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Sample records for lymphocytes monocytes eosinophils

  1. Short-term effects of regional irradiation on lymphocytes, T lymphocytes and eosinophils

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    Chazarin, C.; Roche, H.; Bugat, R.; Pris, F.

    1983-01-01

    Twenty-three cancer patients treated only by regional irradiation were studied. Radiotherapy was delivered to the pelvis in 14 patients and to the mediastinum in 9. T lymphocytes were evaluated with the Jondal technique. Before treatment, lymphocyte counts were identical in patients and control. Decreases in total lymphocytes and T lymphocytes became significant in both groups after 40 Gy. Significant rises in eosinophil counts were found only after abdominal irradiation and seemed unrelated to variations in lymphocyte counts [fr

  2. ROLE OF MONOCYTES AND EOSINOPHILS IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION

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    Role of Monocytes and Eosinophils in Respiratory Syncytial Virus (RSV) InfectionJoleen M. Soukup and Susanne Becker US Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711;...

  3. Usefulness of Eosinophil-Lymphocyte Ratio to Predict Stent Restenosis

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    Mehmet Zihni Bilik

    2016-06-01

    Full Text Available Objective: Stent restenosis (SR is an important compli­cation of percutaneous coronary intervention. There are many studies explored the relation of eosinophils with SR, however, there is no data about relationship between eo­sinophil-lymphocyte ratio (ELR and SR. In this study we aimed to investigate the relationship between the value of ELR on admission and SR. Methods: The study was included 314 patients who had been applied a coronary stent implantation and they were admitted to cardiology clinic with stabile angina and un­derwent repeat coronary angiography. The data obtained from patients were analyzed retrospectively. The patient group was consisted of 197 patients who were diagnosed as SR, and the control group was consisted of 117 pa­tients whose stents were patent angiographically. Results: The groups were similar in terms of age, gender, hypertension, diabetes mellitus, LDL-C, HDL-C, platelet count, platelet-lymphocyte ratio (PLR, hemoglobin and left ventricle ejection fraction (LVEF. White blood cell (WBC, neutrophil, eosinophil, C-reactive protein (CRP, ELR and neutrophil-lymphocyte ratio (NLR on admission were higher in the SR group compared to the controls. All patients were categorized into two groups according to ELR values and SR was more frequent in the high ELR group compared to low ELR group. An ELR value of ≥0.745 predicted SR with 64% sensitivity and 61% specif­ity. Conclusion: In this study ELR was found statistically higher in SR patients compared to the controls. Accord­ing to our data ELR as an inexpensive and easy method, may contribute to determination of high risk patients and increased ELR can be used as a predictor of SR.

  4. Monocyte-lymphocyte fusion induced by the HIV-1 envelope generates functional heterokaryons with an activated monocyte-like phenotