Skyscraper Numbers

    OpenAIRE

    Khovanova, Tanya; Lewis, Joel Brewster

    2013-01-01

    We introduce numbers depending on three parameters which we call skyscraper numbers. We discuss properties of these numbers and their relationship with Stirling numbers of the first kind, and we also introduce a skyscraper sequence.

  19. Genetic mechanism of human neutrophil antigen 2 deficiency and expression variations.

    Science.gov (United States)

    Li, Yunfang; Mair, David C; Schuller, Randy M; Li, Ling; Wu, Jianming

    2015-05-01

    Human neutrophil antigen 2 (HNA-2) deficiency is a common phenotype as 3-5% humans do not express HNA-2. HNA-2 is coded by CD177 gene that associates with human myeloproliferative disorders. HNA-2 deficient individuals are prone to produce HNA-2 alloantibodies that cause a number of disorders including transfusion-related acute lung injury and immune neutropenia. In addition, the percentages of HNA-2 positive neutrophils vary significantly among individuals and HNA-2 expression variations play a role in human diseases such as myelodysplastic syndrome, chronic myelogenous leukemia, and gastric cancer. The underlying genetic mechanism of HNA-2 deficiency and expression variations has remained a mystery. In this study, we identified a novel CD177 nonsense single nucleotide polymorphism (SNP 829A>T) that creates a stop codon within the CD177 coding region. We found that all 829TT homozygous individuals were HNA-2 deficient. In addition, the SNP 829A>T genotypes were significantly associated with the percentage of HNA-2 positive neutrophils. Transfection experiments confirmed that HNA-2 expression was absent on cells expressing the CD177 SNP 829T allele. Our data clearly demonstrate that the CD177 SNP 829A>T is the primary genetic determinant for HNA-2 deficiency and expression variations. The mechanistic delineation of HNA-2 genetics will enable the development of genetic tests for diagnosis and prognosis of HNA-2-related human diseases. PMID:26024230

  20. Galectin-9 Signaling through TIM-3 Is Involved in Neutrophil-Mediated Gram-Negative Bacterial Killing: An Effect Abrogated within the Cystic Fibrosis Lung

    Science.gov (United States)

    Vega-Carrascal, Isabel; Bergin, David A.; McElvaney, Oliver J.; McCarthy, Cormac; Banville, Nessa; Pohl, Kerstin; Hirashima, Mitsuomi; Kuchroo, Vijay K.; Reeves, Emer P.; McElvaney, Noel G.

    2016-01-01

    The T cell Ig and mucin domain–containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-α exposure (p < 0.05). Our data suggest a novel role for TIM-3/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p < 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment. PMID:24477913

  1. The alteration in peripheral neutrophils of patients with chronic kidney disease

    OpenAIRE

    Yevgenyevna Muravlyova Larissa; Molotov-Luchankiy Vilen Borisovich; Yemelyevna Bakirova Ryszhan; Akylbekovna Turmukhambetova Anar; Anatolyevich Klyuyev Dmitriy; Andreevna Demidchik Ludmila; Alexandrovna Kolesnikova Yevgeniya

    2015-01-01

    Recent findings have demonstrated the impaired functions of neutrophils of patients with chronic renal failure. The purpose of our research was to study oxidative modified proteins, as well as the histone spectrum in neutrophils drawn from patients with chronic kidney disease, and to estimate the ability of neutrophils to form spontaneous neutrophil extracellular traps. In this work, we have assumed that metabolic alteration in neutrophils may develop at early stages of chronic kidney disease...

  2. Prolactin modulation of nitric oxide and TNF-alpha production by peripheral neutrophils in rats.

    Science.gov (United States)

    Meli, R; Raso, G M; Gualillo, O; Pacilio, M; Di Carlo, R

    1997-01-01

    It has been demonstrated that prolactin (PRL) is a potent immunomodulator that exerts stimulatory effects on physiological responses of immune cells. In the present research we have investigated whether PRL may influence nitric oxide (NO) and/or tumor necrosis factor-alpha (TNF-alpha) production in neutrophils obtained from inflammatory exudate of carrageenin-induced experimental pleurisy in the rat. In this acute model of inflammation the role of endogenous NO was evaluated using an inhibitor of NO-synthase, NG-nitro-L-arginine methyl ester (L-NAME). A treatment of animals with L-NAME (10 mg/kg s.c.) induced a reduction of volume and cell number of pleural exudate and a decrease of nitrite production (measured by the Griees reaction) by polymorphonuclear cells after 24 h of incubation, while D-NAME, the inactive isomer, was without effect. Neutrophils from ovine prolactin (oPRL) treated rats (5 mg/kg for 5 times s.c.) or from rats with a hyperprolactinaemia induced by pituitary gland graft produced higher amounts of NO both after 24 and 48 h of incubation. On the contrary, a clear reduction in the production of NO was found in neutrophils from rats treated with bromocriptine (BRC) (2 mg/kg s.c.), a dopamine D2-receptor agonist. TNF-alpha production (measured by MTT/cytotoxic assay) by neutrophils was markedly increased in PRL-treated or pituitary-grafted rats in comparison to controls, whereas BRC treatment reduced TNF-alpha production. PMID:9335229

  3. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.

    Science.gov (United States)

    Pelaia, Girolamo; Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa; Maselli, Rosario

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  4. Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma

    Directory of Open Access Journals (Sweden)

    Girolamo Pelaia

    2015-01-01

    Full Text Available Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments.

  5. Technical advance: immunophenotypical characterization of human neutrophil differentiation

    DEFF Research Database (Denmark)

    Mora-Jensen, Helena Isabel; Jendholm, Johan; Fossum, Anna;

    2011-01-01

    The current study reports a flow cytometry-based protocol for the prospective purification of human BM populations representing six successive stages of terminal neutrophil differentiation, including early promyelocytes and late promyelocytes, myelocytes, metamyelocytes, band cells, and PMN neutr...

  6. Oxidative burst of neutrophils against melanoma B16-F10.

    Science.gov (United States)

    Zivkovic, Morana; Poljak-Blazi, Marija; Zarkovic, Kamelija; Mihaljevic, Danijela; Schaur, Rudolf Joerg; Zarkovic, Neven

    2007-02-01

    Intensive oxidative burst was determined by chemiluminescence of peripheral blood neutrophils of mice that were intramuscularly injected with melanoma B16-F10 and/or subcutaneously with Sephadex G-200. The neutrophils from papula developed at the site of Sephadex injection were cytotoxic for the B16-F10 cells in vitro. However, survival of Sephadex injected tumour-bearing mice was lower than of control animals bearing B16-F10, while their tumours grew faster and were less necrotic. Thus, it is likely that injection of Sephadex distracted the neutrophils from the tumour allowing faster progression of the tumour, indicating that neutrophils may have an important role in the host defence against malignant cells in the early stage of tumour development. PMID:16564616

  7. A Case of Simultaneous, Biopsy-Proven, Classic, ANCA-Positive Wegener's Granulomatosis and Anti-GBM Disease, but without Detectible Circulating Anti-GBM Antibodies

    OpenAIRE

    Aleksandra Gmurczyk; Shubhada N. Ahya; Robert Goldschmidt; George Kim; L. Tammy Ho; Kevin Nash

    2010-01-01

    Wegener's granulomatosis (WG) is a systemic, necrotizing, granulomatous vasculitis of unknown etiology. Approximately 75% of cases present as classic WG with both pulmonary and renal involvement, while the remaining 25% of patients present with a limited form with either predominantly upper or lower respiratory tract symptoms. Ninety percent of WG patients have circulating anti–neutrophil cytoplasmic antibodies (ANCA), and approximately 10% have both circulating ANCA antibodies and concomitan...

  8. Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats

    Directory of Open Access Journals (Sweden)

    Koemeter-Cox Andrew I

    2011-05-01

    Full Text Available Abstract Background Exposure to the nerve agent soman (GD causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE. Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model. Methods Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells. Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines. Results We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain. Conclusions A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.

  9. The Mechanics of Neutrophils: Synthetic Modeling of Three Experiments

    OpenAIRE

    Herant, Marc; Marganski, William A; Dembo, Micah

    2003-01-01

    Much experimental data exist on the mechanical properties of neutrophils, but so far, they have mostly been approached within the framework of liquid droplet models. This has two main drawbacks: 1), It treats the cytoplasm as a single phase when in reality, it is a composite of cytosol and cytoskeleton; and 2), It does not address the problem of active neutrophil deformation and force generation. To fill these lacunae, we develop here a comprehensive continuum-mechanical paradigm of the neutr...

  10. Decreased neutrophil apoptosis in quiescent ANCA-associated systemic vasculitis.

    Directory of Open Access Journals (Sweden)

    Mohamed Abdgawad

    Full Text Available BACKGROUND: ANCA-Associated Systemic Vasculitis (AASV is characterized by leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils in perivascular tissues. Dysregulation of neutrophil cell death may contribute directly to the pathogenesis of AASV. METHODS: Neutrophils from Healthy Blood Donors (HBD, patients with AASV most in complete remission, Polycythemia Vera (PV, Systemic Lupus Erythematosus (SLE, Rheumatoid Arthritis (RA and renal transplant recipients (TP were incubated in vitro, and the rate of spontaneous apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors, transcription factors C/EBP-α, C/EBP-β and PU.1 and inhibitors of survival/JAK2-pathway were measured by real-time-PCR. RESULTS: AASV, PV and RA neutrophils had a significantly lower rate of apoptosis compared to HBD neutrophils (AASV 50 ± 14% vs. HBD 64 ± 11%, p<0.0001. In RA but not in AASV and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-α, C/EBP-β were significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS were significantly higher in AASV compared to HBD. CONCLUSION: Neutrophil apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to differ. Increased mRNA levels of granulopoiesis-associated transcription factors and increased levels of sFAS in plasma were observed in AASV. Additional studies are required to define the mechanisms behind the decreased apoptosis rates, and possible connections with accumulation of dying neutrophils in regions of vascular lesions in AASV patients.

  11. Neutrophil function and metabolism in individuals with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    T.C. Alba-Loureiro

    2007-08-01

    Full Text Available Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibilityto and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesionto the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e., glycolytic and glutaminolytic pathways may be involved in the reduction of neutrophil function observed in diabetic states. Metabolic routes by which hyperglycemia is linked to neutrophil dysfunction include the advanced protein glycosylation reaction, the polyol pathway, oxygen-free radical formation, the nitric oxide-cyclic guanosine-3'-5'monophosphate pathway, and the glycolytic and glutaminolytic pathways. Lowering of blood glucose levels by insulin treatment of diabetic patients or experimental animals has been reported to have significant correlation with improvement of neutrophil functional activity. Therefore, changes might be primarily linked to a continuing insulin deficiency or to secondary hyperglycemia occurring in the diabetic individual. Accordingly, effective control with insulin treatment is likely to be relevant during infection in diabetic patients.

  12. Effects of Acrolein on Leukotriene Biosynthesis in Human Neutrophils

    OpenAIRE

    Zemski Berry, Karin A.; Henson, Peter M.; Murphy, Robert C.

    2008-01-01

    Acrolein is a toxic, highly reactive α,β-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-LO products in addition to small amounts of COX produc...

  13. Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy

    OpenAIRE

    Chu, Dafeng; Zhao, Qi; Yu, Jian; Zhang, Faya; Zhang, Hui; Wang, Zhenjia

    2016-01-01

    Cancer immunotherapy using tumor specific monoclonal antibodies (mAbs) presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma, initiates neutrophil recruitment in tumor responsible for cancer therapy. Here we report a strategy for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, we showed that systemically delivered albumin NPs increased in tumor when TA99 antibod...

  14. Physiological Concentrations of Leptin Do Not Affect Human Neutrophils

    OpenAIRE

    Kamp, V.M.; Langereis, J.D.; Aalst, C.W. van; Linden, J.; Ulfman, L.H.; Koenderman, L.

    2013-01-01

    Leptin is an adipokine that is thought to be important in many inflammatory diseases, and is known to influence the function of several leukocyte types. However, no clear consensus is present regarding the responsiveness of neutrophils for this adipokine. In this study a 2D DIGE proteomics approach was used as an unbiased approach to identify leptin-induced effects on neutrophils. Additionally chemotaxis and survival experiments were performed to reproduce results from literature showing puta...

  15. Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis

    OpenAIRE

    Jaeger, B. N.; Donadieu, J.; Cognet, C.; Bernat, C.; Ordonez-Rueda, D.; Barlogis, V.; Mahlaoui, N.; Fenis, A.; Narni-Mancinelli, E.; Beaupain, B.; Bellanne-Chantelot, C.; Bajenoff, M.; Malissen, B.; Malissen, M; Vivier, E.

    2012-01-01

    Natural killer (NK) cells are bone marrow (BM)–derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection of this phenotype showed that mature neutrophils were required both in the BM and in the periphery for proper NK cell development. In mice lacking neutrophils, NK cells displayed hyperproliferation...

  16. Neutrophil Priming by Cytokines in Patients With Obstructive Jaundice

    OpenAIRE

    W. G. Jiang; Puntis, M. C. A.; Hallett, M B

    1994-01-01

    Patients with obstructive jaundice frequently suffer postoperative complications. We have investigated the relationship of obstructive jaundice to the neutrophil oxidase response and the “priming” of the response by the cytokines TNFα, interleukin-1 (IL-1), IL-6, and IL-8. On stimulation with f-met-leuphe (fmlp), the respiratory burst in neutrophils from jaundiced patients was greatly increased compared with controls (p < 0.01), jaundiced patients having the highest respiratory bu...

  17. Flavonoids Inhibit the Respiratory Burst of Neutrophils in Mammals

    OpenAIRE

    Milan Ciz; Petko Denev; Maria Kratchanova; Ondrej Vasicek; Gabriela Ambrozova; Antonin Lojek

    2012-01-01

    Neutrophils represent the front-line defence cells in protecting organisms against infection and play an irreplaceable role in the proper performance of the immune system. As early as within the first minutes of stimulation, neutrophilic NADPH oxidase is activated, and cells release large quantities of highly toxic reactive oxygen species (ROS). These oxidants can be highly toxic not only for infectious agents but also for neighboring host tissues. Since flavonoids exhibit antioxidant and ant...

  18. Disentangling the effects of tocilizumab on neutrophil survival and function.

    Science.gov (United States)

    Gaber, Timo; Hahne, Martin; Strehl, Cindy; Hoff, Paula; Dörffel, Yvonne; Feist, Eugen; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2016-06-01

    The synovial tissue in rheumatoid arthritis (RA) represents a hypoxic environment with up-regulated pro-inflammatory cytokines and cellular infiltrates including neutrophils. Although inhibition of the interleukin (IL)6 receptor pathway by tocilizumab is a potent treatment option for RA, it may also cause adverse effects such as an occasionally high-grade neutropenia. We analysed the impact of tocilizumab on survival, mediator secretion, oxidative burst, phagocytosis and energy availability of high-dose toll-like receptor (TLR)2/4-stimulated neutrophils (to mimic an arthritis flare) under normoxic versus hypoxic conditions. Human neutrophils were purified, pre-treated with varying doses of tocilizumab, dexamethasone or human IgG1 and high-dose-stimulated with lipopolysaccharide (LPS) alone-triggering TLR2/4-, LPS plus IL6, or left unstimulated. Cells were then incubated under normoxic (18 % O2) or hypoxic (1 % O2) conditions and subsequently analysed. Neutrophil survival and energy availability were significantly decreased by tocilizumab in a dose-dependent manner in high-dose TLR2/4-stimulated cells, but to a greater extent under normoxia as compared to hypoxia. We also found high-dose LPS-stimulated oxidative burst and phagocytosis of neutrophils to be higher under hypoxic versus normoxic conditions, but this difference was reduced by tocilizumab. Finally, we observed that tocilizumab affected neutrophil mediator secretion as a function of oxygen availability. Tocilizumab is known for both beneficial effects and a higher incidence of neutropenia when treating RA patients. Our results suggest that both effects can at least in part be explained by a reduction in neutrophil survival, a dose-dependent inhibition of hypoxia-induced NADPH oxidase-mediated oxidative burst and phagocytosis of infiltrating hypoxic neutrophils and an alteration of mediator secretion. PMID:26721805

  19. PULMONARY CIRCULATION AT EXERCISE

    OpenAIRE

    R. Naeije; CHESLER, N

    2012-01-01

    The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associ...

  20. Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody.

    Science.gov (United States)

    Yokoseki, Akiko; Saji, Etsuji; Arakawa, Musashi; Kosaka, Takayuki; Hokari, Mariko; Toyoshima, Yasuko; Okamoto, Kouichirou; Takeda, Shigeki; Sanpei, Kazuhiro; Kikuchi, Hirotoshi; Hirohata, Shunsei; Akazawa, Kouhei; Kakita, Akiyoshi; Takahashi, Hitoshi; Nishizawa, Masatoyo; Kawachi, Izumi

    2014-02-01

    The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting TH1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and

  1. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    Directory of Open Access Journals (Sweden)

    Ole H. Nielsen

    1992-01-01

    Full Text Available Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l was as potent as the calcium ionophore A23187 (10 μmol/l for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the decreases in radioactivity by 15.4% and 30.5%, respectively. The mechanism responsible for the release of arachidonate from cellular membranes is closely coupled to cellular calcium metabolism, and melittin was found to promote calcium entry through receptor gated calcium channels, probably due to an activation of phospholipase A2. Furthermore, a down-regulation of leukotriene B4 receptors was seen. The maximal number of binding sites per cell was reduced from a median of 1520 to 950 with melittin (1 μmol/l. The study has revealed some factors important for the inflammatory mechanisms mediated by melittin.

  2. Role of reverse transendothelial migration of neutrophils in inflammation.

    Science.gov (United States)

    Hirano, Yohei; Aziz, Monowar; Wang, Ping

    2016-06-01

    Transmigration of neutrophils through vascular endothelial walls into the inflamed tissues is a critical defense mechanism of innate immune system against infection and injury caused by sepsis, trauma, ischemia-reperfusion, and other acute or chronic inflammatory diseases. However, their excessive infiltration and uncontrolled activation may lead to the destruction of normal tissue architecture and unrestrained inflammation. Transendothelial migration (TEM) in a luminal-to-abluminal direction is widely known as the final step of neutrophil migration cascade into the inflamed tissues. Recent studies have shown that neutrophils not necessarily move from the vascular lumen to the extravascular tissues in a one way direction; they also proceed in an opposite direction, known as reverse transendothelial migration (rTEM) to get back into the vascular lumen again. This novel paradigm of neutrophil round trip is currently on the spotlight due to its possible interaction with immune system. Current review highlighting the growing demand of this newly identified neutrophil migratory event will not only rewrite the disease pathophysiology, but also help scientists design novel therapeutic strategy leading to the remission of inflammatory diseases in which controlling exaggerated neutrophil infiltration is a major challenge. PMID:26872312

  3. Effect of Prototheca zopfii on neutrophil function from bovine milk.

    Science.gov (United States)

    Cunha, Luciane T; Pugine, Silvana P; Valle, Claudia R; Ribeiro, Andrea R; Costa, Ernane J X; De Melo, Mariza P

    2006-12-01

    This study was carried to investigate neutrophil function in the presence of Prototheca zopfii. For this purpose, bovine milk neutrophils were incubated in the absence (control) of and presence of P. zopfii, and then they were examined hydrogen peroxide (H(2)O(2)) production, antioxidant enzyme activities, and phagocytic capacity. Milk was collected from negative "California Mastitis Test" (CMT) quarter from three lactating Holstein cows after induction of leukocytosis with an intramammary infusion of oyster glycogen. H(2)O(2) production was measured using the phenol red method. Catalase activity was measured following H(2)O(2) reduction at 240 nm and the activity of glutathione reductase was determined by measuring the rate of NADPH oxidation at 340 nm. P. zopfii death was assessed by fluorescent microscopy using acridine orange assay and by colony forming units (CFUs). Comparisons between the groups were initially performed by analysis of variance (ANOVA). Significant differences were then compared using Tukey's test with a significance coefficient of 0.05. Hydrogen peroxide production, catalase and glutathione reductase activities by neutrophils incubated in presence of P. zopfii were stimulated five times, 21% and 27% respectively, compared to the unstimulated-neutrophils. Neutrophils did not affect P. zopfii death as shown by microscopy and CFUs. These observations led to the conclusion that the P. zopfii promote a high increase of H(2)O(2) production by neutrophils from bovine milk during algae exposition accompanied by increase of antioxidant enzyme activities; however, this process did not affect P. zopfii death. PMID:17146586

  4. Free p-Cresol Alters Neutrophil Function in Dogs.

    Science.gov (United States)

    Bosco, Anelise Maria; Pereira, Priscila Preve; Almeida, Breno Fernando Martins; Narciso, Luis Gustavo; Dos Santos, Diego Borba; Santos-Neto, Álvaro José Dos; Ferreira, Wagner Luis; Ciarlini, Paulo César

    2016-05-01

    To achieve a clearer understanding of the mechanisms responsible for neutrophil dysfunction recently described in dogs with chronic renal failure (CRF), the plasma concentrations of free p-cresol in healthy dogs (n = 20) and those with CRF (n = 20) were compared. The degree of correlation was determined between plasma levels of p-cresol and markers of oxidative stress and function of neutrophils in these dogs. The effect of this compound on oxidative metabolism and apoptosis was assessed in neutrophils isolated from 16 healthy dogs incubated in RPMI 1640 supplemented with p-cresol (0.405 mg/L) and compared with medium supplemented with uremic plasma (50%). To achieve this, the plasma concentration of p-cresol was quantified by liquid phase high-performance liquid chromatography. The neutrophil oxidative metabolism was determined using the probes hydroethidine and 2',7'-dichlorofluorescein diacetate and apoptosis was measured using Annexin V-PE by capillary flow cytometry. Compared with the healthy dogs, uremic dogs presented higher concentrations of free p-cresol, greater oxidative stress, and neutrophils primed for accelerated apoptosis. The free p-cresol induced in neutrophils from healthy dogs increased apoptosis and decreased reactive oxygen species production. We conclude that the health status presented during uremia concomitant with the increase in plasma free p-cresol can contribute to the presence of immunosuppression in dogs with CRF. PMID:26496142

  5. Neutrophil migration into the placenta: Good, bad or deadly?

    Science.gov (United States)

    Giaglis, Stavros; Stoikou, Maria; Grimolizzi, Franco; Subramanian, Bibin Y.; van Breda, Shane V.; Hoesli, Irene; Lapaire, Olav; Hasler, Paul; Than, Nandor Gabor; Hahn, Sinuhe

    2016-01-01

    ABSTRACT Almost 2 decades have passed since the discovery that pregnancy is associated with a basal inflammatory state involving neutrophil activation, and that this is more overt in cases with preeclampsia, than in instances with sepsis. This pivotal observation paved the way for our report, made almost a decade ago, describing the first involvement of neutrophil extracellular traps (NETs) in a non-infectious human pathology, namely preeclampsia, where an abundance of these structures were detected directly in the placental intervillous space. Despite these remarkable findings, there remains a paucity of interest among reproductive biologists in further exploring the role or involvement of neutrophils in pregnancy and related pathologies. In this review we attempt to redress this deficit by highlighting novel recent findings including the discovery of a novel neutrophil subset in the decidua, the interaction of placental protein 13 (PP13) and neutrophils in modulating spiral artery modification, as well as the use of animal model systems to elucidate neutrophil function in implantation, gestation and parturition. These model systems have been particularly useful in identifying key components implicated in recurrent fetal loss, preeclampsia or new signaling molecules such as sphingolipids. Finally, the recent discovery that anti-phospolipid antibodies can trigger NETosis, supports our hypothesis that these structures may contribute to placental dysfunction in pertinent cases with recurrent fetal loss. PMID:26933824

  6. Cinnoline derivatives as human neutrophil elastase inhibitors.

    Science.gov (United States)

    Giovannoni, Maria Paola; Schepetkin, Igor A; Crocetti, Letizia; Ciciani, Giovanna; Cilibrizzi, Agostino; Guerrini, Gabriella; Khlebnikov, Andrei I; Quinn, Mark T; Vergelli, Claudia

    2016-08-01

    Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195. PMID:26194018

  7. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  8. Differential Surface Expression of CD18 and CD44 by Neutrophils in Bone Marrow and Spleen Contributed to the Neutrophilia in Thalidomide-treated Female B6C3F1 Mice1

    OpenAIRE

    Auttachoat, Wimolnut; Zheng, Jian Feng; Chi, Rui P.; Meng, Andrew; Guo, Tai L.

    2006-01-01

    Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lung of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14...

  9. Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils.

    Directory of Open Access Journals (Sweden)

    Zvi G Fridlender

    Full Text Available The role of myeloid cells in supporting cancer growth is well established. Most work has focused on myeloid-derived suppressor cells (MDSC that accumulate in tumor-bearing animals, but tumor-associated neutrophils (TAN are also known to be capable of augmenting tumor growth. However, little is known about their evolution, phenotype, and relationship to naïve neutrophils (NN and to the granulocytic fraction of MDSC (G-MDSC.In the current study, a transcriptomics approach was used in mice to compare these cell types. Our data show that the three populations of neutrophils are significantly different in their mRNA profiles with NN and G-MDSC being more closely related to each other than to TAN. Structural genes and genes related to cell-cytotoxicity (i.e. respiratory burst were significantly down-regulated in TAN. In contrast, many immune-related genes and pathways, including genes related to the antigen presenting complex (e.g. all six MHC-II complex genes, and cytokines (e.g. TNF-α, IL-1-α/β, were up-regulated in G-MDSC, and further up-regulated in TAN. Thirteen of the 25 chemokines tested were markedly up-regulated in TAN compared to NN, including striking up-regulation of chemoattractants for T/B-cells, neutrophils and macrophages.This study characterizes different populations of neutrophils related to cancer, pointing out the major differences between TAN and the other neutrophil populations.

  10. Fluctuation Theorem in an Atmospheric Circulation Model

    CERN Document Server

    Schalge, Bernd; Wouters, Jeroen; Fraedrich, Klaus; Lunkeit, Frank

    2012-01-01

    Evidence for the validity of the Fluctuation Theorem (FT) in an atmospheric Global Circulation Model is found. The model is hydrostatic with variable numbers of vertical levels and different horizontal resolutions. For finite time intervals the largest local Lyapunov exponent (LLLE) is found to be negative consistent with predictions of the FT. The effect is present for resolutions up to wave numbers l=42 (~ 250km) and 10 levels.

  11. Human neutrophils and oral microbiota: a constant tug-of-war between a harmonious and a discordant coexistence.

    Science.gov (United States)

    Uriarte, Silvia M; Edmisson, Jacob S; Jimenez-Flores, Emeri

    2016-09-01

    Neutrophils are a major component of the innate host response, and the outcome of the interaction between the oral microbiota and neutrophils is a key determinant of oral health status. The composition of the oral microbiome is very complex and different in health and disease. Neutrophils are constantly recruited to the oral cavity, and their protective role is highlighted in cases where their number or functional responses are impeded, resulting in different forms of periodontal disease. Periodontitis, one of the more severe and irreversible forms of periodontal disease, is a microbial-induced chronic inflammatory disease that affects the gingival tissues supporting the tooth. This chronic inflammatory disease is the result of a shift of the oral bacterial symbiotic community to a dysbiotic more complex community. Chronic inflammatory infectious diseases such as periodontitis can occur because the pathogens are able to evade or disable the innate immune system. In this review, we discuss how human neutrophils interact with both the symbiotic and the dysbiotic oral community; an understanding of which is essential to increase our knowledge of the periodontal disease process. PMID:27558341

  12. Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    2014-01-01

    Full Text Available We demonstrate that high mobility group box 1 protein (HMGB1 directs Th17 skewing by regulating dendritic cell (DC function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1 activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretion in vivo by using a murine model of neutrophilic asthma induced by ovalbumin (OVA plus lipopolysaccharide (LPS. Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C+ APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma.

  13. Maturation arrest of neutrophils-a possible reason for the leucopenia in sodium selenite induced sub-chronic selenosis in cow calves.

    Science.gov (United States)

    Rampal, Satyavan; Kumar, Rakesh; Randhawa, Charanjit S; Sood, Naresh

    2008-01-01

    The effect of long-term administration of sodium selenite on leucocyte indices of peripheral blood of calves was determined. Nine calves, 9-12 months old, with an average body weight of 104kg were divided into three groups. Calves of groups 2 and 3 were administered with sodium selenite at 0.1 and 0.25mg/kg body weight for 98 consecutive days. The clinical signs characteristic of selenosis viz. alopecia, cracking of hooves, intradigital lesions and discoloration of hard palate, started appearing from 45 to 60 days onwards with high dose, whereas only subtle indications of toxicosis were observed in the low-dose group. The prolonged administration of sodium selenite produced a progressive and dose-dependent decline in the circulating leucocyte count with concomitant decline in the circulating neutrophil count. There was a high negative correlation (0.94) between blood selenium levels and neutrophils. Granulocyte/agranulocyte ratio was also significantly reduced in the treated animals. Evaluation of bone marrow smears revealed a decline in the myeloid to erythroid ratio. In addition, there was also maturation arrest of neutrophils at promyelocyte or myelocyte level as shown by differential granulocyte count in the bone marrow. The results indicated that host's immune response may be adversely affected. PMID:21783834

  14. Neutrophil labeling with [{sup 99m}Tc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, Hayley [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ramsay, Stuart C. [School of Medicine, James Cook University, Townsville, Queensland (Australia) and Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia)]. E-mail: stuart.ramsey@jcu.edu.au; Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Cassidy, Nathan [Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland (Australia)

    2006-04-15

    Introduction: [{sup 99m}Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.

  15. Neutrophil labeling with [99mTc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

    International Nuclear Information System (INIS)

    Introduction: [99mTc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection

  16. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin

    Science.gov (United States)

    Konstantopoulos, K.; Neelamegham, S.; Burns, A. R.; Hentzen, E.; Kansas, G. S.; Snapp, K. R.; Berg, E. L.; Hellums, J. D.; Smith, C. W.; McIntire, L. V.; Simon, S. I.

    1998-01-01

    BACKGROUND: After activation, platelets adhere to neutrophils via P-selectin and beta2-integrin. The molecular mechanisms and adhesion events in whole blood exposed to venous levels of hydrodynamic shear in the absence of exogenous activation remain unknown. METHODS AND RESULTS: Whole blood was sheared at approximately 100 s(-1). The kinetics of neutrophil-platelet adhesion and neutrophil aggregation were measured in real time by flow cytometry. P-selectin was upregulated to the platelet surface in response to shear and was the primary factor mediating neutrophil-platelet adhesion. The extent of neutrophil aggregation increased linearly with platelet adhesion to neutrophils. Blocking either P-selectin, its glycoprotein ligand PSGL-1, or both simultaneously by preincubation with a monoclonal antibody resulted in equivalent inhibition of neutrophil-platelet adhesion (approximately 30%) and neutrophil aggregation (approximately 70%). The residual amount of neutrophil adhesion was blocked with anti-CD11b/CD18. Treatment of blood with prostacyclin analogue ZK36374, which raises cAMP levels in platelets, blocked P-selectin upregulation and neutrophil aggregation to baseline. Complete abrogation of platelet-neutrophil adhesion required both ZK36374 and anti-CD18. Electron microscopic observations of fixed blood specimens revealed that platelets augmented neutrophil aggregation both by forming bridges between neutrophils and through contact-mediated activation. CONCLUSIONS: The results are consistent with a model in which venous levels of shear support platelet adherence to neutrophils via P-selectin binding PSGL-1. This interaction alone is sufficient to mediate neutrophil aggregation. Abrogation of platelet adhesion and aggregation requires blocking Mac-1 in addition to PSGL-1 or P-selectin. The described mechanisms are likely of key importance in the pathogenesis and progression of thrombotic disorders that are exacerbated by leukocyte-platelet aggregation.

  17. In vivo suppressive effect of nuclear factor-κB inhibitor on neutrophilic inflammation of grafts after orthotopic liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Gu; Yu-Dong Qiu; Fu-Tao Xu; Yong Jiang; Yi-Tao Ding

    2004-01-01

    AIM: To investigate the effect of pyrrolidine dithiocarbamate (PDTC), a novel nuclear factor-κB (NF-κB) inhibitor, on expression of multiple inflammatory mediators and neutrophilic inflammation of cold preserved grafts after rat liver transplantation and its significance.METHODS: Orthotopic liver transplantation (OLT) was performed after 24 h of cold storage using University of Wisconsin solution with varied concentrations of PDTC. We determined the time course of NF-κB activation and expression of multiple inflammatory signals, such as tumor necrosis factor-α (TNF-α), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1(ICAM-1) by ElISA methods. Serum alanine aminotransferase (ALT), intrahepatic myeloperoxidase (MPO)/WBC (ameasure of neutrophil accumulation) and Mac-1 expression (a measure of circulating neutrophil activity) were also evaluated.RESULTS: PDTC decreased NF-κB activation induced by prolonged cold preservation in a dose dependent manner (from 20 mmol/L to 60 mmol/L), diminished TNF-α, CINC, ICAM-1 proteins in the grafts, and reduced the expression of increases in plasma TNF-α levels induced by prolonged cold preservation. Neutrophilic inflammation of the graft was significantly suppressed after preservation with PDTC (P<0.05). The total neutrophil accumulation in PDTC (40 mmol/L) group (7.04±0.97) was markedly reduced compared to control group (14.07±1.31) (P<0.05). Mac-1expression was significantly reduced in PDTC (40 mmol/L)group (181±11.3%) compared with the control group (281±13.2%) (P<0.05) at 6 h after reperfusion. Furthermore,PDTC inhibited the increased serum ALT levels after liver transplantation.CONCLUSION: PDTC can inhibit B NF-κB activation and expression of the inflammatory mediators, which are associated with improved graft viability via inhibiting intrahepatic neutrophilic inflammation. Our study suggests that a therapeutic strategy directed at inhibition of NF-κB activation in the

  18. On Skew Circulant Type Matrices Involving Any Continuous Fibonacci Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    inverse matrices of them by constructing the transformation matrices. Furthermore, the maximum column sum matrix norm, the spectral norm, the Euclidean (or Frobenius norm, and the maximum row sum matrix norm and bounds for the spread of these matrices are given, respectively.

  19. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors

    DEFF Research Database (Denmark)

    Damgaard, C; Kantarci, A; Holmstrup, P; Hasturk, H; Nielsen, Claus Henrik; Van Dyke, T E

    2016-01-01

    BACKGROUND AND OBJECTIVES: Porphyromonas gingivalis is regarded as a significant contributor in the pathogenesis of periodontitis and certain systemic diseases, including atherosclerosis. P. gingivalis occasionally translocates from periodontal pockets into the circulation, where it adheres to red...... (ROS) in response to challenge with P. gingivalis. In addition, the impact of RBC interaction with P. gingivalis was investigated. The actions of resolvin E1 (RvE1), a known regulator of P. gingivalis induced neutrophil responses, on the cytokine and ROS responses elicited by P. gingivalis in cultures...... of neutrophils were investigated. RESULTS: Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically...

  20. Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

    International Nuclear Information System (INIS)

    Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lungs of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14 days increased the percentage and the number of neutrophils in the spleen in the first 8 h (peaking at 2 h) after the last Thd treatment, and it returned to the baseline after 24 h. However, Thd treatment for 28 days increased the percentage and number of neutrophils in the spleen even at the 24-h time point after the last Thd treatment. These neutrophils were demonstrated to be functional by the myeloperoxidase activity assay. Further studies have ruled out the possibility of an increased bone marrow granulopoiesis following Thd treatment. Flow cytometric analysis of the surface expression of adhesion molecules suggested that Thd treatment for either 14 or 28 days decreased the surface expression of either CD18 or CD44 by bone marrow neutrophils. On the other hand, the surface expression of both CD18 and CD44 by splenic neutrophils was increased following Thd treatment for 28 days but not for 14 days. No effect was produced for other cell surface molecules such as CD62L and CD11a. It was possible that decreased surface expressions of CD18 and CD44 facilitated neutrophils' release from the bone marrow; increased surface expressions of CD44 and CD18 by splenic neutrophils after 28 days of Thd treatment increased their ability to remain in the periphery. Taken together, Thd treatment increased neutrophils in female B6C3F1 mice, at least partially, through differentially modulating the surface expression of CD18 and CD44 by the neutrophils in the bone marrow and spleen

  1. Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice.

    Science.gov (United States)

    Auttachoat, Wimolnut; Zheng, Jian Feng; Chi, Rui P; Meng, Andrew; Guo, Tai L

    2007-02-01

    Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lungs of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14 days increased the percentage and the number of neutrophils in the spleen in the first 8 h (peaking at 2 h) after the last Thd treatment, and it returned to the baseline after 24 h. However, Thd treatment for 28 days increased the percentage and number of neutrophils in the spleen even at the 24-h time point after the last Thd treatment. These neutrophils were demonstrated to be functional by the myeloperoxidase activity assay. Further studies have ruled out the possibility of an increased bone marrow granulopoiesis following Thd treatment. Flow cytometric analysis of the surface expression of adhesion molecules suggested that Thd treatment for either 14 or 28 days decreased the surface expression of either CD18 or CD44 by bone marrow neutrophils. On the other hand, the surface expression of both CD18 and CD44 by splenic neutrophils was increased following Thd treatment for 28 days but not for 14 days. No effect was produced for other cell surface molecules such as CD62L and CD11a. It was possible that decreased surface expressions of CD18 and CD44 facilitated neutrophils' release from the bone marrow; increased surface expressions of CD44 and CD18 by splenic neutrophils after 28 days of Thd treatment increased their ability to remain in the periphery. Taken together, Thd treatment increased neutrophils in female B6C3F1 mice, at least partially, through differentially modulating the surface expression of CD18 and CD44 by the neutrophils in the bone marrow and spleen. PMID

  2. INTERNAL CIRCULATION ENVELOPES

    CERN Multimedia

    Mail Office

    2001-01-01

    Internal mail envelopes often finish up in large piles in certain offices, thus creating a shortage for other users of the mail service, who would be grateful if everyone with an unused stock could deposit them in their mail box, after attaching them together with an elastic band or a piece of string. The messengers will then collect them so that the Mail Office can put them back in circulation. Thank you for your understanding and collaboration.

  3. Nitrite attenuated peroxynitrite and hypochlorite generation in activated neutrophils.

    Science.gov (United States)

    Ren, Xiaoming; Ding, Yun; Lu, Naihao

    2016-03-15

    Oxidative stress is usually considered as an important factor to the pathogenesis of various diseases. Peroxynitrite (ONOO(-)) and hypochlorite (OCl(-)) are formed in immune cells as a part of the innate host defense system, but excessive reactive oxygen species generation can cause progressive inflammation and tissue damage. It has been proven that through mediating nitric oxide (NO) homeostasis, inorganic nitrite (NO2(-)) shows organ-protective effects on oxidative stress and inflammation. However, the effects of NO2(-) on the function of immune cells were still not clear. The potential role of NO2(-) in modulating ONOO(-) and OCl(-) generation in neutrophil cells was investigated in this study. As an immune cell activator, lipopolysaccharide (LPS) increased both ONOO(-) and OCl(-) production in neutrophils, which was significantly attenuated by NO2(-). NO2(-) reduced superoxide (O2(·-)) generation via a NO-dependent mechanism and increased NO formation in activated neutrophils, suggesting a crucial role of O2(·-) in NO2(-)-mediated reduction of ONOO(-). Moreover, the reduced effect of NO2(-) on OCl(-) production was attributed to that NO2(-) reduced H2O2 production in activated neutrophils without influencing the release of myeloperoxidase (MPO), thus limiting OCl(-) production by MPO/H2O2 system. Therefore, NO2(-) attenuates ONOO(-) and OCl(-) formation in activated neutrophils, opening a new direction to modulate the inflammatory response. PMID:26854590

  4. Demodex-associated bacterial proteins induce neutrophil activation.

    LENUS (Irish Health Repository)

    2012-02-01

    Background: Patients with rosacea demonstrate a higher density of Demodex mites in their skin than controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea thus suggesting a possible role for bacterial proteins in the etiology of this condition. Objectives: To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. Methods: Bacterial cells were lysed and proteins were partially purified by AKTA-FPLC. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. Results: Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of MMP-9, an enzyme known to degrade collagen and cathelicidin, an antimicrobial peptide. In addition neutrophils exposed to the bacterial proteins demonstrated elevated rates of Il-8 and TNF-alpha production. Conclusions: Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea.

  5. Characterizing asthma from a drop of blood using neutrophil chemotaxis.

    Science.gov (United States)

    Sackmann, Eric Karl-Heinz; Berthier, Erwin; Schwantes, Elizabeth A; Fichtinger, Paul S; Evans, Michael D; Dziadzio, Laura L; Huttenlocher, Anna; Mathur, Sameer K; Beebe, David J

    2014-04-22

    Asthma is a chronic inflammatory disorder that affects more than 300 million people worldwide. Asthma management would benefit from additional tools that establish biomarkers to identify phenotypes of asthma. We present a microfluidic solution that discriminates asthma from allergic rhinitis based on a patient's neutrophil chemotactic function. The handheld diagnostic device sorts neutrophils from whole blood within 5 min, and generates a gradient of chemoattractant in the microchannels by placing a lid with chemoattractant onto the base of the device. This technology was used in a clinical setting to assay 34 asthmatic (n = 23) and nonasthmatic, allergic rhinitis (n = 11) patients to establish domains for asthma diagnosis based on neutrophil chemotaxis. We determined that neutrophils from asthmatic patients migrate significantly more slowly toward the chemoattractant compared with nonasthmatic patients (P = 0.002). Analysis of the receiver operator characteristics of the patient data revealed that using a chemotaxis velocity of 1.55 μm/min for asthma yields a diagnostic sensitivity and specificity of 96% and 73%, respectively. This study identifies neutrophil chemotaxis velocity as a potential biomarker for asthma, and we demonstrate a microfluidic technology that was used in a clinical setting to perform these measurements. PMID:24711384

  6. Peptide secreted by human alveolar macrophages releases neutrophil granule contents

    International Nuclear Information System (INIS)

    A monoclonal antibody was developed against an 8000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose, and by autoradiography. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-γ, tumor necrosis factor, or interleukin lα or 1β. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes

  7. Marine Natural Product Inhibitors of Neutrophil-Associated Inflammation

    Science.gov (United States)

    Chen, Chun-Yu; Tsai, Yung-Fong; Chang, Wen-Yi; Yang, Shun-Chin; Hwang, Tsong-Long

    2016-01-01

    Neutrophils are widely recognized to play an important role in acute inflammatory responses, and recent evidence has expanded their role to modulating chronic inflammatory and autoimmune diseases. Reactive oxygen species (ROS) and microbicidal compounds released from neutrophils that are recruited to the site of inflammation contribute to the pathogenesis of multiple inflammation-associated diseases such as chronic obstructive pulmonary disease, atherosclerosis, and hepatitis. Marine organisms are a valuable source of bioactive compounds with potential for industrial and pharmaceutical application. Marine natural products that inhibit neutrophil activation could be used as drugs for the treatment of inflammatory diseases. Numerous studies investigating marine natural products have reported novel anti-inflammatory agents. Nevertheless, the detailed mechanisms underlying their actions, which could facilitate our understanding of the molecular events occurring in neutrophils, have not been reported in most of the associated research studies. Therefore, in this review, we will present marine products that inhibit neutrophil-associated inflammation. Furthermore, we will be limiting the detailed discussion to agents with well-investigated molecular targets. PMID:27472345

  8. Burn injury reduces neutrophil directional migration speed in microfluidic devices.

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

  9. CXCL5 Drives Neutrophil Recruitment in TH17-Mediated GN

    Science.gov (United States)

    Disteldorf, Erik M.; Krebs, Christian F.; Paust, Hans-Joachim; Turner, Jan-Eric; Nouailles, Geraldine; Tittel, André; Meyer-Schwesinger, Catherine; Stege, Gesa; Brix, Silke; Velden, Joachim; Wiech, Thorsten; Helmchen, Udo; Steinmetz, Oliver M.; Peters, Anett; Bennstein, Sabrina B.; Kaffke, Anna; Llanto, Chrystel; Lira, Sergio A.; Mittrücker, Hans-Willi; Stahl, Rolf A.K.; Kurts, Christian; Kaufmann, Stefan H.E.

    2015-01-01

    Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in TH17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen- and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic TH17/IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in TH17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens. PMID:24904089

  10. Neutrophils in Tuberculosis: will the code be unlocked?

    Directory of Open Access Journals (Sweden)

    K Karthik

    2013-04-01

    Full Text Available Tuberculosis is a devastating disease throughout the world both in humans and animals. Its history is vast, which dates back to era of Robert Koch. There is a huge amount of immunological studies in the aspect of tuberculosis but there remain many unanswered questions. Neutrophils, cells of First line defence are being neglected in tuberculosis. Macrophages are considered as the key player in case of tuberculosis. Researches reveal that neutrophils play some interesting roles; it can be called as a bi-directional weapon. It plays instrumental role in killing mycobacterium, recruiting macrophages and also works hand in hand with macrophages in order halt the spread of the organism. Neutrophils also activates innate immunity, secretes some substances like ectosomes, which favour in trapping the mycobacterial organisms. Whether neutrophils drills the mycobacterium or gets succumbed to it depends on the stage of infection. Neutrophils at times act like a suicidal bomber, by carrying the organisms to different organs and spreading the infections. In chronic cases they are also implicated to granuloma formation, the classic sign of TB. [Vet World 2013; 6(2.000: 118-121

  11. Entamoeba histolytica induces human neutrophils to form NETs.

    Science.gov (United States)

    Ventura-Juarez, J; Campos-Esparza, Mr; Pacheco-Yepez, J; López-Blanco, J A; Adabache-Ortíz, A; Silva-Briano, M; Campos-Rodríguez, R

    2016-08-01

    Entamoeba histolytica invades the intestine and other organs during the pathogenesis of amoebiasis. In the early stages, the host organism responds with an inflammatory infiltrate composed mostly of neutrophils. It has been reported that these immune cells, activated by E. histolytica, exert a protective role by releasing proteolytic enzymes and generating reactive oxygen/nitrogen species (ROS/RNS) and antimicrobial peptides. It is now known that neutrophils also produce neutrophil extracellular traps (NETs), which are able to damage and kill pathogens. Studies have shown that intracellular protozoan pathogens, including Toxoplasma gondi, Plasmodium falciparum and Leishmania spp, induce neutrophils to release NETs and are damaged by them. However, the action of this mechanism has not been explored in relation to E. histolytica trophozoites. Through scanning electron, epifluorescence microscopy and viability assays, we show for first time that during in vitro interaction with E. histolytica trophozoites, human neutrophils released NETs that covered amoebas and reduced amoebic viability. These NETs presented histones, myeloperoxidase and decondensed chromatin. The results suggest that NETs participate in the elimination of the parasite. PMID:27138813

  12. Dynamics of circulation of the waters around India

    Digital Repository Service at National Institute of Oceanography (India)

    Shetye, S.R.

    During the last decade the understanding of dynamics of the large-scale seasonal coastal currents around India has markedly improved. However, a number of major issues concerning circulation on the shelf and in the estuaries remain unresolved...

  13. The generation of floor plans with circulation spaces

    OpenAIRE

    I Baybars

    1982-01-01

    Floor plans with interior courtyards, circulation spaces, and prespecified number of exterior rooms, are generated. The approach is graph theoretic, that is, underlying graphs are generated and, then, based on those graphs, the floor plans are constructed.

  14. On the Harmonic and Hyperharmonic Fibonacci Numbers

    OpenAIRE

    Tuglu, Naim; Kızılateş, Can; Kesim, Seyhun

    2015-01-01

    In this paper, we study the theory of the harmonic and the hyperharmonic Fibonacci numbers. Also, we get some combinatoric identities like as harmonic and hyperharmonic numbers and we obtain some useful formulas for $\\mathbb{F}_{n}$, which is finite sums of reciprocals of Fibonacci numbers. We obtain spectral and Euclidean norms of circulant matrices involving harmonic and hyperharmonic Fibonacci numbers.

  15. Case of invasive nontypable Haemophilus influenzae respiratory tract infection with a large quantity of neutrophil extracellular traps in sputum

    Directory of Open Access Journals (Sweden)

    Hamaguchi S

    2012-12-01

    Full Text Available Shigeto Hamaguchi,1,* Masafumi Seki,1,* Norihisa Yamamoto,1 Tomoya Hirose,2 Naoya Matsumoto,2 Taro Irisawa,2 Ryosuke Takegawa,2 Takeshi Shimazu,2 Kazunori Tomono11Division of Infection Control and Prevention, 2Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan *These authors contributed equally to this workAbstract: Haemophilus influenzae type b was once the most common cause of invasive H. influenzae infection, but the incidence of this disease has decreased markedly with introduction of conjugate vaccines to prevent the disease. In contrast, the incidence of invasive infection caused by nontypable H. influenzae has increased in the US and in European countries. Neutrophil extracellular traps (NETs are fibrous structures released extracellularly from activated neutrophils during inflammation, including in pneumonia, and rapidly trap and kill pathogens as a first line of immunological defense. However, their function and pathological role have not been fully investigated. Here, we report a case of fatal nontypable H. influenzae infection with severe pneumonia and bacteremia in an adult found to have a vast amount of NETs in his sputum. The patient had a two-day history of common cold-like symptoms and was taken to the emergency room as a cardiopulmonary arrest. He recovered temporarily, but died soon afterwards, although appropriate antibiotic therapy and general management had been instituted. Massive lobular pneumonia and sepsis due to nontypable H. influenzae was found, in spite of H. influenzae type b vaccine being available. His sputum showed numerous bacteria phagocytosed by neutrophils, and immunohistological staining indicated a number of NETs containing DNA, histone H3, and neutrophil elastase. This case highlights an association between formation of NETs and severe respiratory and septic infection. An increase in severe nontypable H. influenzae disease can be expected as a

  16. Hagen number versus Bejan number

    Directory of Open Access Journals (Sweden)

    Awad Mohamed M.

    2013-01-01

    Full Text Available This study presents Hagen number vs. Bejan number. Although their physical meaning is not the same because the former represents the dimensionless pressure gradient while the latter represents the dimensionless pressure drop, it will be shown that Hagen number coincides with Bejan number in cases where the characteristic length (l is equal to the flow length (L. Also, a new expression of Bejan number in the Hagen-Poiseuille flow will be introduced. At the end, extending the Hagen number to a general form will be presented. For the case of Reynolds analogy (Pr = Sc = 1, all these three definitions of Hagen number will be the same.

  17. Periodontal Manifestations of Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE) Syndrome in an 11 Year Old Patient

    OpenAIRE

    McKenna, Gerald J; Ziada, Hassan M.

    2015-01-01

    Introduction: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) is an auto inflammatory syndrome caused by an autosomal recessive gene mutation. This very rare syndrome has been reported in only 14 patients worldwide. A number of clinical signs have been reported including joint contractures, muscle atrophy, microcytic anaemia, and panniculitis-induced childhood lipodystrophy. Further symptoms include recurrent fevers, purpuric skin lesions, periorb...

  18. Superoxide Production in Galleria mellonella Hemocytes: Identification of Proteins Homologous to the NADPH Oxidase Complex of Human Neutrophils

    OpenAIRE

    Bergin, David; Reeves, Emer P.; Renwick, Julie; Wientjes, Frans B.; Kavanagh, Kevin

    2005-01-01

    The insect immune response has a number of structural and functional similarities to the innate immune response of mammals. The objective of the work presented here was to establish the mechanism by which insect hemocytes produce superoxide and to ascertain whether the proteins involved in superoxide production are similar to those involved in the NADPH oxidase-induced superoxide production in human neutrophils. Hemocytes of the greater wax moth (Galleria mellonella) were shown to be capable ...

  19. Radiation-induced muscositis and neutrophil granulocytes in oral mucosa; Strahleninduzierte Mukositis und neutrophile Granulozyten in der Mundschleimhaut

    Energy Technology Data Exchange (ETDEWEB)

    Schmidberger, H.; Rave-Fraenk, M.; Kim, S.; Hille, A.; Pradier, O.; Hess, C.F. [Klinik fuer Strahlentherapie und Radioonkologie, Univ. Goettingen (Germany)

    2003-10-01

    Background: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. Patients and Methods: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. Results: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. Conclusions: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated. (orig.) [German] Hintergrund: Die chemotherapieinduzierte Mukositis kann mit einer Verarmung der Mundschleimhaut an neutrophilen Granulozyten vergesellschaftet sein. Wir ueberprueften den Zusammenhang zwischen der radiogenen Mukositis und der Anzahl neutrophiler Granulozyten. Patienten und Methoden: Bei zehn Patienten mit Tumoren der Kopf-Hals-Region, die sich einer Strahlentherapie unterzogen, wurde die Anzahl enoraler neutrophiler

  20. Pentagonal numbers

    OpenAIRE

    Lužnik, Polona

    2013-01-01

    My graduate thesis contains a detailed examination of pentagonal nubers. In the beginning, I concentrate on figurate numbers and the mathematicians, who were the first to describe them. The work includes the basic characteristis of pentagonal numbers, how we can obtain them through calculating and counting of dots in graphic illustrtions and how we are able to check if a certain prime number is a pentagonal number or not.

  1. Adhesion receptors as therapeutic targets for circulating tumor cells

    Directory of Open Access Journals (Sweden)

    MichaelR.King

    2012-07-01

    Full Text Available Metastasis contributes to >90% of cancer-associated mortality. Though primary tumors can be removed by surgical resection or chemo/radiotherapy, metastatic disease is a great challenge to treatment due to its systemic nature. As metastatic “seeds”, circulating tumor cells (CTCs are believed to be responsible for dissemination from a primary tumor to anatomically distant organs. Despite the possibility of physical trapping of CTCs in microvessels, recent advances have provided insights into the involvement of a variety of adhesion molecules on CTCs. Such adhesion molecules facilitate direct interaction with the endothelium in specific tissues or indirectly through leukocytes. Importantly, significant progress has been made in understanding how these receptors confer enhanced invasion and survival advantage during hematogenous circulation of CTCs through recruitment of macrophages, neutrophils, platelets, and other cells. This review highlights the identification of novel adhesion molecules and how blocking their function can compromise successful seeding and colonization of CTCs in new microenvironment. Encouraged by existing diagnostic tools to identify and isolate CTCs, strategic targeting of these adhesion molecules to deliver conventional chemotherapeutics or novel apoptotic signals is discussed for the neutralization of CTCs in the circulation.

  2. Leftist Numbers

    Science.gov (United States)

    Rich, Andrew

    2008-01-01

    The leftist number system consists of numbers with decimal digits arranged in strings to the left, instead of to the right. This system fails to be a field only because it contains zerodivisors. The same construction with prime base yields the p-adic numbers.

  3. Proth Numbers

    Directory of Open Access Journals (Sweden)

    Schwarzweller Christoph

    2015-02-01

    Full Text Available In this article we introduce Proth numbers and prove two theorems on such numbers being prime [3]. We also give revised versions of Pocklington’s theorem and of the Legendre symbol. Finally, we prove Pepin’s theorem and that the fifth Fermat number is not prime.

  4. Oxidative product formation in irradiated neutrophils. A flow cytometric analysis

    International Nuclear Information System (INIS)

    The effect of irradiation on neutrophil oxidative function was evaluated using a flow cytometric assay of intracellular hydrogen peroxide (H2O2) production. This assay quantitates the H2O2-dependent conversion of the nonfluorescent compound, 2'-7'-dichlorofluorescein (DCFH), into fluorescent 2'-7'-dichlorofluorescein (DCF) on a single-cell basis. Intracellular H2O2 production in response to stimulation with phorbol myristate acetate was not affected by neutrophil irradiation at doses up to 2500 rad. In addition, irradiation of intracellular DCFH and aqueous 2'-7'-dichlorofluorescein diacetate (DCFH-DA) resulted in DCF production, which suggested that oxidative molecules produced by aqueous radiolysis were detected by this assay. This study indicates that radiation doses of 1500 to 2500 rad, which are sufficient to prevent induction of graft-versus-host disease by transfused blood components, are not deleterious to neutrophil oxidative metabolism

  5. Human neutrophil elastase: mediator and therapeutic target in atherosclerosis.

    Science.gov (United States)

    Henriksen, Peter A; Sallenave, Jean-Michel

    2008-01-01

    Human neutrophil elastase (HNE) is present within atherosclerotic plaques where it contributes to matrix degradation and weakening of the vessel wall associated with the complications of aneurysm formation and plaque rupture. It is joined by other extracellular proteases in these actions but the broad range of substrates and potency of HNE coupled with the potential for rapid increases in HNE activity associated with neutrophil degranulation in acute coronary syndromes single this disruptive protease out as therapeutic target in atherosclerotic disease. This review summarises the role of HNE in neutrophil-mediated endothelial injury and the evidence for HNE as a mediator of atherosclerotic plaque development. The therapeutic potential of HNE neutralising antiproteases, alpha-1-antitrypsin and elafin, in atherosclerosis, is discussed. PMID:18289916

  6. Doxycycline induced photodamage to human neutrophils and tryptophan

    International Nuclear Information System (INIS)

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 μM doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D2O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D2O and nearly abolished in the presence of 0.25 mM NaN3, indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions. (author)

  7. Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy

    Science.gov (United States)

    Chu, Dafeng; Zhao, Qi; Yu, Jian; Zhang, Faya; Zhang, Hui; Wang, Zhenjia

    2016-01-01

    Cancer immunotherapy using tumor specific monoclonal antibodies (mAbs) presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma, initiates neutrophil recruitment in tumor responsible for cancer therapy. Here we report a strategy for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, we showed that systemically delivered albumin NPs increased in tumor when TA99 antibody was injected; and the nanoparticle tumor accumulation was mediated by neutrophils. After the administration of pyropheophorbide-a (Ppa) loaded albumin NPs and TA99, photodynamic therapy significantly suppressed the tumor growth and increased mouse survival compared with treatment with the NPs or TA99. The study reveals a new avenue to treat cancer by nanoparticle hitchhiking of immune systems to enhance delivery of therapeutics into tumor sites. PMID:26989887

  8. Doxycycline induced photodamage to human neutrophils and tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Sandberg, S.; Glette, J.; Hopen, G.; Solberg, C.O. (Haukeland Sykehus, Bergen (Norway))

    1984-01-01

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 ..mu..M doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D/sub 2/O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D/sub 2/O and nearly abolished in the presence of 0.25 mM NaN/sub 3/, indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions.

  9. Sagan numbers

    OpenAIRE

    Mendonça, J. Ricardo G.

    2012-01-01

    We define a new class of numbers based on the first occurrence of certain patterns of zeros and ones in the expansion of irracional numbers in a given basis and call them Sagan numbers, since they were first mentioned, in a special case, by the North-american astronomer Carl E. Sagan in his science-fiction novel "Contact." Sagan numbers hold connections with a wealth of mathematical ideas. We describe some properties of the newly defined numbers and indicate directions for further amusement.

  10. Fibonacci numbers

    CERN Document Server

    Vorob'ev, Nikolai Nikolaevich

    2011-01-01

    Fibonacci numbers date back to an 800-year-old problem concerning the number of offspring born in a single year to a pair of rabbits. This book offers the solution and explores the occurrence of Fibonacci numbers in number theory, continued fractions, and geometry. A discussion of the ""golden section"" rectangle, in which the lengths of the sides can be expressed as a ration of two successive Fibonacci numbers, draws upon attempts by ancient and medieval thinkers to base aesthetic and philosophical principles on the beauty of these figures. Recreational readers as well as students and teacher

  11. Spontaneous neutrophil activation in HTLV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Jaqueline B. Guerreiro

    2005-12-01

    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.

  12. Number names and number understanding

    DEFF Research Database (Denmark)

    Ejersbo, Lisser Rye; Misfeldt, Morten

    2014-01-01

    through using mathematical names for the numbers such as one-ten-one for 11 and five-ten-six for 56. The project combines the renaming of numbers with supporting the teaching with the new number names. Our hypothesis is that Danish children have more difficulties learning and working with numbers, because...... the Danish number names are more complicated than in other languages. Keywords: A research project in grade 0 and 1th in a Danish school, Base-10 system, two-digit number names, semiotic, cognitive perspectives....

  13. A case of refractory chronic neutrophilic pustular folliculitis treated with adalimumab

    DEFF Research Database (Denmark)

    Sand, Freja Laerke; Thomsen, Simon Francis

    2014-01-01

    Neutrophilic folliculitis is an often overlooked chronic condition characterized by a monomorphic eruption of "sterile" papulopustules. Neutrophilic folliculitis is often refractory to conventional treatment with topical and systemic antibiotics or isotretinoin. We report a case of severe pustula...

  14. Neutrophilic iron oxidizers adapted to highly oxic environments

    DEFF Research Database (Denmark)

    Gülay, Arda; Musovic, Sanin; Albrechtsen, Hans-Jørgen;

    carbon) while oxygen (O2) is the electron acceptor provided during the aeration process. Numerous previous studies have described neutrophilic iron oxidizers as a bacterial guild with a special niche preference, especially the transition zone between aerobic and anoxic regions, where abiotic chemical...... indicate that neutrophilic iron oxidizers in highly oxic environments like drinking water treatment systems can be abundant (5 E+04 to 7 E+05 cells per gram of wet sand material). It was furthermore observed that the diversity of the cultivated dominant iron oxidizers differs substantially from those...

  15. Generalized neutrophilic dermatosis: A rare presentation of myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Khodadad Kian

    2005-01-01

    Full Text Available We present a 30-year-old man admitted with generalized cutaneous lesions, fever and cough. Examination of skin biopsies of a papular lesion revealed dense neutrophilic infiltration of the upper dermis, so these lesions were diagnosed as neutrophilic dermatosis. Peripheral blood examination and bone marrow findings confirmed the diagnosis of myelodysplastic syndrome with excess blasts. The cutaneous lesions improved after administration of corticosteroid and follow-up bone marrow examination revealed a normocellular marrow. One year later he referred with acute myelogenous leukemia (AML-M0. Unfortunately, he did not respond to treatment and died a few months later due to disease progression.

  16. Local Rheology of Human Neutrophils Investigated Using Atomic Force Microscopy

    Directory of Open Access Journals (Sweden)

    Yong J. Lee, Dipika Patel, Soyeun Park

    2011-01-01

    Full Text Available During the immune response, neutrophils display localized mechanical events by interacting with their environment through the micro-vascular transit, trans-endothelial, and trans-epithelial migration. Nano-mechanical studies of human neutrophils on localized nano-domains could provide the essential information for understanding their immune responsive functions. Using the Atomic Force Microscopy (AFM - based micro-rheology, we have investigated rheological properties of the adherent human neutrophils on local nano-domains. We have applied the modified Hertz model to obtain the viscoelastic moduli from the relatively thick body regions of the neutrophils. In addition, by using more advanced models to account for the substrate effects, we have successfully characterized the rheological properties of the thin leading and tail regions as well. We found a regional difference in the mechanical compliances of the adherent neutrophils. The central regions of neutrophils were significantly stiffer (1,548 ± 871 Pa than the regions closer to the leading edge (686 ± 801 Pa, while the leading edge and the tail (494 ± 537 Pa regions were mechanically indistinguishable. The frequency-dependent elastic and viscous moduli also display a similar regional difference. Over the studied frequency range (100 to 300 Hz, the complex viscoelastic moduli display the partial rubber plateau behavior where the elastic moduli are greater than the viscous moduli for a given frequency. The non-disparaging viscous modulus indicates that the neutrophils display a viscoelastic dynamic behavior rather than a perfect elastic behavior like polymer gels. In addition, we found no regional difference in the structural damping coefficient between the leading edge and the cell body. Thus, we conclude that despite the lower loss and storage moduli, the leading edges of the human neutrophils display partially elastic properties similar to the cell body. These results suggest that the

  17. Human neutrophil elastase inhibitors in innate and adaptive immunity.

    Science.gov (United States)

    Fitch, P M; Roghanian, A; Howie, S E M; Sallenave, J-M

    2006-04-01

    Recent evidence shows that human neutrophil elastase inhibitors can be synthesized locally at mucosal sites. In addition to efficiently targeting bacterial and host enzymes, they can be released in the interstitium and in the lumen of mucosa, where they have been shown to have antimicrobial activities, and to activate innate immune responses. This review will address more particularly the pleiotropic functions of low-molecular-mass neutrophil elastase inhibitors [SLPI (secretory leucocyte proteinase inhibitor) and elafin] and, more specifically, their role in the development of the adaptive immune response. PMID:16545094

  18. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

    Directory of Open Access Journals (Sweden)

    Alexander D Malkin

    2015-10-01

    Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

  19. Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

    Directory of Open Access Journals (Sweden)

    Maria Galluzzo

    2015-01-01

    Full Text Available Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF. Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. βENaC overexpressing mice (βENaC-Tg were backcrossed with PI3Kγ-deficient (PI3KγKO mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF. Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240 on inflammatory cell number in BALF. Results. Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI3KγKO/βENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.

  20. Neutrophil DNA contributes to the antielastase barrier during acute lung inflammation.

    Science.gov (United States)

    Balloy, Viviane; Sallenave, Jean-Michel; Crestani, Bruno; Dehoux, Monique; Chignard, Michel

    2003-06-01

    During acute lung inflammation, the airspaces are invaded by circulating neutrophils. These may then injure tissues through the release of elastase. Different natural specific inhibitors such as alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin are nonetheless able to counteract the enzymatic activity of elastase. The present study was undertaken to assess the role of these different inhibitors in the intrinsic antielastase barrier during lipopolysaccharide-induced lung inflammation in mice. Upon intranasal administration of lipopolysaccharide to mice, the antielastase activity recovered from bronchoalveolar lavage fluids (BALF) increases progressively up to 48 h (7-fold) and returns to the basal level within 72 h. By contrast, when the same experiments are performed with neutropenic mice (pretreatment with an antigranulocyte antibody, or vinblastine), the increase is almost totally absent. Ultrafiltration of BALF through 100 kD cutoff membranes shows that the activity remains in the retentate, thus ruling out a role for native alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin. Gel filtration and fraction analysis show that the material eluted with a Mr of 600 kD. Agarose gel electrophoresis and ethidium bromide staining reveal that the activity corresponds to the presence a large amount of DNA. Interestingly, DNase treatment of the active fraction suppresses the antielastase activity. Analysis of BALF from patients with acute lung inflammation shows the presence of DNA with antielastase activity. We therefore concluded that during acute lung inflammation, the recruitment of neutrophils in the airspaces accounts for the increased presence of DNA, which in turn contributes to the antielastase barrier. PMID:12600833

  1. Mechanisms of neutrophil accumulation in the lungs of patients with idiopathic pulmonary fibrosis.

    OpenAIRE

    Hunninghake, G W; Gadek, J E; Lawley, T J; Crystal, R G

    1981-01-01

    Neutrophils are a characteristic feature of the alveolitis of idiopathic pulmonary fibrosis (IPF). a chronic disorder limited to lung. One mechanism by which neutrophils may be selectively attracted to lung and not other tissues is via the secretion of the neutrophil-specific chemotactic factor by alveolar macrophages. To evaluate the role of alveolar macrophages in modulating the migration of neutrophils to he lung in IPF, alveolar macrophages, obtained by bronchoalveolar lavage of patients ...

  2. Mannheimia haemolytica and Its Leukotoxin Cause Neutrophil Extracellular Trap Formation by Bovine Neutrophils▿

    OpenAIRE

    Aulik, Nicole A.; Hellenbrand, Katrina M.; Klos, Heather; Czuprynski, Charles J.

    2010-01-01

    Mannheimia haemolytica is an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of M. haemolytica causes NET formation by bovine neutrophils in a CD18-...

  3. Effect of Legionella pneumophila cytotoxic protease on human neutrophil and monocyte function

    DEFF Research Database (Denmark)

    Rechnitzer, C; Kharazmi, A

    1992-01-01

    protease on the chemotactic activity of neutrophils was demonstrated by the continued inhibition of neutrophil chemotaxis when the protease was removed following pre-incubation of the cells. In contrast, the enzyme had no effect on monocyte chemotaxis. The protease inhibited, also in a concentration...... activity of L. pneumophila protease on neutrophil chemotaxis and on the listericidal activity of human neutrophils and monocytes demonstrated in this study provides evidence for a role of this enzyme in the pathogenesis of Legionnaires' disease....

  4. Evidence for a self-enforcing inflammation in neutrophil-mediated chronic diseases

    OpenAIRE

    Overbeek, S.A.

    2011-01-01

    In summary, this thesis provides evidence for the self-sustaining role of neutrophils in the inflammatory state in the pathogenesis of COPD and CD. In active disease, neutrophils release proteolytic enzymes that breakdown collagen. One of the collagen fragments can be neutrophilic chemoattractant N-ac-PGP, which leads to enhanced neutrophil inflammation and further inflammation. In COPD, cigarette smoking initiates a vicious circle of events leading to collagen breakdown, PGP generation and P...

  5. Mouse neutrophils express functional umami taste receptor T1R1/T1R3

    OpenAIRE

    Lee, NaHye; Jung, Young Su; Lee, Ha Young; Kang, NaNa; Park, Yoo Jung; Hwang, Jae Sam; Bahk, Young Yil; Koo, JaeHyung; Bae, Yoe-Sik

    2014-01-01

    Neutrophils play an important role in the initiation of innate immunity against infection and injury. Although many different types of G-protein coupled receptors are functionally expressed in neutrophils, no reports have demonstrated functional expression of umami taste receptor in these cells. We observed that mouse neutrophils express the umami taste receptor T1R1/T1R3 through RNA sequencing and quantitative RT-PCR analysis. Stimulation of mouse neutrophils with L-alanine or L-serine, whic...

  6. Experimental study of natural circulation circuit

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, Wanderley F.; Su, Jian, E-mail: wlemos@lasme.coppe.ufrj.br, E-mail: sujian@lasme.coppe.ufrj.br [Coordenacao dos Programas de Pos-Graduacao de Engenharia (LASME/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Lab. de Simulacao e Metodos Numericos; Faccini, Jose L.H., E-mail: faccini@ien.gov.br [Instituto de Engenharia Nuclear (LTE/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab. de Termo-Hidraulica Experimental

    2011-07-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  7. Fort St. Vrain circulator operating experience

    International Nuclear Information System (INIS)

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs

  8. Eulerian numbers

    CERN Document Server

    Petersen, T Kyle

    2015-01-01

    This text presents the Eulerian numbers in the context of modern enumerative, algebraic, and geometric combinatorics. The book first studies Eulerian numbers from a purely combinatorial point of view, then embarks on a tour of how these numbers arise in the study of hyperplane arrangements, polytopes, and simplicial complexes. Some topics include a thorough discussion of gamma-nonnegativity and real-rootedness for Eulerian polynomials, as well as the weak order and the shard intersection order of the symmetric group. The book also includes a parallel story of Catalan combinatorics, wherein the Eulerian numbers are replaced with Narayana numbers. Again there is a progression from combinatorics to geometry, including discussion of the associahedron and the lattice of noncrossing partitions. The final chapters discuss how both the Eulerian and Narayana numbers have analogues in any finite Coxeter group, with many of the same enumerative and geometric properties. There are four supplemental chapters throughout, ...

  9. Index Numbers

    OpenAIRE

    Diewert, Erwin

    2007-01-01

    Index numbers are used to aggregate detailed information on prices and quantities into scalar measures of price and quantity levels or their growth. The paper reviews four main approaches to bilateral index number theory where two price and quantity vectors are to be aggregated: fixed basket and average of fixed baskets, stochastic, test or axiomatic and economic approaches. The paper also considers multilateral index number theory where it is necessary to construct price and quantity aggrega...

  10. File list: ALL.Bld.20.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Neutrophils hg19 All antigens Blood Neutrophils SRX956551,SRX95654...8,SRX956545,SRX956544,SRX956547,SRX956550,SRX956546,SRX956549,SRX956552 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.20.AllAg.Neutrophils.bed ...

  11. File list: ALL.Bld.05.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Neutrophils mm9 All antigens Blood Neutrophils SRX760584,SRX760581...,SRX760583,SRX760582,SRX760580,SRX801903 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Neutrophils.bed ...

  12. NEUTROPHIL DEPLETION ATTENUATES INTERLEUKIN-8 PRODUCTION IN MILD-OVERSTRETCHED VENTILATED NORMAL RABBIT LUNG

    Science.gov (United States)

    OBJECTIVE: Acute lung injury induced by lung overstretch is associated with neutrophil influx, but the pathogenic role of neutrophils in overstretch-induced lung injury remains unclear. DESIGN: To assess the contribution of neutrophils, we compared the effects of noninjurious lar...

  13. Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects

    NARCIS (Netherlands)

    Gazendam, R.P.; Hamme, J.L. van; Tool, A.T.; Houdt, M. van; Verkuijlen, P.J.; Herbst, M.; Liese, J.G.; Veerdonk, F.L. van de; Roos, D.; Berg, T.K. van den; Kuijpers, T.W.

    2014-01-01

    Invasive fungal infections, accompanied by high rates of mortality, represent an increasing problem in medicine. Neutrophils are the major effector immune cells in fungal killing. Based on studies with neutrophils from patients with defined genetic defects, we provide evidence that human neutrophils

  14. The dynamics of neutrophils in zebrafish (Danio rerio) during infection with the parasite Ichthyophthirius multifiliis

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff

    2016-01-01

    was infected with I. multifiliis and the neutrophil influx in the caudal fin was quantified. Twenty-four hours post infection (pi) the neutrophil count had gone up with an average of 3.4 fold. Forty-eight h pi the neutrophil count had dropped 12% and 72 h pi it had dropped to 21% compared to 24 h pi. At 72 h...

  15. Number names and number understanding

    DEFF Research Database (Denmark)

    Ejersbo, Lisser Rye; Misfeldt, Morten

    2014-01-01

    This paper concerns the results from the first year of a three-year research project involving the relationship between Danish number names and their corresponding digits in the canonical base 10 system. The project aims to develop a system to help the students’ understanding of the base 10 system...... through using mathematical names for the numbers such as one-ten-one for 11 and five-ten-six for 56. The project combines the renaming of numbers with supporting the teaching with the new number names. Our hypothesis is that Danish children have more difficulties learning and working with numbers, because...... the Danish number names are more complicated than in other languages. Keywords: A research project in grade 0 and 1th in a Danish school, Base-10 system, two-digit number names, semiotic, cognitive perspectives....

  16. Circulation of Stars

    Science.gov (United States)

    Boitani, P.

    2016-01-01

    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  17. Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide

    Directory of Open Access Journals (Sweden)

    Viktoriya I. Milanova

    2014-12-01

    Full Text Available Neutrophils play a crucial role in the pathogenesis of joint inflammatory diseases such as rheumatoid arthritis (RA. Therefore their elimination and/or a functional inhibition might have beneficial or even therapeutic effects in these diseases. In the present study we exploited the cytotoxic action of etoposide to deplete neutrophils. We administrated the drug twice (at day -3 and day -1 to SCID mice having intact innate immunity and a fail in T- and B-cell maturation. Ankle inflammation was induced by the injection of zymosan (ZY. Joint damage was evaluated by histology grading system for cell infiltration and proteoglycan loss and degree of cartilage erosion. The frequencies of mature Ly6G+CD11b+ cells in bone marrow (BM were monitored at days -4, -2 and 0 by flow cytometry. At day 7 of ankle inflammation the amounts of pro-inflammatory cytokines tumor necrosis factor (TNF-α and interleukin (IL-17 were measured by enzyme-linked immunosorbent assay (ELISA. Histological analysis of the joint sections showed decreased scores for cell infiltration and cartilage proteoglycan loss and reduced cartilage erosion in drug-treated zymosan injected mice in comparison to untreated group with ankle inflammation. Etoposide diminished cell numbers in BM, inhibits granulopoiesis triggered by zymosan and decreased the frequencies of mature Ly6G+CD11b+ cells in BM and eliminated Ly6G+ cells from blood and synovial fluid. We observed reduced TNF-α and impaired IL-17 production in etoposide-treated ZY group. Our data provide a proof-of principle that the elimination of neutrophils might be exploited in a design of new therapeutic approaches for joint inflammatory diseases.

  18. Protein-tyrosine phosphatase activity of Coxiella burnetii that inhibits human neutrophils

    International Nuclear Information System (INIS)

    Supernatants prepared from disrupted Coxiella burnetii posses acid phosphatase (ACP) activity that apparently accounts for the inhibition of the metabolic burst of formyl-Met-Leu-Phe(fMLP)-stimulated human neutrophils. Results are presented regarding purification and biochemical-biological characterization of the ACP. The highly purified enzyme, which exhibited an apparent M of 91 K and optimal activity at pH 5.0, also inhibited neutrophils. The enzyme retained full activity at pH 4.5, 5.5, and 7.4, when incubated overnight at 0 grad C and room temperature; at pH 5.5, it retained full activity after overnight incubation at 37 grad C. Apparently, the enzyme contains asparagine-linked but not serine- or threonine-liked glycan residues since its treatment with N-glycosidase F decreased its Mr to 87 K and no changes were detected with O-glycosidase. The enzyme's capacity to hydrolyze phosphate from a number of phosphate-containing compounds was examined; five phospho-compounds were significantly hydrolyzed: 5'-CMP > fructose 1,6-diphosphate > tyrosine phosphate > 3'-AMP >5'-AMP. The ACP also dephosphorylated 32P-Raytide, a phosphotyrosine-containing peptide. Dephosphorylation of Raytide was inhibited by the following phosphatase inhibitors: sodium molybdate, potassium fluoride, sodium ortho-vanadate and D2, a heteropolymolybdate compound. These results indicate that C.burnetii ACP may play a role in disrupting tyrosine phosphorylation/dephosphorylation reactions associated with the signal transduction pathway culminating in the metabolic burst. Interestingly, Western blot analysis of ACP-inhibited neutrophils showed a marked increase in tyrosine phosphorylation of a 44 K protein as compared to uninhibited cells. (author)

  19. Meridional circulation in turbulent protoplanetary disks

    OpenAIRE

    Fromang, Sebastien; Lyra, Wladimir; Masset, Frederic

    2011-01-01

    Based on the viscous disk theory, a number of recent studies have suggested there is large scale meridional circulation in protoplanetary disks. Such a flow could account for the presence of crystalline silicates, including calcium- and aluminum-rich inclusions (CAIs), at large distances from the sun. This paper aims at examining whether such large-scale flows exist in turbulent protoplanetary disks. High-resolution global hydrodynamical and magnetohydrodynamical (MHD) numerical simulations o...

  20. Early production of human neutrophils and platelets posttransplant is severely compromised by growth factor exposure.

    Science.gov (United States)

    Miller, Paul H; Knapp, David J H F; Beer, Philip A; MacAldaz, Margarita; Rabu, Gabrielle; Cheung, Alice M S; Wei, Lisa; Eaves, Connie J

    2016-07-01

    The critical human cells that produce neutrophils and platelets within 3 weeks in recipients of hematopoietic transplants are thought to produce these mature blood cells with the same kinetics in sublethally irradiated immunodeficient mice. Quantification of their numbers indicates their relative underrepresentation in cord blood (CB), likely explaining the clinical inadequacy of single CB units in rescuing hematopoiesis in myelosuppressed adult patients. We here describe that exposure of CD34(+) CB cells ex vivo to growth factors that markedly expand their numbers and colony-forming cell content also rapidly (within 24 hours) produce a significant and sustained net loss of their original short-term repopulating activity. This loss of short-term in vivo repopulating activity affects early platelet production faster than early neutrophil output, consistent with their origin from distinct input populations. Moreover, this growth factor-mediated loss is not abrogated by published strategies to increase progenitor homing despite evidence that the effect on rapid neutrophil production is paralleled in time and amount by a loss of the homing of their committed clonogenic precursors to the bone marrow. These results highlight the inability of in vitro or phenotype assessments to reliably predict clinical engraftment kinetics of cultured CB cells. PMID:27090409

  1. Generation of functional neutrophils from a mouse model of X-linked chronic granulomatous disorder using induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Sayandip Mukherjee

    Full Text Available Murine models of human genetic disorders provide a valuable tool for investigating the scope for application of induced pluripotent stem cells (iPSC. Here we present a proof-of-concept study to demonstrate generation of iPSC from a mouse model of X-linked chronic granulomatous disease (X-CGD, and their successful differentiation into haematopoietic progenitors of the myeloid lineage. We further demonstrate that additive gene transfer using lentiviral vectors encoding gp91(phox is capable of restoring NADPH-oxidase activity in mature neutrophils derived from X-CGD iPSC. In the longer term, correction of iPSC from human patients with CGD has therapeutic potential not only through generation of transplantable haematopoietic stem cells, but also through production of large numbers of autologous functional neutrophils.

  2. [Neutrophil disorders: diagnosis and hematopoietic stem cell transplantation].

    Science.gov (United States)

    Kobayashi, Masao

    2015-10-01

    Neutrophil disorders are classified into abnormal neutrophil function and granulopoiesis. The identification of genetic defects causing neutropenia and neutrophil dysfunction has revealed the mechanisms controlling myeloid differentiation and their functions. The International Union of Immunological Societies of Primary Immunodeficiencies represents the most current catalog of approximately 30 neutrophil disorders. In this report, we show the progress made in studies of the pathophysiology and treatment of these disorders, focusing on chronic granulomatous disease (CGD) and severe congenital neutropenia (SCN). Hematopoietic stem cell transplantation (HSCT) is the only available curative therapy for CGD and SCN. However, the use of HSCT as treatment for both diseases is limited by transplant-related mortality (TRM) because of active infections and intractable inflammatory complications. Recently, reduced-intensity conditioning regimens have been introduced to minimize the TRM and the late adverse effects of HSCT for both diseases. The results of HSCT using the RIC regimen for 40 patients with CGD and SCN in Hiroshima University Hospital are summarized herein. Determining the optimal line of treatment will require further accumulation to cases to refine HSCT for both diseases. PMID:26458464

  3. Anti-neutrophil cytoplasmic antibodies in idiopathic inflammatory disorders

    NARCIS (Netherlands)

    Mulder, Alide Heleen Leontine

    1994-01-01

    This thesis studies the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in idiopathic inflammatory disorders in which GS-ANA were described during the 60s: rheumatoid arthritis, autoimmune liver diseases, inflammatory bowel disease, and juvenile chronic arthritis. In all of these disorde

  4. Activity of neutrophil elastase reflects the progression of acute pancreatitis

    DEFF Research Database (Denmark)

    Novovic, Srdan; Andersen, Anders M; Nord, Magnus;

    2013-01-01

    Abstract Objective. Neutrophil elastase (NE) concentration is associated with progression of acute pancreatitis (AP), but measuring total NE concentration includes biologically inactive NE. This study aims to investigate the relationship between NE activity and the aetiology and severity of AP and...... was associated with predicted severity of AP and AP-associated respiratory failure. Specific NE inhibitors may have therapeutic potential in acute pancreatitis....

  5. Physiological concentrations of leptin do not affect human neutrophils.

    NARCIS (Netherlands)

    Kamp, V.M.; Langereis, J.D.; Aalst, C.W. van; Linden, J. van der; Ulfman, L.H.; Koenderman, L.

    2013-01-01

    Leptin is an adipokine that is thought to be important in many inflammatory diseases, and is known to influence the function of several leukocyte types. However, no clear consensus is present regarding the responsiveness of neutrophils for this adipokine. In this study a 2D DIGE proteomics approach

  6. Capillary plexuses are vulnerable to neutrophil extracellular traps.

    Science.gov (United States)

    Boneschansker, Leo; Inoue, Yoshitaka; Oklu, Rahmi; Irimia, Daniel

    2016-02-01

    Capillary plexuses are commonly regarded as reliable networks for blood flow and robust oxygen delivery to hypoxia sensitive tissues. They have high levels of redundancy to assure adequate blood supply when one or more of the capillaries in the network are blocked by a clot. However, despite having extensive capillary plexuses, many vital organs are often subject to secondary organ injury in patients with severe inflammation. Recent studies have suggested that neutrophils play a role in this pathology, even though their precise contribution remains elusive. Here we investigate the effect of chromatin fibres released from overly-activated neutrophils (neutrophil extracellular traps, NETs) on the flow of blood through microfluidic networks of channels replicating geometrical features of capillary plexuses. In an in vitro setting, we show that NETs can decouple the traffic of red blood cells from that of plasma in microfluidic networks. The effect is astonishingly disproportionate, with NETs from less than 200 neutrophils resulting in more than half of a 0.6 mm(2) microfluidic network to become void of red blood cell traffic. Importantly, the NETs are able to perturb the blood flow in capillary networks despite the presence of anti-coagulants. If verified to occur in vivo, this finding could represent a novel mechanism for tissue hypoxia and secondary organ injury during severe inflammation in patients already receiving antithrombotic and anticoagulant therapies. PMID:26797289

  7. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These...

  8. On the pharmacology of oxidative burst of neutrophils

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Harmatha, Juraj; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.

    2011-01-01

    Roč. 4, č. 2 (2011), A51-A51. ISSN 1337-6853. [TOXCON 2011. Interdisciplinary Toxicology Conference /16./. 17.05.2011-20.05.2011, Praha] Institutional research plan: CEZ:AV0Z40550506 Keywords : N-feruloyl-serotonin * oxidative burst * inhibition of neutrophil activation Subject RIV: CC - Organic Chemistry

  9. Flavonoids inhibit the respiratory burst of neutrophils in mammals

    Czech Academy of Sciences Publication Activity Database

    Číž, Milan; Denev, P.; Kratchanova, M.; Vašíček, Ondřej; Ambrožová, Gabriela; Lojek, Antonín

    2012-01-01

    Roč. 2012, č. 2012 (2012), ID 181295. ISSN 1942-0900 R&D Projects: GA ČR(CZ) GA524/08/1753 Institutional research plan: CEZ:AV0Z50040702 Keywords : flavonoids * neutrophils * respiratory burst Subject RIV: BO - Biophysics Impact factor: 3.393, year: 2012

  10. Modulation of neutrophil oxidative burst via histamine receptors

    Czech Academy of Sciences Publication Activity Database

    Číž, Milan; Lojek, Antonín

    2013-01-01

    Roč. 170, č. 1 (2013), s. 17-22. ISSN 0007-1188 R&D Projects: GA MŠk(CZ) LD11010 Institutional support: RVO:68081707 Keywords : neutrophil * oxidative burst * reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 4.990, year: 2013

  11. Polyphenol derivatives inhibit human neutrophil activity by suppressing oxidative burst

    Czech Academy of Sciences Publication Activity Database

    Drábiková, K.; Perečko, T.; Nosáľ, R.; Harmatha, Juraj; Šmidrkal, J.; Jančinová, V.

    2012-01-01

    Roč. 5, Suppl.1 (2012), s. 31-31. ISSN 1337-6853. [Interdisciplinary Toxicological Conference & Advanced Toxicological Course /17./. 27.08.2012-31.08.2012, Stará Lesná] Institutional research plan: CEZ:AV0Z40550506 Keywords : polyphenol derivatives * neutrophil activity * pinosylvin Subject RIV: CC - Organic Chemistry

  12. Clinical Observation of Ginsenosides in Treating Neutrophil Granulocytopenia

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@In order to explore the role of ginsenosides (GS) in treating neutrophil granulocytopenia (NGP), from January 1996 to December 1999 our hospital used GS in treating 53 patients of idiopathic NGP, which were compared with 52 patients treated by leucogen as control. Here it is reported as follows.

  13. On the pharmacology of oxidative burst of human neutrophils.

    Science.gov (United States)

    Nosáľ, R; Drábiková, K; Jančinová, V; Mačičková, T; Pečivová, J; Perečko, T; Harmatha, J; Šmidrkal, J

    2015-01-01

    The effect of three therapeutically used drugs and five polyphenolic compounds on the mechanism of oxidative burst was compared in whole blood and isolated neutrophils at cellular and molecular level. In 10 microM concentration, the compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin (N-f-5HT) > curcumin (CUR) > quercetin (QUER) > arbutin (ARB) > resveratrol (RES) > dithiaden (DIT) > carvedilol (CARV) > brompheniramine (BPA). The ratio between the percentage inhibition of extracellular versus intracellular chemiluminescence (CL) followed the rank order QUER > N-f-5HT > RES > CUR > DIT and is indicative of the positive effect of the compounds tested against oxidative burst of neutrophils, demonstrating suppression of reactive oxygen species extracellularly with minimal alteration of intracellular reactive oxygen species (ROS). Activation of protein kinase C was significantly decreased by DIT, CUR, QUER and N-f-5HT. CARV, DIT, QUER and ARB reduced activated neutrophil myeloperoxidase release more significantly compared with the effect on superoxide anion generation. All compounds tested increased the activity of caspase-3 in cell-free system. It is suggested that other regulatory mechanisms than protein kinase C might participate in the inhibition of neutrophil activation with the compounds tested. Different mechanisms are concerned in controlling the assembly of NADPH oxidase and the regulatory role of calcium ions is suggested. Compounds decreasing the amount of extracellular ROS generation, yet affecting but minimally intracellular ROS generation, are promising for further investigation in vivo. PMID:26681073

  14. Olfactomedin 4 defines a subset of human neutrophils

    DEFF Research Database (Denmark)

    Clemmensen, Stine N; Bohr, Christina T; Rørvig, Sara; Glenthøj, Andreas; Mora-Jensen, Helena; Cramer, Elisabeth P; Jacobsen, Lars C; Larsen, Maria T; Cowland, Jack B; Tanassi, Julia T; Heegaard, Niels H H; Wren, Jonathan D; Silahtaroglu, Asli N; Borregaard, Niels

    2012-01-01

    OLFM4 was identified initially as a gene highly induced in myeloid stem cells by G-CSF treatment. A bioinformatics method using a global meta-analysis of microarray data predicted that OLFM4 would be associated with specific granules in human neutrophils. Subcellular fractionation of peripheral...

  15. Phagocytic ability of neutrophils and monocytes in neonates

    Directory of Open Access Journals (Sweden)

    Mantagos Stephanos

    2011-04-01

    Full Text Available Abstract Background Infections by a variety of pathogens are a significant cause of morbidity and mortality during perinatal period. The susceptibility of neonates to bacterial infections has been attributed to immaturity of innate immunity. It is considered that one of the impaired mechanisms is the phagocytic function of neutrophils and monocytes. The purpose of the present study was to investigate the phagocytic ability of neonates at birth. Methods The phagocytic ability of neutrophils and monocytes of 42 neonates was determined using the Phagotest flow cytometry method, that assesses the intake of E. Coli by phagocytes, in cord blood and in peripheral blood 3 days after birth. Fifteen healthy adults were included in the study as controls. Results The phagocytic ability of neutrophils in the cord blood of neonates was significantly reduced compared to adults. The 3rd postnatal day the reduction of phagocytic ability of neutrophils was no longer significant compared to adults. The phagocytic ability of monocytes did not show any difference from that of adults either at birth or the 3rd postnatal day. Conclusions Our findings indicate that the intake of E. Coli by phagocytes is impaired at birth in both preterm and full term neonates compared to adults. This defect is transient, with the phagocytic ability in neonates reaching that of the adults 3 days after birth.

  16. On the Pharmacology of Oxidative Burst of Human Neutrophils

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.; Harmatha, Juraj; Šmidrkal, J.

    2015-01-01

    Roč. 64, Suppl 4 (2015), S445-S452. ISSN 0862-8408 Institutional support: RVO:61388963 Keywords : human neutrophils * oxidative burst * chemiluminescence * protein kinase C * apoptosis Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.293, year: 2014 http://www.biomed.cas.cz/physiolres/pdf/64/64_S445.pdf

  17. In vivo involvement of polymorphonuclear neutrophils in Leishmania infantum infection

    Directory of Open Access Journals (Sweden)

    Le Fichoux Yves

    2001-08-01

    Full Text Available Abstract Background The role of lymphocytes in the specific defence against L. infantum has been well established, but the part played by polynuclear neutrophil (PN cells in controlling visceral leishmaniasis was much less studied. In this report we examine in vivo the participation of PN in early and late phases of infection by L. infantum. Results Promastigote phagocytosis and killing occurs very early after infection, as demonstrated by electron microscopy analyses which show in BALB/c mouse spleen, but not in liver, numerous PN harbouring ultrastructurally degraded parasites. It is shown, using mAb RB6-8C5 directed against mature mouse granulocytes, that in chronically infected mice, long-term PN depletion did not enhance parasite counts neither in liver nor in spleen, indicating that these cells are not involved in the late phase of L. infantum infection. In acute stage of infection, in mouse liver, where L. infantum load is initially larger than that in spleen but resolves spontaneously, there was no significant effect of neutrophils depletion. By contrast, early in infection the neutrophil cells crucially contributed to parasite killing in spleen, since PN depletion, performed before and up to 7 days after the parasite inoculation, resulted in a ten-fold increase of parasite burden. Conclusions Taken together these data show that neutrophil cells contribute to the early control of the parasite growth in spleen but not in liver and that these cells have no significant effect late in infection in either of these target organs.

  18. Hepatocyte growth factor is produced by blood and alveolar neutrophils in acute respiratory failure.

    Science.gov (United States)

    Jaffré, Sandrine; Dehoux, Monique; Paugam, Catherine; Grenier, Alain; Chollet-Martin, Sylvie; Stern, Jean-Baptiste; Mantz, Jean; Aubier, Michel; Crestani, Bruno

    2002-02-01

    We tested the novel hypothesis that neutrophils in the lung or the airspaces may produce hepatocyte growth factor (HGF) in ventilated patients with acute respiratory failure. Neutrophils were purified from blood and bronchoalveolar lavage (BAL) fluid samples from 16 mechanically ventilated patients who underwent BAL for a diagnostic workup of ventilator-acquired pneumonia. Most of the patients had pneumonia (n = 11). Ten nonventilated patients served as controls. Both blood and BAL neutrophils released HGF in vitro. Basal HGF secretion by blood neutrophils from controls was 823 (666) pg x ml(-1) x 10(-7) neutrophils (median, 25th-75th percentile) and doubled to 1,730 (1,684-2,316) pg x ml(-1) x 10(-7) neutrophils (P = 0.001) with lipopolysaccharide (LPS) stimulation. Basal HGF secretion by blood neutrophils from patients was similar [956 (655-2,140) pg x ml(-1) x 10(-7) neutrophils, P = 0.4] and doubled with LPS stimulation [2,767 (2,165-3,688) pg x ml(-1) x 10(-7) neutrophils, P < 0.0001 vs. controls]. Alveolar neutrophils released HGF in vitro [653 (397-1,209) pg x ml(-1) x 10(-7) neutrophils]. LPS stimulation did not significantly increase the HGF release from alveolar neutrophils [762 (434-1,305) pg x ml(-1) x 10(-7) neutrophils]. BAL HGF positively correlated with the BAL neutrophil count (P = 0.01, R = 0.58). We conclude that blood and alveolar neutrophils from patients with acute respiratory failure can produce HGF, a mitogenic factor that may enhance the alveolar repair process. PMID:11792636

  19. Antimicrobial peptides and nitric oxide production by neutrophils from periodontitis subjects

    Directory of Open Access Journals (Sweden)

    F.S. Mariano

    2012-11-01

    Full Text Available Neutrophils play an important role in periodontitis by producing nitric oxide (NO and antimicrobial peptides, molecules with microbicidal activity via oxygen-dependent and -independent mechanisms, respectively. It is unknown whether variation in the production of antimicrobial peptides such as LL-37, human neutrophil peptides (HNP 1-3, and NO by neutrophils influences the pathogenesis of periodontal diseases. We compared the production of these peptides and NO by lipopolysaccharide (LPS-stimulated neutrophils isolated from healthy subjects and from patients with periodontitis. Peripheral blood neutrophils were cultured with or without Aggregatibacter actinomycetemcomitans-LPS (Aa-LPS, Porphyromonas gingivalis-LPS (Pg-LPS and Escherichia coli-LPS (Ec-LPS. qRT-PCR was used to determine quantities of HNP 1-3 and LL-37 mRNA in neutrophils. Amounts of HNP 1-3 and LL-37 proteins in the cell culture supernatants were also determined by ELISA. In addition, NO levels in neutrophil culture supernatants were quantitated by the Griess reaction. Neutrophils from periodontitis patients cultured with Aa-LPS, Pg-LPS and Ec-LPS expressed higher HNP 1-3 mRNA than neutrophils from healthy subjects. LL-37 mRNA expression was higher in neutrophils from patients stimulated with Aa-LPS. Neutrophils from periodontitis patients produced significantly higher LL-37 protein levels than neutrophils from healthy subjects when stimulated with Pg-LPS and Ec-LPS, but no difference was observed in HNP 1-3 production. Neutrophils from periodontitis patients cultured or not with Pg-LPS and Ec-LPS produced significantly lower NO levels than neutrophils from healthy subjects. The significant differences in the production of LL-37 and NO between neutrophils from healthy and periodontitis subjects indicate that production of these molecules might influence individual susceptibility to important periodontal pathogens.

  20. General circulation of the Jovian stratosphere

    Science.gov (United States)

    Medvedev, Alexander S.; Sethunadh, Jisesh; Hartogh, Paul

    The stratosphere of Jupiter is a convectively stable and coldest layer that extends for about 350 km above the tropopause. The dynamics of stratospheres of fast rotating gas giants differ from that of terrestrial-like planets, their modeling is more challenging, and is still little known despite a growing number of observations. We present results of simulations with a newly developed Jovian general circulation model, which covers the altitudes between one bar and one microbar. The results demonstrate a high sensitivity of the circulation to variations of eddy diffusion, which, in turn, depends on the model resolution and assumed background viscosity. In the lower stratosphere, the multiple circulation cells associated with the tropospheric alternating jets dominate. Higher, a weak two-cell equator-to-pole transport forms due to the influence of smaller-scale eddies. The strength and extent of this circulation are defined by the momentum supplied by shallow and vertically propagating waves, and are consistent with observations of the Shoemaker-Levi 9 comet traces. We will also discuss the dynamical implications of our recent finding that radiative forcing exponentially increases with height, rather than approximately constant throughout the Jovian stratosphere, as was thought before (see presentation of T. Kuroda at B0.3 session).

  1. Chocolate Numbers

    OpenAIRE

    Ji, Caleb; Khovanova, Tanya; Park, Robin; Song, Angela

    2015-01-01

    In this paper, we consider a game played on a rectangular $m \\times n$ gridded chocolate bar. Each move, a player breaks the bar along a grid line. Each move after that consists of taking any piece of chocolate and breaking it again along existing grid lines, until just $mn$ individual squares remain. This paper enumerates the number of ways to break an $m \\times n$ bar, which we call chocolate numbers, and introduces four new sequences related to these numbers. Using various techniques, we p...

  2. Number theory

    CERN Document Server

    Andrews, George E

    1994-01-01

    Although mathematics majors are usually conversant with number theory by the time they have completed a course in abstract algebra, other undergraduates, especially those in education and the liberal arts, often need a more basic introduction to the topic.In this book the author solves the problem of maintaining the interest of students at both levels by offering a combinatorial approach to elementary number theory. In studying number theory from such a perspective, mathematics majors are spared repetition and provided with new insights, while other students benefit from the consequent simpl

  3. Magic Numbers

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    THE last digit of my home phone number in Beijing is 4. “So what?” European readers might ask.This was my attitude when I first lived in China; I couldn't understand why Chinese friends were so shocked at my indifference to the number 4. But China brings new discoveries every day, and I have since seen the light. I know now that Chinese people have their own ways of preserving their well being, and that they see avoiding the number 4 as a good way to stay safe.

  4. Colchicine modulates expression of pro-inflammatory genes in neutrophils from patients with familial Mediterranean fever and healthy subjects.

    Science.gov (United States)

    Manukyan, G; Petrek, M; Tomankova, T; Martirosyan, A; Tatyan, M; Navratilova, Z; Paulu, D; Kriegova, E

    2013-01-01

    Colchicine (Col) is a microtubule depolymerizing drug, widely used for treatment of familial Mediterranean fever (FMF). Mechanisms by which Col exerts its beneficial effects are not yet completely understood, especially with respect to gene expression in polymorphonuclear neutrophils (PMNs), the main effector cells in acute inflammatory attacks of FMF. This study was, therefore, designed to elucidate possible modulatory effect of Col on expression of inflammation-related genes in circulating PMNs from 16 FMF patients in the remission period and 11 healthy subjects. In vitro effect of Col exposure (1 microg/ml) on expression of 8 selected genes was examined using quantitative real-time RT-PCR. Col up-regulated expression of IL-8 and IL-1beta genes in FMF (13-fold and 2.7-fold, p less than 0.05, respectively) and healthy (3-fold and 6.5-fold, p less than 0.05, respectively) PMNs, and down-regulated caspase-1 in FMF neutrophils (3-fold, p less than 0.05). In FMF PMNs treated with Col mRNAs of IL-8 (51-fold, p less than 0.01) and c-FOS (7-fold, p less than 0.05) transcripts were elevated compared to those from healthy subjects. By contrast, caspase-1 mRNA was decreased in FMF neutrophils compared to healthy cells (1.6-fold, p less than 0.05). Hereby, we provide evidence that, at least in vitro, Col displays pro-inflammatory potential in respect to IL-1beta and IL-8 genes. At the same time, our findings implicate suppression of caspase-1 expression by Col as a potential mechanism for its effects in FMF treatment. PMID:23830384

  5. Protrusive and Contractile Forces of Spreading Human Neutrophils.

    Science.gov (United States)

    Henry, Steven J; Chen, Christopher S; Crocker, John C; Hammer, Daniel A

    2015-08-18

    Human neutrophils are mediators of innate immunity and undergo dramatic shape changes at all stages of their functional life cycle. In this work, we quantified the forces associated with a neutrophil's morphological transition from a nonadherent, quiescent sphere to its adherent and spread state. We did this by tracking, with high spatial and temporal resolution, the cell's mechanical behavior during spreading on microfabricated post-array detectors printed with the extracellular matrix protein fibronectin. Two dominant mechanical regimes were observed: transient protrusion and steady-state contraction. During spreading, a wave of protrusive force (75 ± 8 pN/post) propagates radially outward from the cell center at a speed of 206 ± 28 nm/s. Once completed, the cells enter a sustained contractile state. Although post engagement during contraction was continuously varying, posts within the core of the contact zone were less contractile (-20 ± 10 pN/post) than those residing at the geometric perimeter (-106 ± 10 pN/post). The magnitude of the protrusive force was found to be unchanged in response to cytoskeletal inhibitors of lamellipodium formation and myosin II-mediated contractility. However, cytochalasin B, known to reduce cortical tension in neutrophils, slowed spreading velocity (61 ± 37 nm/s) without significantly reducing protrusive force. Relaxation of the actin cortical shell was a prerequisite for spreading on post arrays as demonstrated by stiffening in response to jasplakinolide and the abrogation of spreading. ROCK and myosin II inhibition reduced long-term contractility. Function blocking antibody studies revealed haptokinetic spreading was induced by β2 integrin ligation. Neutrophils were found to moderately invaginate the post arrays to a depth of ∼1 μm as measured from spinning disk confocal microscopy. Our work suggests a competition of adhesion energy, cortical tension, and the relaxation of cortical tension is at play at the onset of

  6. Effects of MCI-186 upon neutrophil-derived active oxygens.

    Science.gov (United States)

    Sumitomo, K; Shishido, N; Aizawa, H; Hasebe, N; Kikuchi, K; Nakamura, M

    2007-01-01

    Reactions of 3-methyl-1-phenyl-2-pyrazoline-5-one (MCI-186) with hypochlorous acid and superoxide were analysed by spectrophotometry and mass spectrometry. The results were applied to the neutrophil system to evaluate the scavenging activity of neutrophil-derived active oxygen species by MCI-186. MCI-186 reacted rapidly with hypochlorous acid (1 x 10(6) M(-1)s(-1)) to form a chlorinated intermediate, followed by a slow conversion to a new spectrum. MCI-186 consumed 3 moles of hypochlorous acid and did not react with superoxide. The newly synthesized fluorescence probes, 2-[6-(4'-amino)-phenoxy-3H-xanthen-3-on-9-yl]benzoic acid (APF) and 2-[6-(4'-hydroxy)phenoxy-3H-anthen-3-on-9-yl]benzoic acid (HPF) successfully detected neutrophil-derived active oxygens (Setsukinai K, Urano Y, Kakinuma K, Majima HJ, Nagano T. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem 2003; 278: 3170-3175). The rate constants for the reaction of hypochlorous acid with MCI-186 and fluorescence probes was in the order of MCI-186 > APF > HPF. Fluorescence due to the oxidation of APF and HPF was observed with the stimulated neutrophils. The result that the intensity from APF oxidation was higher than that from HPF oxidation is compatible with reports that APF selectively reacts with hypochlorous acid. Fluorescence due to oxidation of both APF and HPF decreased when the reactions were carried out in the presence of a fluorescence probe and MCI-186 in a dose-dependent manner. These results indicate that MCI-186 effectively scavenges neutrophil-derived hypochlorous acid and other active oxygens. PMID:17705989

  7. Ocean General Circulation Models

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jin-Ho; Ma, Po-Lun

    2012-09-30

    1. Definition of Subject The purpose of this text is to provide an introduction to aspects of oceanic general circulation models (OGCMs), an important component of Climate System or Earth System Model (ESM). The role of the ocean in ESMs is described in Chapter XX (EDITOR: PLEASE FIND THE COUPLED CLIMATE or EARTH SYSTEM MODELING CHAPTERS). The emerging need for understanding the Earth’s climate system and especially projecting its future evolution has encouraged scientists to explore the dynamical, physical, and biogeochemical processes in the ocean. Understanding the role of these processes in the climate system is an interesting and challenging scientific subject. For example, a research question how much extra heat or CO2 generated by anthropogenic activities can be stored in the deep ocean is not only scientifically interesting but also important in projecting future climate of the earth. Thus, OGCMs have been developed and applied to investigate the various oceanic processes and their role in the climate system.

  8. Interleukin 17A controls Interleukin 17F production and maintains blood neutrophil counts in mice

    OpenAIRE

    von Vietinghoff, Sibylle; Ley, Klaus

    2009-01-01

    Granulocyte colony-stimulating factor (G-CSF), its receptor and interleukin-17 receptor A (IL-17RA) are all required to maintain baseline neutrophil counts in mice. Here, we tested whether IL-17F could compensate and maintain baseline neutrophil counts in the absence of IL-17A. Unlike the reduced neutrophil counts found in IL-17RA deficient mice, neutrophil counts were mildly increased in IL-17A deficient (Il17a-/-) animals. There was no evidence for infection or altered neutrophil function. ...

  9. Polymorphonuclear neutrophils in periodontitis and their possible modulation as a therapeutic approach.

    Science.gov (United States)

    Nicu, Elena A; Loos, Bruno G

    2016-06-01

    The main focus of this review is polymorphonuclear neutrophilic granulocytes. Polymorphonuclear neutrophils play a pivotal role in normal host resistance to subgingival dental-plaque biofilm. Both hyper- and hypo-responsiveness of the immune system toward the microbial challenge in periodontitis have been described. We review polymorphonuclear neutrophil physiology with emphasis on the role of neutrophil functions and dysfunctions in periodontitis. Text boxes are given at the end of each subsection, which present the current knowledge on neutrophil-modulating agents as a potential therapeutic approach in periodontitis. PMID:27045435

  10. Trypanosoma cruzi: circulating antigens

    Directory of Open Access Journals (Sweden)

    V. Bongertz

    1981-03-01

    Full Text Available Circulating antigens were detected in sera of mice experimentally infected with a high close of Trypanosoma cruzi by reaction with sera from chronically infected mice. The immunodiffusion reaction between homologous acute and chronic sera produced four precipitation lines. By reaction with chronic mouse serum, circulating antingens were detected in sera from heavily infected hamsters, dogs, rabbits and in sera from chagasic patients. A reaction was also found in urine from acutely infected mice and dogs. Trypanosoma cruzi exoantigen was detected in trypanosome culture medium and in the supernatant of infected cell cultures. Attempts to isolate the antigens are described.Antígenos circulantes foram detectados em soros de camundongos infectados experimentalmente com elevadas doses de Trypanosoma cruzi pela reação com soros obtidos de camundongos em fase crônica de infecção. A reação de imunodifusão entre soros homólogos agudo e crônico produziu quatro linhas de precipitação. Por reação com soro crônico de camundongo antígenos circulantes foram detectados em soros de crícetos, cães e coelhos infectados com doses elevadas de Trypanosoma cruzi e em soros de pacientes chagásicos. Uma reação foi também observada com urina de camundongos e cães infectados de forma aguda. Exoantígeno de Trypanosoma cruzi foi detectado em meio de cultura de tripanosomas e em sobrenadantes de culturas de células infectadas. Tentativas de isolamento dos antigenos são descritas.

  11. Frequencies of human neutrophil antigen-4 and human neutrophil antigen-5 among Thai blood donors

    Directory of Open Access Journals (Sweden)

    Onruedee Khantisitthiporn

    2015-01-01

    Full Text Available Context: Antibodies against human neutrophil antigens (HNAs are implicated in immune-mediated neutropenia, transfusion-related acute lung injury and febrile transfusion reactions. Aims: This study aimed to determine HNA gene frequencies of the HNA-4 and HNA-5 systems among Thai populations and compare these frequencies with those previously reported for other populations. Materials and Methods: 800 DNA samples obtained from 500 unrelated healthy blood donors from Bangkok and 300 samples from Chiang Mai, Thailand were included. Samples were typed for each HNA allele including HNA-4a, HNA-4b, HNA-5a, and HNA-5b using an in-house polymerase chain reaction with sequence-specific primer technique. Results: The frequencies of HNA-4a and HNA-4b alleles in central Thais were 0.975 and 0.025, respectively and for Northern Thais, their frequencies were 0.965 and 0.035, respectively. For HNA-5a and HNA-5b alleles, their frequencies were 0.771 and 0.229; 0.748, and 0.252 in central and Northern Thais, respectively. The frequencies of HNA-4 and HNA-5 systems in central Thais are closely related to those in Northern Thais (P > 0.05. However, their frequencies were different from other populations (P 0.05. Conclusion: This study could contribute to predict the risk of alloimmunization to HNA-4 and HNA-5 systems, especially in feto-maternal incompatibility in Thais.

  12. Influence of Vitamin C Supplementation on Oxidative Stress and Neutrophil Inflammatory Response in Acute and Regular Exercise

    Directory of Open Access Journals (Sweden)

    Ljiljana M. Popovic

    2015-01-01

    Full Text Available Exercise induces a multitude of physiological and biochemical changes in blood affecting its redox status. Tissue damage resulting from exercise induces activation of inflammatory cells followed by the increased activity of myeloperoxidase (MPO in circulation. Vitamin C readily scavenges free radicals and may thereby prevent oxidative damage of important biological macromolecules. The aim of this study was to examine the effect of vitamin C supplementation on oxidative stress and neutrophil inflammatory response induced by acute and regular exercise. Experiment was conducted on acute exercise group (performing Bruce Treadmill Protocol (BTP and regular training group. Markers of lipid peroxidation, malondialdehyde (MDA, MPO activity, and vitamin C status were estimated at rest and after BTP (acute exercise group and before and after vitamin C supplementation in both groups. Our results showed increased postexercise Asc in serum independently of vitamin supplementation. They also showed that vitamin C can significantly decrease postexercise MDA level in both experimental groups. Increased postexercise MPO activity has been found in both groups and was not affected by vitamin C supplementation. We concluded that vitamin C supplementation can suppress lipid peroxidation process during exercise but cannot affect neutrophil inflammatory response in either exercise group.

  13. Central role of neutrophil in the pathogenesis of severe acute pancreatitis.

    Science.gov (United States)

    Yang, Zhi-Wen; Meng, Xiao-Xiao; Xu, Ping

    2015-11-01

    Severe acute pancreatitis (SAP) is an acute abdominal disease with the strong systemic inflammatory response, and rapidly progresses from a local pancreatic damage into multiple organ dysfunction. For many decades, the contributions of neutrophils to the pathology of SAP were traditionally thought to be the chemokine and cytokine cascades that accompany inflammation. In this review, we focus mainly on those recently recognized aspects of neutrophils in SAP processes. First, emerging evidence suggests that therapeutic interventions targeting neutrophils significantly lower tissue damage and protect against the occurrence of pancreatitis. Second, trypsin activation promotes the initial neutrophils recruitment into local pancreas, and subsequently neutrophils infiltration in turn triggers trypsin production. Finally, neutrophils have the unique ability to release neutrophil extracellular traps even in the absence of pathogens. PMID:26249268

  14. TROPICAL METEOROLOGY & Climate: Hadley Circulation

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jian; Vecchi, Gabriel A.

    2015-01-30

    The Hadley circulation, a prominent circulation feature characterized by rising air near the Equator and sinking air in the subtropics, defines the position of dry subtropical areas and is a fundamental regulator of the earth’s energy and momentum budgets. The character of the Hadley circulation, and its related precipitation regimes, exhibits variation and change in response to both climate variability and radiative forcing changes. The strength and position of the Hadley circulation change from year to year paced by El Niño and La Niña events. Over the last few decades of the twentieth century, the Hadley cell has expanded poleward in both hemispheres, with changes in atmospheric composition (including stratospheric ozone depletion and greenhouse gas increases) thought to have contributed to its expansion. This article introduces the basic phenomenology and driving mechanism of the Hadley circulation and discusses its variations under both natural and anthropogenic climate forcings.

  15. Sino-Danish Brain Circulation

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe

    2014-01-01

    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  16. Number Guessing

    Science.gov (United States)

    Sezin, Fatin

    2009-01-01

    It is instructive and interesting to find hidden numbers by using different positional numeration systems. Most of the present guessing techniques use the binary system expressed as less-than, greater-than or present-absent type information. This article describes how, by employing four cards having integers 1-64 written in different colours, one…

  17. Meridional circulation in turbulent protoplanetary disks

    CERN Document Server

    Fromang, Sebastien; Masset, Frederic

    2011-01-01

    Based on viscous disk theory, a number of recent studies have suggested the existence of a large scale meridional circulation in protoplanetary disks. Such a flow could account for the presence of crystalline silicates, among which Calcium and Aluminium-rich Inclusions (CAIs), at large distances from the sun. This paper aims at examining whether such large scale flows exist in turbulent protoplanetary disks. High resolution global hydrodynamical and magnetohydrodynamical numerical simulations of turbulent protoplanetary disks are used to infer the properties of the flow in such disks. By performing hydrodynamic simulations using explicit viscosity, we demonstrate that our numerical setup does not suffer from any numerical artifact. The aforementioned meridional circulation is readily recovered in viscous and laminar disks. In MHD simulations, the magneto-rotational instability drives turbulence in the disks. Averaging out the turbulent fluctuations over long timescale, the results fail to show any large scale...

  18. Peritumoural neutrophils negatively regulate adaptive immunity via the PD-L1/PD-1 signalling pathway in hepatocellular carcinoma

    OpenAIRE

    He, GaiXia; Zhang, Henghui; Zhou, JinXue; Wang, Beibei; Chen, Yanhui; Kong, Yaxian; Xie, Xingwang; Wang, Xueyan; Fei, Ran; Wei, Lai; Chen, Hongsong; ZENG, HUI

    2015-01-01

    Background PD-L1 expression on neutrophils contributes to the impaired immune response in infectious disease, but the detailed role of PD-L1 expression on neutrophils in HCC remains unclear. Methods We investigated the phenotype and morphology of neutrophils infiltrated in tumour tissues from both patients with HCC and hepatoma-bearing mice. Results We found that neutrophils dominantly infiltrated in the peritumoural region. The neutrophil-to-T cell ratio (NLR) was higher in peritumoural tiss...

  19. Neutrophil gelatinase-associated lipocalin (NGAL)

    OpenAIRE

    Lange, Jessica

    2011-01-01

    Patients with an end stage renal disease (ERDS) are addicted to renal replacement therapy. Alternatively there is the option for kidney transplantation but the donor pool for kidney transplantation worldwide has plateaued in recent years. Expansion of the donor pool by inclusion of donors who previously would not have been accepted for kidney transplantation and living related donations are actually the only options to increase the number of kidney transplantation. However, data on donor-...

  20. Number Theories

    CERN Document Server

    St-Amant, Patrick

    2010-01-01

    We will see that key concepts of number theory can be defined for arbitrary operations. We give a generalized distributivity for hyperoperations (usual arithmetic operations and operations going beyond exponentiation) and a generalization of the fundamental theorem of arithmetic for hyperoperations. We also give a generalized definition of the prime numbers that are associated to an arbitrary n-ary operation and take a few steps toward the development of its modulo arithmetic by investigating a generalized form of Fermat's little theorem. Those constructions give an interesting way to interpret diophantine equations and we will see that the uniqueness of factorization under an arbitrary operation can be linked with the Riemann zeta function. This language of generalized primes and composites can be used to restate and extend certain problems such as the Goldbach conjecture.

  1. Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia

    Directory of Open Access Journals (Sweden)

    G. Camus

    1998-01-01

    Full Text Available To address the question of whether translocation of bacterial lipopolysaccharide (LPS into the blood could be involved in the process of exercise-induced polymorphonuclear neutrophil (PMN activation, 12 healthy male subjects who took part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road race were studied. While there was no detectable amount of endotoxin in the blood samples drawn at rest, exercise was followed by the appearance of circulating endotoxin molecules at the end of competition in four subjects, and after one and 24 h recovery in three and seven athletes, respectively. The concentrations of plasma granulocyte myeloperoxidase ([MPO], were significantly higher immediately after exercise and one hour later than baseline values (P<0.001. This variable returned to pre-race levels the day after exercise, despite the presence of detectable amounts of LPS, at that time, in seven athletes. The absence of significant correlation (r=0.26;P=0.383 and temporal association between [MPO]and plasma endotoxin levels led us to conclude that endotoxaemia was not involved in the process of exercise-induced PMN degranulation observed in our subjects.

  2. Activated neutrophils disrupt endothelial monolayer integrity by an oxygen radical-independent mechanism

    International Nuclear Information System (INIS)

    The effect of activated neutrophils on endothelial monolayer integrity in vitro has been measured by assessing the capacity of endothelial monolayers on polycarbonate filters to exclude 125I-albumin. Although formylmethionyl-leucyl-phenylalanine (FMLP)-activated neutrophils failed to induce 51Cr-release or detachment after 4 hours of incubation with endothelial monolayers cultured in polystyrene wells, FMLP-activated neutrophils produced a marked increase in the passage of 125I-albumin across bovine aortic or pulmonary artery endothelial monolayers on polycarbonate filters. This effect was evident as early as 30 minutes following the addition of FMLP-activated neutrophils to the monolayer and reached 180% over control values at 2 hours (p . 0.001). Light and transmission electron microscopic examination of the polycarbonate filters exposed to FMLP-activated neutrophils revealed focal disruption of the endothelial monolayers. Chronic granulomatous disease neutrophils produced similar disruption of the endothelial monolayer at 2 hours. Moreover, catalase and superoxide dismutase failed to reduce significantly the neutrophil-mediated increase in 125I-albumin passage at 2 hours. Cell-free postsecretory supernatants of FMLP-activated neutrophils, leukotriene C4, and platelet activating factor did not induce a significant increase in 125I-albumin passage across the endothelial monolayers. Of note, FMLP-activated neutrophils from a patient with a congenital abnormality of neutrophil adhesion and chemotaxis did not induce disruption of the monolayer or increase 125I-albumin passage

  3. The dynamics of neutrophils in zebrafish (Danio rerio) during infection with the parasite Ichthyophthirius multifiliis.

    Science.gov (United States)

    von Gersdorff Jørgensen, Louise

    2016-08-01

    Ichthyophthirius multifiliis is a ciliated protozoan parasite infecting the skin and gills of freshwater fish. Neutrophils are attracted to the infection sites, as a part of the innate immune response. In this study a transgenic line of zebrafish (Tg(MPO:GFP)(i114)) with GFP-tagged neutrophils was infected with I. multifiliis and the neutrophil influx in the caudal fin was quantified. Twenty-four hours post infection (pi) the neutrophil count had gone up with an average of 3.4 fold. Forty-eight h pi the neutrophil count had dropped 12% and 72 h pi it had dropped to 21% compared to 24 h pi. At 72 h pi the neutrophil count was 2.7 times higher than prior to infection. A few dead parasites were observed, which were disintegrated and covered internally and externally with neutrophils. Live parasites, both surrounded by neutrophils and with no neutrophils in the near vicinity, were found during the infection. Neutrophils interacted directly with the parasites with pseudopod formation projecting towards the pathogen. These results indicate a strong innate immune response immediately following infection and/or a subsequent immune evasion by the parasite. PMID:27231191

  4. Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

    Science.gov (United States)

    Xu, Yuanfu; Li, Hongmei; Bajrami, Besnik; Kwak, Hyunjeong; Cao, Shannan; Liu, Peng; Zhou, Jiaxi; Zhou, Yuan; Zhu, Haiyan; Ye, Keqiang; Luo, Hongbo R.

    2013-01-01

    Diphosphoinositol pentakisphosphate (InsP7), a higher inositol phosphate containing energetic pyrophosphate bonds, is beginning to emerge as a key cellular signaling molecule. However, the various physiological and pathological processes that involve InsP7 are not completely understood. Here we report that cigarette smoke (CS) extract and nicotine reduce InsP7 levels in aging neutrophils. This subsequently leads to suppression of Akt deactivation, a causal mediator of neutrophil spontaneous death, and delayed neutrophil death. The effect of CS extract and nicotine on neutrophil death can be suppressed by either directly inhibiting the PtdIns(3,4,5)P3/Akt pathway, or increasing InsP7 levels via overexpression of InsP6K1, an inositol hexakisphosphate (InsP6) kinase responsible for InsP7 production in neutrophils. Delayed neutrophil death contributes to the pathogenesis of CS-induced chronic obstructive pulmonary disease. Therefore, disruption of InsP6K1 augments CS-induced neutrophil accumulation and lung damage. Taken together, these results suggest that CS and nicotine delay neutrophil spontaneous death by suppressing InsP7 production and consequently blocking Akt deactivation in aging neutrophils. Modifying neutrophil death via this pathway provides a strategy and therapeutic target for the treatment of tobacco-induced chronic obstructive pulmonary disease. PMID:23610437

  5. Systemic hypoxia enhances exercise-mediated bactericidal and subsequent apoptotic responses in human neutrophils.

    Science.gov (United States)

    Wang, Jong-Shyan; Chiu, Ya-Ting

    2009-10-01

    Phagocytosis and oxidative burst are critical host defense mechanisms in which neutrophils clear invading pathogens. Clearing phagocytic neutrophils by triggering apoptosis is an essential process for controlling inflammation. This study elucidates how various exercise bouts with/without hypoxia affected neutrophil bactericidal activity and subsequent apoptosis in humans. Fifteen sedentary males performed six distinct experimental tests in an air-conditioned normobaric hypoxia chamber: two normoxic exercises [strenuous exercise (SE; up to maximal O2 consumption) and moderate exercise (ME; 50% maximal O2 consumption for 30 min) while exposed to 21% O2], two hypoxic exercises (ME for 30 min while exposed to 12% and 15% O2), and two hypoxic exposures (resting for 30 min while exposed to 12% and 15% O2). The results showed that 1) plasma complement-C3a desArg/C4a desArg/C5a concentrations were increased, 2) expressions of L-selectin/lymphocyte functin-associated antigen-1/Mac-1/C5aR on neutrophils were enhanced, 3) phagocytosis of neutrophils to Esherichia coli and release of neutrophil oxidant products by E. coli were elevated, and 4) E. coli-induced phosphotidylserine exposure or caspase-3 activation of neutrophils were promoted immediately and 2 h after both 12% O2 exposure at rest and with ME as well as normoxic SE. Although neither normoxic ME nor breathing 15% O2 at rest influenced these complement- and neutrophil-related immune responses, ME at both 12% and 15% O2 resulted in enhanced complement activation in the blood, expressions of opsonic/complement receptors on neutrophils, or the bactericidal activity and apoptosis of neutrophils. Moreover, the increased neutrophil oxidant production and apoptosis by normoxic SE and hypoxic ME were ameliorated by treating neutrophils with diphenylene iodonium (a NADPH oxidase inhibitor). Therefore, we conclude that ME at 12-15% O2 enhances bactericidal capacity and facilitates the subsequent apoptosis of neutrophils. PMID

  6. Neutrophil recruitment to the brain in mouse and human ischemic stroke.

    Science.gov (United States)

    Perez-de-Puig, Isabel; Miró-Mur, Francesc; Ferrer-Ferrer, Maura; Gelpi, Ellen; Pedragosa, Jordi; Justicia, Carles; Urra, Xabier; Chamorro, Angel; Planas, Anna M

    2015-02-01

    Neutrophils are rapidly recruited in response to local tissue infection or inflammation. Stroke triggers a strong inflammatory reaction but the relevance of neutrophils in the ischemic brain is not fully understood, particularly in the absence of reperfusion. We investigated brain neutrophil recruitment in two murine models of permanent ischemia induced by either cauterization of the distal portion of the middle cerebral artery (c-MCAo) or intraluminal MCA occlusion (il-MCAo), and three fatal cases of human ischemic stroke. Flow cytometry analyses revealed progressive neutrophil recruitment after c-MCAo, lesser neutrophil recruitment following il-MCAo, and absence of neutrophils after sham operation. Confocal microscopy identified neutrophils in the leptomeninges from 6 h after the occlusion, in the cortical basal lamina and cortical Virchow-Robin spaces from 15 h, and also in the cortical brain parenchyma at 24 h. Neutrophils showed signs of activation including histone-3 citrullination, chromatin decondensation, and extracellular projection of DNA and histones suggestive of extracellular trap formation. Perivascular neutrophils were identified within the entire cortical infarction following c-MCAo. After il-MCAo, neutrophils prevailed in the margins but not the center of the cortical infarct, and were intraluminal and less abundant in the striatum. The lack of collaterals to the striatum and a collapsed pial anastomotic network due to brain edema in large hemispheric infarctions could impair neutrophil trafficking in this model. Neutrophil extravasation at the leptomeninges was also detected in the human tissue. We concluded that neutrophils extravasate from the leptomeningeal vessels and can eventually reach the brain in experimental animal models and humans with prolonged arterial occlusion. PMID:25548073

  7. NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis.

    Science.gov (United States)

    Röhm, Marc; Grimm, Melissa J; D'Auria, Anthony C; Almyroudis, Nikolaos G; Segal, Brahm H; Urban, Constantin F

    2014-05-01

    NADPH oxidase is a crucial enzyme in antimicrobial host defense and in regulating inflammation. Chronic granulomatous disease (CGD) is an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates. Aspergillus species are ubiquitous, filamentous fungi, which can cause invasive aspergillosis, a major cause of morbidity and mortality in CGD, reflecting the critical role for NADPH oxidase in antifungal host defense. Activation of NADPH oxidase in neutrophils can be coupled to the release of proteins and chromatin that comingle in neutrophil extracellular traps (NETs), which can augment extracellular antimicrobial host defense. NETosis can be driven by NADPH oxidase-dependent and -independent pathways. We therefore undertook an analysis of whether NADPH oxidase was required for NETosis in Aspergillus fumigatus pneumonia. Oropharyngeal instillation of live Aspergillus hyphae induced neutrophilic pneumonitis in both wild-type and NADPH oxidase-deficient (p47(phox-/-)) mice which had resolved in wild-type mice by day 5 but progressed in p47(phox-/-) mice. NETs, identified by immunostaining, were observed in lungs of wild-type mice but were absent in p47(phox-/-) mice. Using bona fide NETs and nuclear chromatin decondensation as an early NETosis marker, we found that NETosis required a functional NADPH oxidase in vivo and ex vivo. In addition, NADPH oxidase increased the proportion of apoptotic neutrophils. Together, our results show that NADPH oxidase is required for pulmonary clearance of Aspergillus hyphae and generation of NETs in vivo. We speculate that dual modulation of NETosis and apoptosis by NADPH oxidase enhances antifungal host defense and promotes resolution of inflammation upon infection clearance. PMID:24549323

  8. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    OpenAIRE

    Nielsen, Ole H.; Bouchelouche, Pierre N.; Dag Berild

    1992-01-01

    Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l) was as potent as the calcium ionophore A23187 (10 μmol/l) for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the de...

  9. Interplay between shear stress and adhesion on neutrophil locomotion.

    Science.gov (United States)

    Smith, Lee A; Aranda-Espinoza, Helim; Haun, Jered B; Hammer, Daniel A

    2007-01-15

    Leukocyte locomotion over the lumen of inflamed endothelial cells is a critical step, following firm adhesion, in the inflammatory response. Once firmly adherent, the cell will spread and will either undergo diapedesis through individual vascular endothelial cells or will migrate to tight junctions before extravasating to the site of injury or infection. Little is known about the mechanisms of neutrophil spreading or locomotion, or how motility is affected by the physical environment. We performed a systematic study to investigate the effect of the type of adhesive ligand and shear stress on neutrophil motility by employing a parallel-plate flow chamber with reconstituted protein surfaces of E-selectin, E-selectin/PECAM-1, and E-selectin/ICAM-1. We find that the level and type of adhesive ligand and the shear rate are intertwined in affecting several metrics of migration, such as the migration velocity, random motility, index of migration, and the percentage of cells moving in the direction of flow. On surfaces with high levels of PECAM-1, there is a near doubling in random motility at a shear rate of 180 s(-1) compared to the motility in the absence of flow. On surfaces with ICAM-1, neutrophil random motility exhibits a weaker response to shear rate, decreasing slightly when shear rate is increased from static conditions to 180 s(-1), and is only slightly higher at 1000 s(-1) than in the absence of flow. The random motility increases with increasing surface concentrations of E-selectin and PECAM-1 under static and flow conditions. Our findings illustrate that the endothelium may regulate neutrophil migration in postcapillary venules through the presentation of various adhesion ligands at sites of inflammation. PMID:17071667

  10. Genetic Diversity as Consequence of a Microaerobic and Neutrophilic Lifestyle

    OpenAIRE

    Krüger, Nora-Johanna; Knüver, Marie-Theres; Zawilak-Pawlik, Anna; Appel, Bernd; Stingl, Kerstin

    2016-01-01

    As a neutrophilic bacterium, Helicobacter pylori is growth deficient under extreme acidic conditions. The gastric pathogen is equipped with an acid survival kit, regulating urease activity by a pH-gated urea channel, opening below pH 6.5. After overcoming acid stress, the bacterium’s multiplication site is situated at the gastric mucosa with near neutral pH. The pathogen exhibits exceptional genetic variability, mainly due to its capability of natural transformation, termed competence. Using ...

  11. Genetic Diversity as Consequence of a Microaerobic and Neutrophilic Lifestyle.

    OpenAIRE

    Nora-Johanna Krüger; Marie-Theres Knüver; Anna Zawilak-Pawlik; Bernd Appel; Kerstin Stingl

    2016-01-01

    As a neutrophilic bacterium, Helicobacter pylori is growth deficient under extreme acidic conditions. The gastric pathogen is equipped with an acid survival kit, regulating urease activity by a pH-gated urea channel, opening below pH 6.5. After overcoming acid stress, the bacterium's multiplication site is situated at the gastric mucosa with near neutral pH. The pathogen exhibits exceptional genetic variability, mainly due to its capability of natural transformation, termed competence. Using ...

  12. Neutrophil elastase-mediated increase in airway temperature during inflammation

    DEFF Research Database (Denmark)

    Schmidt, Annika; Belaaouaj, Azzaq; Bissinger, Rosi;

    2014-01-01

    Background How elevated temperature is generated during airway infections represents a hitherto unresolved physiological question. We hypothesized that innate immune defence mechanisms would increase luminal airway temperature during pulmonary infection. Methods We determined the temperature in t......, under anaerobic conditions at 38 °C vs 30 °C revealed increased virulence traits and characteristic cell wall changes. Conclusion Neutrophil elastase mediates increase in airway temperature, which may contribute to P. aeruginosa selection during the course of chronic infection in CF....

  13. Down-regulation of human neutrophil activity by natural polyphenols

    Czech Academy of Sciences Publication Activity Database

    Drábiková, K.; Perečko, T.; Nosáľ, R.; Harmatha, Juraj; Šmidrkal, J.; Jančinová, V.

    Bratislava : Institute of Experimental Pharmacology & Toxicology SAS, 2012 - (Bauer, V.; Mach, M.; Navarová, J.; Sotníková, R.), s. 98-108 ISBN 978-80-971042-0-7. [Drugs: Their Action in Pharmacology and Toxicology. Bratislava (SK), 31.05.2012] Institutional research plan: CEZ:AV0Z40550506 Keywords : activity of neutrophils * reactive oxygen species * natural polyphenols Subject RIV: CC - Organic Chemistry

  14. Membrane capacitance techniques to monitor granule exocytosis in neutrophils.

    OpenAIRE

    Lollike, K; Lindau, M

    1999-01-01

    Cell membranes behave like electrical capacitors and changes in cell capacitance therefore reflect changes in the cell area. Monitoring capacitance can thus be used to study dynamic cellular phenomenon involving rapid changes in cell surface, such as exo- and/or endocytosis. In this review focus is on the use of capacitance techniques to study exocytosis in human neutrophils. We compare the whole-cell and the cell-attached capacitance techniques, and we review the complete literature dealing ...

  15. Integrin-dependent Neutrophil Migration in the Injured Mouse Cornea

    OpenAIRE

    Hanlon, Samuel D.; Smith, C. Wayne; Sauter, Marika N; Burns, Alan R.

    2014-01-01

    As an early responder to an inflammatory stimulus, neutrophils (PMNs) must exit the vasculature and migrate through the extravascular tissue to the site of insult, which is often remote from the point of extravasation. Following a central epithelial corneal abrasion, PMNs recruited from the peripheral limbal vasculature migrate into the avascular corneal stroma. In vitro studies suggest PMN locomotion over 2-D surfaces is dependent on integrin binding while migration within 3-D matrices can b...

  16. Neutrophil mediated smooth muscle cell loss precedes allograft vasculopathy

    Directory of Open Access Journals (Sweden)

    Lee Timothy DG

    2010-06-01

    Full Text Available Abstract Background Cardiac allograft vasculopathy (AV is a pathological process of vascular remodeling leading to late graft loss following cardiac transplantation. While there is consensus that AV is alloimmune mediated, and evidence that the most important alloimmune target is medial smooth muscle cells (SMC, the role of the innate immune response in the initiation of this disease is still being elucidated. As ischemia reperfusion (IR injury plays a pivotal role in the initiation of AV, we hypothesize that IR enhances the early innate response to cardiac allografts. Methods Aortic transplants were performed between fully disparate mouse strains (C3H/HeJ and C57BL/6, in the presence of therapeutic levels of Cyclosporine A, as a model for cardiac AV. Neutrophils were depleted from some recipients using anti-PMN serum. Grafts were harvested at 1,2,3,5d and 1,2wk post-transplant. Ultrastructural integrity was examined by transmission electron microscopy. SMC and neutrophils were quantified from histological sections in a blinded manner. Results Grafts exposed to cold ischemia, but not transplanted, showed no medial SMC loss and normal ultrastructural integrity. In comparison, allografts harvested 1d post-transplant exhibited > 90% loss of SMC (p Conclusions These novel data show that there is extensive damage to medial SMC at 1d post-transplant. By depleting neutrophils from recipients it was demonstrated that a portion of the SMC loss was mediated by neutrophils. These results provide evidence that IR activation of early innate events contributes to the etiology of AV.

  17. Pharmacological inhibition of neutrophil pro-inflammatory activity

    Czech Academy of Sciences Publication Activity Database

    Jančinová, V.; Perečko, T.; Harmatha, Juraj; Nosáľ, R.; Drábiková, K.

    Bratislava : Institute of Experimental Pharmacology & Toxicology SAS, 2012 - (Bauer, V.; Mach, M.; Navarová, J.; Sotníková, R.), s. 66-75 ISBN 978-80-971042-0-7. [Drugs: Their Action in Pharmacology and Toxicology. Bratislava (SK), 31.05.2012] Institutional research plan: CEZ:AV0Z40550506 Keywords : neutrophil oxidative burst * apoptosis * polyphenols Subject RIV: CC - Organic Chemistry

  18. Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

    OpenAIRE

    Lee, W. L.; Shalita, A R; Suntharalingam, K; Fikrig, S M

    1982-01-01

    The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorph...

  19. High glucose impairs superoxide production from isolated blood neutrophils

    DEFF Research Database (Denmark)

    Perner, A; Nielsen, S E; Rask-Madsen, J

    2003-01-01

    Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This stud...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

  20. Phosphoproteins and the activation of the neutrophil respiratory burst oxidase

    International Nuclear Information System (INIS)

    The respiratory burst oxidase is a neutrophil enzyme that converts oxygen to O2-. It is dormant in resting cells but is activated when the cells are exposed to phorbol myristate acetate (PMA). PMA also induces the incorporation of 32P into certain neutrophil proteins. To determine whether phosphorylation of these proteins is related to oxidase activation, protein phosphorylation was studied in patients with chronic granulomatous disease (GCD), a group of inherited conditions in which oxidase activity is missing. In normals, neutrophil activation by PMA is associated with the phosphorylation inter alia of 48K proteins at pI 7.3 and 7.8. There is also inconstant phosphorylation of a 48K protein at pI 6.8. In 4 patients with X-linked chronic granulomatous disease (CGD), phosphorylation of pp48/6.8 and pp48/7.3 was absent, while in autosomal recessive CGD, phosphorylation of all 3 of these proteins was absent in 3 patients and significantly diminished in a fourth. These results suggest that the phosphorylation of these proteins is related to the activation of the respiratory burst oxidase. By peptide mapping, these 3 proteins appear to consist of a single peptide species whose pI variability may be due to post-translational modification. The only phosphoamino acid found in pp48/7.3 was phosphoserine

  1. Correlation of lactoferrin with neutrophilic inflammation in body fluids.

    Science.gov (United States)

    Martins, C A; Fonteles, M G; Barrett, L J; Guerrant, R L

    1995-11-01

    We have reported that lactoferrin, a 77-kDa iron-binding glycoprotein found in secondary neutrophil granules, provides a useful marker of fecal leukocytes in fecal specimens from patients with inflammatory diarrhea (R. L. Guerrant, V. Araujo, E. Soares, K. Kotloff, A. A. M. Lima, W. H. Cooper, and A. G. Lee, J. Clin. Microbiol. 30:1238-1242, 1992). In order to determine the usefulness of this marker of neutrophilic inflammation in different body fluids, we examined blood, gingival swabs, sputum, and saliva using antilactoferrin antibodies (lactoferrin latex agglutination [LFLA]). LFLA titers in whole blood samples were 8,000). While the overlap precludes a useful role in the identification of neutropenia, these data confirm that lactoferrin titers of > 1:100 indeed indicate inflammation in fluid specimens. On quantitative elution of lactoferrin from gingival swabs, all 7 patients with dental plaque had titers of 1:200 to 1:400; 9 of 12 patients with clinical gingivitis had LFLA titers of 1:200 to 1:1,600, while all 7 individuals with healthy gums and teeth and 4 edentulous patients had LFLA titers of or = 1:400 (7 were 1:1,600) while 11 normal saliva samples showed titers of < or = 1:100. Lactoferrin titers in sputum, gingival swabs, and whole blood correlate with the presence of neutrophils or inflammation in these specimens and may offer a convenient rapid test for inflammatory processes. PMID:8574844

  2. Flavonoids Inhibit the Respiratory Burst of Neutrophils in Mammals

    Directory of Open Access Journals (Sweden)

    Milan Ciz

    2012-01-01

    Full Text Available Neutrophils represent the front-line defence cells in protecting organisms against infection and play an irreplaceable role in the proper performance of the immune system. As early as within the first minutes of stimulation, neutrophilic NADPH oxidase is activated, and cells release large quantities of highly toxic reactive oxygen species (ROS. These oxidants can be highly toxic not only for infectious agents but also for neighboring host tissues. Since flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of ROS production. The present paper summarizes contemporary knowledge on the effects of various flavonoids on the respiratory burst of mammalian neutrophils. It can be summarized that the inhibitory effects of flavonoids on the respiratory burst of phagocytes are mediated via inhibition of enzymes involved in cell signaling as well as via modulation of redox status. However, the effects of flavonoids are even more complex, and several sites of action, depending upon the flavonoid structure and way of application, are included.

  3. Effect of glutamine supplementation on neutrophil function in male judoists.

    Science.gov (United States)

    Sasaki, Eiji; Umeda, Takashi; Takahashi, Ippei; Arata, Kojima; Yamamoto, Yousuke; Tanabe, Masaru; Oyamada, Kazuyuki; Hashizume, Erika; Nakaji, Shigeyuki

    2013-01-01

    Glutamine is an important amino acid for immune function. Though high intensity and prolonged exercise decreases plasma glutamine concentration and causes immune suppression, the relationship between neutrophil functions and glutamine has not yet been found. The purpose of this study was to investigate the impacts of glutamine supplementation on neutrophil function. Twenty-six male university judoists were recruited. Subjects were classified into glutamine and control groups. The glutamine group ingested 3000 mg of glutamine per day and the control group ingested placebo for 2 weeks. Examinations were performed at the start of preunified loading exercise (pre-ULE), then 1 and 2 weeks after ULE (post-ULE). Reactive oxygen species (ROS) production, phagocytic activity, serum opsonic activity and serum myogenic enzymes were measured. Differences between the levels obtained in pre-ULE and post-ULE for the two groups were compared. In the glutamine group, ROS production activity increased 1 week after ULE, whereas it was not observed in the control group (P glutamine group remained unchanged by supplementation during ULE. Glutamine supplementation has prevented excessive muscle damage and suppression of neutrophil function, especially in ROS production activity, even during an intensive training period. PMID:23348981

  4. Phosphoproteins and the activation of the neutrophil respiratory burst oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Okamura, N.; Curnutte, J.T.; Babior, B.M.

    1987-05-01

    The respiratory burst oxidase is a neutrophil enzyme that converts oxygen to O/sub 2//sup -/. It is dormant in resting cells but is activated when the cells are exposed to phorbol myristate acetate (PMA). PMA also induces the incorporation of /sup 32/P into certain neutrophil proteins. To determine whether phosphorylation of these proteins is related to oxidase activation, protein phosphorylation was studied in patients with chronic granulomatous disease (GCD), a group of inherited conditions in which oxidase activity is missing. In normals, neutrophil activation by PMA is associated with the phosphorylation inter alia of 48K proteins at pI 7.3 and 7.8. There is also inconstant phosphorylation of a 48K protein at pI 6.8. In 4 patients with X-linked chronic granulomatous disease (CGD), phosphorylation of pp48/6.8 and pp48/7.3 was absent, while in autosomal recessive CGD, phosphorylation of all 3 of these proteins was absent in 3 patients and significantly diminished in a fourth. These results suggest that the phosphorylation of these proteins is related to the activation of the respiratory burst oxidase. By peptide mapping, these 3 proteins appear to consist of a single peptide species whose pI variability may be due to post-translational modification. The only phosphoamino acid found in pp48/7.3 was phosphoserine.

  5. Osmotically induced cytosolic free Ca(2+) changes in human neutrophils.

    Science.gov (United States)

    Morris, M R; Doull, I J; Hallett, M B

    2001-02-01

    Cytosolic free Ca(2+) concentration in neutrophils was measured by ratiometric fluorometry of intracellular fura2. Increasing the extracellular osmolarity, by either NaCl (300-600 mM) or sucrose (600-1200 mM), caused a rise in cytosolic free Ca(2+) (Delta(max) approximately equal to 600 nM). This was not due to cell lysis as the cytosolic free Ca(2+) concentration was reversed by restoration of isotonicity and a second rise in cytosolic free Ca(2+) could be provoked by repeating the change in extracellular osmolarity. Furthermore, the rise in cytosolic free Ca(2+) concentration occurred in the absence of extracellular Ca(2+), demonstrating that release of intracellular fura2 into the external medium did not occur. The osmotically-induced rise in cytosolic free Ca(2+) was not inhibited by either the phospholipase C-inhibitor U73122, or the microfilament inhibitor cytochalasin B, suggesting that neither signalling via inositol tris-phosphate or the cytoskeletal system were involved. However, the rise in cytosolic free Ca(2+) may have resulted from a reduction in neutrophil water volume in hyperosmotic conditions. As these rises in cytosolic Ca(2+) (Delta(max) approximately equal to 600 nM) were large enough to provoke changes in neutrophil activity, we propose that conditions which removes cell water may similarly elevate cytosolic free Ca(2+) to physiologically important levels. PMID:11341979

  6. Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach

    Directory of Open Access Journals (Sweden)

    Ceballos Guillermo

    2009-06-01

    Full Text Available Abstract Background The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. Methods In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. Results Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5. Conclusion These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group. On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises.

  7. Comparative evaluation of the role of the adhesion molecule CD177 in neutrophil interactions with platelets and endothelium.

    Science.gov (United States)

    Pliyev, Boris K; Menshikov, Mikhail

    2012-09-01

    Neutrophil-specific glycoprotein CD177 is expressed on a subset of human neutrophils and has been shown to be a counter-receptor for platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31). Previous studies have demonstrated that the interaction of CD177 with endothelial PECAM-1 supports neutrophil transendothelial migration resulting in preferential transmigration of the CD177-expressing neutrophil subset. As PECAM-1 is also abundantly expressed on platelets, we addressed a follow-up suggestion that CD177/PECAM-1 adhesive interaction may mediate platelet-neutrophil interactions and CD177-positive neutrophils may have a competitive advantage over CD177-negative neutrophils in binding platelets. Here, we report that CD177-positive and CD177-negative neutrophils do not differ significantly in their capacity to form platelet-neutrophil conjugates as assayed in whole blood and in mixed preparations of isolated platelets and neutrophils. Under flow conditions, neither platelet nor neutrophil activation resulted in preferential binding of platelets to CD177-expressing neutrophils. Furthermore, no significant difference was found in the ability of both neutrophil subsets to adhere to and migrate across surface-adherent activated platelets, whereas predominantly CD177-positive neutrophils migrated across HUVEC monolayers. In addition, we demonstrated that S(536) N dimorphism of PECAM-1, which affects CD177/PECAM-1 interaction, did not influence the equal capacity of the two neutrophil subsets to interact with platelets but influenced significantly the transendothelial migration of CD177-expressing neutrophils. Thus, CD177/PECAM-1 adhesive interaction, while contributing to neutrophil-endothelial cell interaction in neutrophil transendothelial migration, does not contribute to or is redundant in platelet-neutrophil interactions. PMID:22690867

  8. Usefulness of a selective neutrophil elastase inhibitor, sivelestat, in acute lung injury patients with sepsis

    Directory of Open Access Journals (Sweden)

    Miyoshi S

    2013-04-01

    Full Text Available Seigo Miyoshi,1 Hironobu Hamada,1,2 Ryoji Ito,1 Hitoshi Katayama,1 Kazunori Irifune,1 Toshimitsu Suwaki,3 Norihiko Nakanishi,4 Takanori Kanematsu,5 Kentaro Dote,6 Mayuki Aibiki,7 Takafumi Okura,1 Jitsuo Higaki1 1Department of Integrated Medicine and Informatics, Ehime University, Graduate School of Medicine, Toon, 2Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 3Department of Respiratory Medicine, Sumitomo Besshi Hospital, Niihama, 4Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, 5Department of Respiratory Medicine, Matsuyama Red Cross Hospital, Matsuyama, 6Intensive Care Division, Ehime University Hospital, Toon, 7Department of Emergency Medicine, School of Medicine, Ehime University, Toon, Japan Background: Neutrophil elastase plays a crucial role in the development of acute lung injury (ALI in patients with systemic inflammatory response syndrome (SIRS. The clinical efficacy of the neutrophil elastase inhibitor, sivelestat, for patients with ALI associated with SIRS has not been convincingly demonstrated. The aim of this study was to determine if there are clinical features of patients with this condition that affect the efficacy of sivelestat. Methods: This was a retrospective study of 110 ALI patients with SIRS. Clinical information, including the etiology of ALI, the number of organs failing, scoring systems for assessing the severity of illness, and laboratory data, was collected at the time of diagnosis. Information on the number of ventilator-free days (VFDs and changes in PaO2/FIO2 (ΔP/F before and 7 days after the time of ALI diagnosis was also collected. The effect of sivelestat on ALI patients was also examined based on whether they had sepsis and whether their initial serum procalcitonin level was ≥0.5 ng/mL. Results: There were 70 patients who were treated with sivelestat and 40 control patients. VFDs and ΔP/F were significantly higher in the treated

  9. Cryptococcal Glucuronoxylomannan Inhibits Adhesion of Neutrophils to Stimulated Endothelium In Vitro by Affecting Both Neutrophils and Endothelial Cells

    OpenAIRE

    Ellerbroek, Pauline M.; Hoepelman, Andy I.M.; Wolbers, Floor; Zwaginga, Jaap Jan; Coenjaerts, Frank E. J.

    2002-01-01

    Cryptococcal infections are often characterized by a paucity of leukocytes in the infected tissues. Previous research has shown that the capsular polysaccharide glucuronoxylomannan (GXM) inhibits leukocyte migration. In this study we investigated whether the capsular polysaccharide GXM affects the migration of neutrophils (polymorphonuclear leukocytes [PMN]) through the endothelium by interfering with adhesion in a static adhesion model. Pretreatment of PMN with GXM inhibited PMN adhesion to ...

  10. Morphine reduces local cytokine expression and neutrophil infiltration after incision

    Directory of Open Access Journals (Sweden)

    Li Xiangqi

    2007-10-01

    Full Text Available Abstract Background Inflammation and nociceptive sensitization are hallmarks of tissue surrounding surgical incisions. Recent studies demonstrate that several cytokines may participate in the enhancement of nociception near these wounds. Since opioids like morphine interact with neutrophils and other immunocytes, it is possible that morphine exerts some of its antinociceptive action after surgical incision by altering the vigor of the inflammatory response. On the other hand, keratinocytes also express opioid receptors and have the capacity to produce cytokines after injury. Our studies were directed towards determining if opioids alter cytokine production near incisions and to identify cell populations responsible for producing these cytokines. Results A murine incisional model was used to measure the effects of acute morphine administration (0.1–10 mg/kg on nociceptive thresholds, neutrophil infiltration and cytokine production in hind paw skin 30 minutes and 2 hours after incision. Incised hind paws displayed profound allodynia which was reduced by morphine (0.1–10 mg/kg in the 2 hours following incision. Skin samples harvested from these mice showed enhanced levels of 5 cytokines: IL-1β, IL-6, tumor necrosis factor alpha (TNFα, granulocyte colony stimulating factor (G-CSF and keratinocyte-derived cytokine (KC. Morphine reduced these incision-stimulated levels. Separate analyses measuring myeloperoxidase (MPO and using immunohistochemistry demonstrated that morphine dose-dependently reduced the infiltration of neutrophils into the peri-incisional tissue. The dose of morphine required for reduction of cytokine accumulation, however, was below that required for inhibition of peri-incisional neutrophil infiltration. Additional immunohistochemical studies revealed wound edge keratinocytes as being an important source of cytokines in the acute phase after incision. Conclusion Acute morphine administration of doses as low as 0.1 mg/kg reduces

  11. Apoptosis of circulating lymphocytes during pediatric cardiac surgery

    Science.gov (United States)

    Bocsi, J.; Pipek, M.; Hambsch, J.; Schneider, P.; Tárnok, A.

    2006-02-01

    There is a constant need for clinical diagnostic systems that enable to predict disease course for preventative medicine. Apoptosis, programmed cell death, is the end point of the cell's response to different induction and leads to changes in the cell morphology that can be rapidly detected by optical systems. We tested whether apoptosis of T-cells in the peripheral blood is useful as predictor and compared different preparation and analytical techniques. Surgical trauma is associated with elevated apoptosis of circulating leukocytes. Increased apoptosis leads to partial removal of immune competent cells and could therefore in part be responsible for reduced immune defence. Cardiovascular surgery with but not without cardiopulmonary bypass (CPB) induces transient immunosuppression. Its effect on T-cell apoptosis has not been shown yet. Flow-cytometric data of blood samples from 107 children (age 3-16 yr.) who underwent cardiac surgery with (78) or without (29) CPB were analysed. Apoptotic T-lymphocytes were detected based on light scatter and surface antigen (CD45/CD3) expression (ClinExpImmunol2000;120:454). Results were compared to staining with CD3 antibodies alone and in the absence of antibodies. T-cell apoptosis rate was comparable when detected with CD45/CD3 or CD3 alone, however not in the absence of CD3. Patients with but not without CPB surgery had elevated lymphocyte apoptosis. T-cell apoptosis increased from 0.47% (baseline) to 0.97% (1 day postoperatively). In CPB patients with complication 1.10% significantly higher (ANOVA p=0.01) comparing to CPB patients without complications. Quantitation of circulating apoptotic cells based on light scatter seems an interesting new parameter for diagnosis. Increased apoptosis of circulating lymphocytes and neutrophils further contributes to the immune suppressive response to surgery with CPB. (Support: MP, Deutsche Herzstiftung, Frankfurt, Germany)

  12. Orally administered fructose increases the numbers of peripheral lymphocytes reduced by exposure of mice to gamma or SPE-like proton radiation

    Science.gov (United States)

    Romero-Weaver, A. L.; Ni, J.; Lin, L.; Kennedy, A. R.

    2014-07-01

    Exposure of the whole body or a major portion of the body to ionizing radiation can result in Acute Radiation Sickness (ARS), which can cause symptoms that range from mild to severe, and include death. One of the syndromes that can occur during ARS is the hematopoietic syndrome, which is characterized by a reduction in bone marrow cells as well as the number of circulating blood cells. Doses capable of causing this syndrome can result from conventional radiation therapy and accidental exposure to ionizing radiation. It is of concern that this syndrome could also occur during space exploration class missions in which astronauts could be exposed to significant doses of solar particle event (SPE) radiation. Of particular concern is the reduction of lymphocytes and granulocytes, which are major components of the immune system. A significant reduction in their numbers can compromise the immune system, causing a higher risk for the development of infections which could jeopardize the success of the mission. Although there are no specific countermeasures utilized for the ARS resulting from exposure to space radiation(s), granulocyte colony-stimulating factor (G-CSF) has been proposed as a countermeasure for the low number of neutrophils caused by SPE radiation, but so far no countermeasure exists for a reduced number of circulating lymphocytes. The present study demonstrates that orally administered fructose significantly increases the number of peripheral lymphocytes reduced by exposure of mice to 2 Gy of gamma- or SPE-like proton radiation, making it a potential countermeasure for this biological end-point.

  13. The architecture of neutrophil extracellular traps investigated by atomic force microscopy

    Science.gov (United States)

    Pires, Ricardo H.; Felix, Stephan B.; Delcea, Mihaela

    2016-07-01

    Neutrophils are immune cells that engage in a suicidal pathway leading to the release of partially decondensed chromatin, or neutrophil extracellular traps (NETs). NETs behave as a double edged sword; they can bind to pathogens thereby ensnaring them and limiting their spread during infection; however, they may bind to host circulating materials and trigger thrombotic events, and are associated with autoimmune disorders. Despite the fundamental role of NETs as part of an immune system response, there is currently a very poor understanding of how their nanoscale properties are reflected in their macroscopic impact. In this work, using a combination of fluorescence and atomic force microscopy, we show that NETs appear as a branching filament network that results in a substantially organized porous structure with openings with 0.03 +/- 0.04 μm2 on average and thus in the size range of small pathogens. Topological profiles typically up to 3 +/- 1 nm in height are compatible with a ``beads on a string'' model of nucleosome chromatin. Typical branch lengths of 153 +/- 103 nm appearing as rigid rods and height profiles of naked DNA in NETs of 1.2 +/- 0.5 nm are indicative of extensive DNA supercoiling throughout NETs. The presence of DNA duplexes could also be inferred from force spectroscopy and the occurrence of force plateaus that ranged from ~65 pN to 300 pN. Proteolytic digestion of NETs resulted in widespread disassembly of the network structure and considerable loss of mechanical properties. Our results suggest that the underlying structure of NETs is considerably organized and that part of its protein content plays an important role in maintaining its mesh architecture. We anticipate that NETs may work as microscopic mechanical sieves with elastic properties that stem from their DNA-protein composition, which is able to segregate particles also as a result of their size. Such a behavior may explain their participation in capturing pathogens and their association

  14. The circulation physiology of agroecosystems

    Institute of Scientific and Technical Information of China (English)

    Cao Zhiping; Richard Dawson

    2007-01-01

    This paper represents an effort to enlarge the understanding of the biophysical foundation of agroecosystems by using an analogy with the circulation of the blood in the human body. The circulation function in the human body can be represented as arterial pressure. The factors affecting arterial pressure in the human body have direct counterparts in the cultivation-husbandry system. The relationship between circulation pressure and the factors affecting that pressure in the cultivation-husbandry system are similar to the relationship between the arterial pressure and factors affecting arterial pressure in the human body. Furthermore, circulation resistance in the cultivation-husbandry system can be shown to be analogous to the calculation of peripheral resistance in the human body by Poiseuille's formula.

  15. Acoustic streaming and Sun's meridional circulation

    Science.gov (United States)

    Valverde, Jose Manuel

    2016-09-01

    A vast number of physical processes involving oscillations of a bounded viscous fluid are relevantly influenced by acoustic streaming. When this happens a steady circulation of fluid develops in a thin boundary adjacent to the interface. Some examples are refracted sound waves, a fluid inside a spherical cavity undergoing torsional oscillations or a pulsating liquid droplet. Steady streaming around circular interfaces consists of a hemispherically symmetric recirculation of fluid from the equatorial plane to the polar axes closely resembling the meridional circulation pattern observed in the Sun's convection zone that determines the solar cycle. In this paper, it is argued that the acoustic pulsations exhibited by the Sun would lead to acoustic streaming in the boundary of the convection zone. A simple estimation using a typical dominant frequency of 3 mHz and the observed surface oscillation amplitude yields a steady streaming velocity us ∼ 10 m s‑1, which is on the order of the meridional circulation velocity observed in the Sun's convection zone.

  16. RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

    DEFF Research Database (Denmark)

    Jennings, Richard T; Strengert, Monika; Hayes, Patti; El-Benna, Jamel; Brakebusch, Cord Herbert; Kubica, Malgorzata; Knaus, Ulla G

    2014-01-01

    Neutrophil responses are central to host protection and inflammation. Neutrophil activation follows a two-step process where priming amplifies responses to activating stimuli. Priming is essential for life span extension, chemotaxis and respiratory burst activity. Here we show that the cytoskeletal...... organizer RhoA suppresses neutrophil priming via formins. Premature granule exocytosis in Rho-deficient neutrophils activated numerous signaling pathways and amplified superoxide generation. Deletion of Rho altered front-to-back coordination by simultaneously increasing uropod elongation, leading edge...... neutrophils exacerbated LPS-mediated lung injury, deleting Rho in innate immune cells was highly protective in Influenza A virus infection. Hence, Rho is a key regulator of disease progression by maintaining neutrophil quiescence and suppressing hyperresponsiveness....

  17. Atmospheric Circulation of Terrestrial Exoplanets

    OpenAIRE

    Showman, Adam P.; Wordsworth, Robin D.; Merlis, Timothy M.; Kaspi, Yohai

    2013-01-01

    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical a...

  18. Is blood neutrophil-lymphocyte ratio an independent predictor of knee osteoarthritis severity?

    Science.gov (United States)

    Taşoğlu, Özlem; Bölük, Hüma; Şahin Onat, Şule; Taşoğlu, İrfan; Özgirgin, Neşe

    2016-06-01

    Knee osteoarthritis (OA) is one of the most common forms of joint disease, affecting an increasing number of people worldwide. Latest data suggests that inflammation plays a critical role in the pathogenesis of OA. There are a number of inflammatory markers like cytokins and cartilage degradation products that can be used as indicators in OA. Blood neutrophil-lymphocyte ratio (NLR) is a simple non-invasive and cost-effective marker of inflammation in various systemic diseases, but it has not been investigated in OA yet. The aim of the present study was to compare blood NLR levels in patients with severe - Kellgren and Lawrence (KL) grade 4 - knee OA and mild to moderate - KL grades 1-3 - knee OA. A total of 176 patients with knee OA were included in this cross-sectional study. KL grading was done according to the two-view (antero-posterior and lateral) plain radiography of both knees. Demographic characteristics, blood neutrophil, lymphocyte and platelet counts, erythrocyte sedimentation rate, and C-reactive protein were recorded. Blood NLR levels were calculated. In the severe knee OA group, blood NLR levels were found to be elevated as compared to the mild to moderate knee OA group. A blood NLR of ≥2.1 was taken as the cutoff based upon the receiver operating characteristics (roc). In the roc curve analysis, blood NLR ≥ 2.1 had 50 % sensitivity and 77 % specificity in predicting severe knee OA. In multivariate analysis, age and blood NLR ≥ 2.1 emerged as independent predictors of severe knee OA. The results of the present study, for the first time in the literature, suggests blood NLR as a novel and promising inflammatory marker indicating the severity of knee OA. PMID:26780447

  19. Haemophilus influenzae Infection Drives IL-17-Mediated Neutrophilic Allergic Airways Disease

    OpenAIRE

    Essilfie, Ama-Tawiah; Simpson, Jodie L.; Horvat, Jay C.; Julie A Preston; Dunkley, Margaret L.; Paul S Foster; Gibson, Peter G; Hansbro, Philip M

    2011-01-01

    A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark featu...

  20. Haemophilus influenzae infection drives IL-17-mediated neutrophilic allergic airways disease.

    OpenAIRE

    Ama-Tawiah Essilfie; Simpson, Jodie L.; Horvat, Jay C.; Julie A Preston; Dunkley, Margaret L.; Paul S Foster; Gibson, Peter G; Hansbro, Philip M

    2011-01-01

    A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark featu...

  1. Opposition between PKC Isoforms Regulates Histone Deimination and Neutrophil Extracellular Chromatin Release

    OpenAIRE

    Marko eRadic; Indira eNeeli

    2013-01-01

    In response to inflammation, neutrophils deiminate histones and externalize chromatin. Neutrophil extracellular traps (NETs) are an innate immune defense mechanism, yet NETs also may aggravate chronic inflammatory and autoimmune disorders. Activation of peptidylarginine deiminase IV (PAD4) is associated with NET release (NETosis) but the precise mechanisms of PAD4 regulation are unknown. We observed that, in human neutrophils, calcium ionophore induced histone deimination, whereas phorbol ...

  2. Fluid Shear Stress Increases Neutrophil Activation via Platelet-Activating Factor

    OpenAIRE

    Mitchell, Michael J.; Lin, Kimberly S.; King, Michael R.

    2014-01-01

    Leukocyte exposure to hemodynamic shear forces is critical for physiological functions including initial adhesion to the endothelium, the formation of pseudopods, and migration into tissues. G-protein coupled receptors on neutrophils, which bind to chemoattractants and play a role in neutrophil chemotaxis, have been implicated as fluid shear stress sensors that control neutrophil activation. Recently, exposure to physiological fluid shear stresses observed in the microvasculature was shown to...

  3. The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids

    OpenAIRE

    Ruby Yoana Murcia; Amandine Vargas; Jean-Pierre Lavoie

    2016-01-01

    Background Glucocorticoids (GCs) are the most effective drugs for the treatment of human asthma. However, a subgroup of asthmatic patients with neutrophilic airway inflammation is insensitive to GCs. Interleukin-17 (IL-17), a cytokine upregulated in the airways of a subset of human asthmatic patients, contributes to the recruitment of neutrophils and induces a glucocorticoid resistance in human airway epithelial cells. We hypothesized that IL-17 similarly activates neutrophils and contributes...

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

    OpenAIRE

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

    2015-01-01

    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 neutrop...

  5. The Effects of Pterostilbene on Neutrophil Activity in Experimental Model of Arthritis

    OpenAIRE

    Tomas Perecko; Katarina Drabikova; Antonin Lojek; Milan Ciz; Silvester Ponist; Katarina Bauerova; Radomir Nosal; Juraj Harmatha; Viera Jancinova

    2013-01-01

    It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophils in vitro. However, little is known about its effects on neutrophils during inflammation in vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model. Lewis rats were injected by a single intradermal injection of heat-killed Mycobacterium butyricum in Freund’s adjuvant to develop arthritis. Another group of arthritic animals recei...

  6. Systemic Neutrophil Activation in a Mouse Model of Ischemic Stroke and Reperfusion

    OpenAIRE

    Morrison, Helena; McKee, Dana; Ritter, Leslie

    2010-01-01

    As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest th...

  7. Commensal microbiota stimulate systemic neutrophil migration through induction of Serum amyloid A

    OpenAIRE

    Kanther, Michelle; Tomkovich, Sarah; Sun, Xiaolun; Grosser, Melinda R.; Koo, Jaseol; Flynn, Edward J.; Jobin, Christian; Rawls, John F.

    2014-01-01

    Neutrophils serve critical roles in inflammatory responses to infection and injury, and mechanisms governing their activity represent attractive targets for controlling inflammation. The commensal microbiota is known to regulate the activity of neutrophils and other leucocytes in the intestine, but the systemic impact of the microbiota on neutrophils remains unknown. Here we utilized in vivo imaging in gnotobiotic zebrafish to reveal diverse effects of microbiota colonization on systemic neut...

  8. Neutrophil Elastase Contributes to Acute Lung Injury Induced by Bilateral Nephrectomy

    OpenAIRE

    Ishii, Tomoko; DOI, Kent; Okamoto, Koji; Imamura, Mitsuru; Dohi, Makoto; Yamamoto, Kazuhiko; Fujita, Toshiro; Noiri, Eisei

    2010-01-01

    Acute kidney injury (AKI) is a serious problem in critically ill patients of intensive care units. It has been reported previously that AKI can induce acute lung injury (ALI), as well as cause injuries to other remote organs, including the lungs. Patients with AKI complicated by ALI show remarkably high mortality. ALI is characterized by neutrophil infiltration into the lung. Neutrophil elastase (NE) is a key enzyme for tissue injury caused by activated neutrophils, such as occurs in ALI. The...

  9. Diabetes primes neutrophils to undergo NETosis which severely impairs wound healing

    OpenAIRE

    Wong, Siu Ling; Demers, Melanie; Martinod, Kimberly; Gallant, Maureen; Wang, Yanming; Goldfine, Allison B.; Kahn, C. Ronald; Wagner, Denisa D.

    2015-01-01

    Wound healing is impaired in diabetes resulting in significant morbidity and mortality. Neutrophils are the main leukocytes involved in the early phase of healing. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins1. NETs, however, can also induce tissue damage. Here we show that neutrophils isolated from type 1 and type 2 diabetic humans and mice were primed to produce NETs (a process termed, N...

  10. CIRCULATION AND DISSIPATION ON HOT JUPITERS

    International Nuclear Information System (INIS)

    Many global circulation models predict supersonic zonal winds and large vertical shears in the atmospheres of short-period Jovian exoplanets. Using linear analysis and nonlinear local simulations, we investigate hydrodynamic dissipation mechanisms to balance the thermal acceleration of these winds. The adiabatic Richardson criterion remains a good guide to linear stability, although thermal diffusion allows some modes to violate it at very long wavelengths and very low growth rates. Nonlinearly, wind speeds saturate at Mach numbers ∼2 and Richardson numbers ∼-3 of the sound speed times the pressure scale height. Coarsening the numerical resolution can also increase the speed. Hence global simulations that are incapable of representing vertical turbulence and shocks, either because of reduced physics or because of limited resolution, may overestimate wind speeds. We recommend that such simulations include artificial dissipation terms to control the Mach and Richardson numbers and to capture mechanical dissipation as heat.

  11. Circulating cancer stem cells: the importance to select.

    Science.gov (United States)

    Yang, Ming-Hsin; Imrali, Ahmet; Heeschen, Christopher

    2015-10-01

    It has been demonstrated that even localized tumors without clinically apparent metastasis give rise to circulating tumor cells (CTCs). A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients' outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, 'liquid biopsy', which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis-initiating capabilities based on their stemness properties and invasiveness and thus are critical for the patients' clinical outcome. As compared to non-tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and characterizing

  12. Tropical Atmospheric Circulations with Humidity Effects

    CERN Document Server

    Hsia, Chun-Hsiung; Ma, Tian; Wang, Shouhong

    2011-01-01

    The main objective of this article is to study the effect of the moisture on the planetary scale atmospheric circulation over the tropics. The modeling we adopt is the Boussinesq equations coupled with a diffusive equation of humidity and the humidity dependent heat source is modeled by a linear approximation of the humidity. The rigorous mathematical analysis is carried out using the dynamic transition theory. In particular, we obtain the same types of transitions and hence the scenario of the El Ni\\~no mechanism as described in \\cite{MW2,MW3}. The effect of the moisture only lowers slightly the magnitude of the critical thermal Rayleigh number.

  13. Interferon-gamma coordinates CCL3-mediated neutrophil recruitment in vivo

    Directory of Open Access Journals (Sweden)

    Foster Barbara

    2009-03-01

    Full Text Available Abstract Background We have shown previously that acute infection with the respiratory pathogen, pneumonia virus of mice (PVM, results in local production of the proinflammatory chemokine, CCL3, and that neutrophil recruitment in response to PVM infection is reduced dramatically in CCL3 -/- mice. Results In this work, we demonstrate that CCL3-mediated neutrophil recruitment is coordinated by interferon-gamma (IFNγ. Neutrophil recruitment in response to PVM infection was diminished five-fold in IFNγ receptor gene-deleted mice, although neutrophils from IFNγR -/- mice expressed transcripts for the CCL3 receptor, CCR1 and responded functionally to CCL3 ex vivo. Similarly, in the absence of PVM infection, CCL3 overexpression alone could not elicit neutrophil recruitment in the absence of IFNγ. Interestingly, although supplemental IFNγ restored neutrophil recruitment and resulted in a sustained weight loss among CCL3-overexpressing IFNγ -/- mice, CCL3-mediated neutrophil recruitment alone did not result in the pulmonary edema or respiratory failure characteristic of severe viral infection, suggesting that CCL3 and IFN-γ together are sufficient to promote neutrophil recruitment but not pathologic activation. Conclusion Our findings reveal a heretofore unrecognized hierarchical interaction between the IFNγ and CCL3, which demonstrate that IFNγ is crucial for CCL3-mediated neutrophil recruitment in vivo.

  14. The effect of midazolam on neutrophil mitogen-activated protein kinase.

    LENUS (Irish Health Repository)

    Ghori, Kamran

    2010-06-01

    Neutrophil p38 mitogen-activated protein kinase (MAPK) is a key enzyme in the intracellular signalling pathway that is responsible for many neutrophil functions, which are important in neutrophil-endothelial interaction. The imidazole compounds are inhibitors of this enzyme system. The objectives of this in-vitro investigation were to examine the effect of midazolam on neutrophil p38 MAPK activation (phosphorylation) following in-vitro ischaemia-reperfusion injury, and the expression of adhesion molecule CD11b\\/CD18.

  15. MET is required for the recruitment of anti-tumoural neutrophils.

    Science.gov (United States)

    Finisguerra, Veronica; Di Conza, Giusy; Di Matteo, Mario; Serneels, Jens; Costa, Sandra; Thompson, A A Roger; Wauters, Els; Walmsley, Sarah; Prenen, Hans; Granot, Zvi; Casazza, Andrea; Mazzone, Massimiliano

    2015-06-18

    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases. PMID:25985180

  16. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels; Nordsmark, Marianne; Lundbeck, Finn; von der Maase, Hans

    2009-01-01

    PURPOSE: We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 121 consecutive patients....... CONCLUSION: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC....... who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated. RESULTS: The...

  17. Observational Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

    Science.gov (United States)

    2014-06-11

    Other Specified Inflammatory Disorders of Skin or Subcutaneous Tissue; Pyoderma Gangrenosum; Erosive Pustular Dermatosis of the Scalp; Sweet's Syndrome; Behcet's Disease; Bowel-associated Dermatosis-arthritis Syndrome; Pustular Psoriasis; Acute Generalized Exanthematous Pustulosis; Keratoderma Blenorrhagicum; Sneddon-Wilkinson Disease; IgA Pemphigus; Amicrobial Pustulosis of the Folds; Infantile Acropustulosis; Transient Neonatal Pustulosis; Neutrophilic Eccrine Hidradenitis; Rheumatoid Neutrophilic Dermatitis; Neutrophilic Urticaria; Still's Disease; Erythema Marginatum; Unclassified Periodic Fever Syndromes / Autoinflammatory Syndromes; Dermatitis Herpetiformis; Linear IgA Bullous Dermatosis; Bullous Systemic Lupus Erythematosus; Inflammatory Epidermolysis Bullosa Aquisita; Neutrophilic Dermatosis of the Dorsal Hands (Pustular Vasculitis); Small Vessel Vasculitis Including Urticarial Vasculitis; Erythema Elevatum Diutinum; Medium Vessel Vasculitis

  18. Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Catherine W M Ong

    2015-05-01

    Full Text Available Pulmonary cavities, the hallmark of tuberculosis (TB, are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8 secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.

  19. Helicobacter pylori neutrophil activating protein as target for new drugs against H. pylori inflammation

    Science.gov (United States)

    Choli-Papadopoulou, Theodora; Kottakis, Filippos; Papadopoulos, Georgios; Pendas, Stefanos

    2011-01-01

    Helicobacter pylori (H. pylori) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer. Within this work we present the implication of C-terminal region of H. pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evidence that the C-terminal region of H. pylori activating protein is indispensable for neutrophil adhesion to endothelial cells, a step necessary to H. pylori inflammation. In addition we show that arabino galactan proteins derived from chios mastic gum, the natural resin of the plant Pistacia lentiscus var. Chia inhibit neutrophil activation in vitro. PMID:21677824

  20. Granule swelling and cleavage of mitogen-activated protein kinases in human neutrophils undergoing apoptosis

    International Nuclear Information System (INIS)

    Extracellular signal-regulated kinase and p38 have been shown to be cleaved in human neutrophils undergoing apoptosis induced by tumor necrosis factor-α and cycloheximide. However, the cleavage products of these molecules were undetected when apoptotic neutrophils were pretreated with phenylmethylsulfonyl fluoride or disrupted by nitrogen cavitation before preparation of cell lysates. The electron microscopy revealed that granules in apoptotic neutrophils were significantly swollen than those in control cells. These findings suggest that granule membrane may become destabilized during neutrophil apoptosis, leading to rapid proteolysis of these molecules by granule-derived serine proteases during preparation of cell lysates with the conventional lysis buffer.

  1. 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. PMID:27001541

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

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    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.

  3. Roscovitine-induced apoptosis in neutrophils and neutrophil progenitors is regulated by the Bcl-2-family members Bim, Puma, Noxa and Mcl-1.

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    Sanjivan Gautam

    Full Text Available Neutrophil granulocyte (neutrophil apoptosis plays a key role in determining inflammation in infectious and non-infectious settings. Recent work has shown that inhibitors of cyclin-dependent kinases (cdk such as roscovitine can potently induce neutrophil apoptosis and reduce inflammation. Using a conditional Hoxb8-expression system we tested the participation of Bcl-2-family proteins to roscovitine-induced apoptosis in mouse neutrophils and in neutrophil progenitor cells. Bcl-2 strongly protected against roscovitine-induced apoptosis in neutrophils. The isolated loss of either Bim or noxa provided significant, partial protection while protection through combined loss of Bim and noxa or Bim and Puma was only slightly greater than this individual loss. The only substantial change in protein levels observed was the loss of Mcl-1, which was not transcriptional and was inhibited by proteasome blockade. In progenitor cells there was no protection by the loss of Bim alone but substantial protection by the loss of both Bim and Puma; surprisingly, strongest protection was seen by the isolated loss of noxa. The pattern of protein expression and Mcl-1-regulation in progenitor cells was very similar to the one observed in differentiated neutrophils. In addition, roscovitine strongly inhibited proliferation in progenitor cells, associated with an accumulation of cells in G2/M-phase.

  4. Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses

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    Koga Hikari

    2013-01-01

    Full Text Available Abstract Background Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR in previously sensitized and challenged mice. Methods BALB/c mice were sensitized and challenged (primary with ovalbumin (OVA. Six weeks later, a single OVA aerosol (secondary challenge was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge. Results Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-β1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice. Conclusion These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the

  5. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  6. Staphylococcus epidermidis strategies to avoid killing by human neutrophils.

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    Gordon Y C Cheung

    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.

  7. 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.

  8. Neutrophil elastase and proteinase 3 trafficking routes in myelomonocytic cells

    International Nuclear Information System (INIS)

    Neutrophil elastase (NE) and proteinase 3 (PR3) differ in intracellular localization, which may reflect different trafficking mechanisms of the precursor forms when synthesized at immature stages of neutrophils. To shed further light on these mechanisms, we compared the trafficking of precursor NE (proNE) and precursor PR3 (proPR3). Like proNE [1], proPR3 interacted with CD63 upon heterologous co-expression in COS cells but endogenous interaction was not detected although cell surface proNE/proPR3/CD63 were co-endocytosed in myelomonocytic cells. Cell surface proNE/proPR3 turned over more rapidly than cell surface CD63 consistent with processing/degradation of the pro-proteases but recycling of CD63. Colocalization of proNE/proPR3/CD63 with clathrin and Rab 7 suggested trafficking through coated vesicles and late endosomes. Partial caveolar trafficking of proNE/CD63 but not proPR3 was suggested by colocalization with caveolin-1. Blocking the C-terminus of proNE/proPR3 by creating a fusion with FK506 binding protein inhibited endosomal re-uptake of proNE but not proPR3 indicating 'proC'-peptide-dependent structural/conformational requirements for proNE but not for proPR3 endocytosis. The NE aminoacid residue Y199 of a proposed NE sorting motif that interacts with AP-3 [2] was not required for proNE processing, sorting or endocytosis in rat basophilic leukemia (RBL) cells expressing heterologous Y199-deleted proNE; this suggests operation of another AP-3-link for proNE targeting. Our results show intracellular multi-step trafficking to be different between proNE and proPR3 consistent with their differential subcellular NE/PR3 localization in neutrophils.

  9. Short-Term Effects of Oral Feeding Jujube Ziziphus Solution before a Single Session of Circuit Resistance Exercise on Apoptosis of Human Neutrophil

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    Seyed Morteza Tayebi

    2014-04-01

    Full Text Available The aim of present research was the effect of short-term use of edible solution of jujube one week before a single session of circuit resistance exercise on neutrophil apoptosis of male students of physical education. 14 young male volunteer students were divided into two groups of placebo (n=7, aged 24.50±2.50, height 171.17±1.70, and weight 67.51±4.92 and jujube solution (n=7, aged 25.25±1.31, height 179.75±3.63, weight 74.07±5.78 at random, performing one circuit resistance exercise (9 moves/stops, 30 seconds for each exercise, 3 nonstop sets with a 3-minute active recession between sets, 10-14 repetitions, and an intensity of 70% maximum repetition. Subjects received placebo and jujube solutions (0.5 g/kgbody weight in 2.5cc of distilled water as long as 7 days at certain times and double-blind. Blood samples were collected 30 minutes before, immediately, and 2 hours after the exercise for separation and counting the number of neutrophils, and neutrophil apoptosis was determined through AnexinV-FITC kit and flow cytometric method. The results indicated the significant response of initial apoptosis neutrophils to one course of activity by jujube group. However, different responses were observed between two groups of placebo and jujube during the recession after training. Unlike placebo group, the response was significantly lower with a greater decrease after training in jujube group. However, necrosis/delayed apoptosis neutrophils significantly increased in placebo group after 2 hours, while this change was not observed in jujube group. At the end of a 2-hour recession, delayed apoptosis neutrophils significantly decreased in both placebo and jujube groups. The present findings indicate that one-session resistance activity is not very effective after pretreatment with jujube solution during one week. Perhaps this useful effect of jujube can be explained by existing glucose compounds and amino acids which could provide neutrophils with

  10. sup 111 Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Haslett, C.; Shen, A.S.; Feldsien, D.C.; Allen, D.; Henson, P.M.; Cherniack, R.M. (National Jewish Center for Immunology and Respiratory Medicine, Denver, CO (USA))

    1989-09-01

    Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung region of interest (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis.

  11. 111Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy

    International Nuclear Information System (INIS)

    Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung region of interest (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis

  12. 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 metrics with simultaneously acquired measurements of transepithelial electrical resistance (TEER), a measure of membrane integrity that decreases when neutrophils create openings in the epithelium to permit migration. Preliminary

  13. 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 immune diseases.

  14. The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids

    Science.gov (United States)

    Murcia, Ruby Yoana; Vargas, Amandine; Lavoie, Jean-Pierre

    2016-01-01

    Background Glucocorticoids (GCs) are the most effective drugs for the treatment of human asthma. However, a subgroup of asthmatic patients with neutrophilic airway inflammation is insensitive to GCs. Interleukin-17 (IL-17), a cytokine upregulated in the airways of a subset of human asthmatic patients, contributes to the recruitment of neutrophils and induces a glucocorticoid resistance in human airway epithelial cells. We hypothesized that IL-17 similarly activates neutrophils and contributes to their persistence in the asthmatic airways in spite of glucocorticoid therapy. Objective To determine whether IL-17 directly activates neutrophils and whether this response is attenuated by GCs. Methods Neutrophils were isolated from the blood of horses and incubated in the presence of recombinant equine IL-17, LPS and dexamethasone. mRNA and protein expression of IL-17 receptors (IL-17RA/IL-17RC) were assessed by qPCR and immunoblot, respectively. Pro-inflammatory cytokine expression, cell viability and apoptosis were determined by qPCR, Trypan Blue exclusion test, and flow cytometry, respectively. Results Equine neutrophils express both IL-17RA and IL-17RC at the mRNA and protein levels. Neutrophil stimulation with IL-17 increases the mRNA expression of IL-8, which is not attenuated by dexamethasone (p = 0.409). Also, neutrophil viability is significantly increased (p<0.0001) by IL-17 in the presence of LPS when compared to LPS alone. Flow cytometry and light microscopy revealed that LPS-induced apoptosis is decreased by IL-17 (p = 0.02 and p = 0.006 respectively). Conclusion These results indicate that IL-17 directly activates equine neutrophils at 24 hours, and that the expression of IL-8 thus induced is not attenuated by GCs. Additionally, IL-17 increases neutrophil viability and decreases apoptosis. These findings suggest an important role of IL-17 in pulmonary persistence of neutrophils in the asthmatic airways. PMID:27138006

  15. of Matrix Metalloproteinase-9 and Neutrophil Gelatinase-Associated Lipocalin

    Directory of Open Access Journals (Sweden)

    De Caridi Giovanni

    2015-01-01

    Full Text Available The association of an axillary artery aneurysm and an abdominal aortic aneurysm is extremely rare. In this study, we describe this association in a 69 year-old-man. We measured this patient’s metalloproteinases (MMPs and Neutrophil Gelatinase - Associated Lipocalin (NGAL levels over a three years period before the abdominal aortic aneurysm rupture. We speculate that high serium levels of MMPs and NGAL may have a prognostic role and may predict aneurysm rupture in patients with an uncommon association of arterial aneurysms.

  16. Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.

    Science.gov (United States)

    Craig, Morgan; Humphries, Antony R; Nekka, Fahima; Bélair, Jacques; Li, Jun; Mackey, Michael C

    2015-11-21

    The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy. PMID:26343861

  17. Circulating microRNA expression pattern separates patients with anti-neutrophil cytoplasmic antibody-associated vasculitis from healthy controls

    DEFF Research Database (Denmark)

    Skoglund, C.; Carlsen, A.; Weiner, M.;

    2015-01-01

    Objective. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV...

  18. Design realization towards the qualification test of ITER cold circulator

    Science.gov (United States)

    Bhattacharya, R.; Sarkar, B.; Vaghela, H.; Patel, P.; Das, J.; Srinivasa, M.; Shukla, V.

    2015-12-01

    Cold circulators, part of ITER Cryo-distribution system, have now reached to a stage of final qualification to demonstrate the design to cater the maximum mass flow and operational demands of the toroidal field (TF) superconducting magnet of ITER with a very high isentropic efficiency. The design for the two numbers of TF cold circulators are now complete gratifying additionally the operational requirements of poloidal field & central solenoid superconducting magnet as well as the cryopumps towards the fulfilment of standardization aspects. Management of physical and functional interfaces has been identified as one the most critical aspect towards the performance of cold circulator. All the interfaces of cold circulators have been analysed with the help of optimized interfacing parameters of Test Auxiliary Cold Box (TACB) and cryogenic test facility at JAEA, Japan during the course of design finalization. Testing at the warm conditions after completion of precise manufacturing of cold circulators has been performed before integrating into the TACB to fulfil the Japanese as well as European regulatory requirements simultaneously. The paper elaborates the methodology of interface management and control, analysis performed towards the interface management and preliminary test results towards the qualification test of the ITER cold circulator.

  19. Atmospheric Circulation of Terrestrial Exoplanets

    CERN Document Server

    Showman, Adam P; Merlis, Timothy M; Kaspi, Yohai

    2013-01-01

    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical and dynamical conditions, only a small fraction of which have yet been explored in detail. Our approach is to lay out the fundamental dynamical principles governing the atmospheric circulation on terrestrial planets--broadly defined--and show how they can provide a foundation for understanding the atmospheric behavior of these worlds. We first survey basic atmospheric dynamics, including the role of geostrophy, baroclinic instabilities, and jets in the strongly rotating regime (the "extratropics") and the role of the Hadle...

  20. Circulation and Dissipation on Hot Jupiters

    CERN Document Server

    Li, Jason

    2010-01-01

    Many global circulation models predict supersonic zonal winds and large vertical shears in the atmospheres of short-period jovian exoplanets. Using linear analysis and nonlinear local simulations, we investigate hydrodynamic dissipation mechanisms to balance the thermal acceleration of these winds. The adiabatic Richardson criterion remains a good guide to linear stability, although thermal diffusion allows some modes to violate it at very long wavelengths and very low growth rates. Nonlinearly, wind speeds saturate at Mach numbers $\\approx 2$ and Richardson numbers $\\lesssim 1/4$ for a broad range of plausible diffusivities and forcing strengths. Turbulence and vertical mixing, though accompanied by weak shocks, dominate the dissipation, which appears to be the outcome of a recurrent Kelvin-Helmholtz instability. An explicit shear viscosity, as well as thermal diffusivity, is added to ZEUS to capture dissipation outside of shocks. The wind speed is not monotonic nor single valued for shear viscosities larger...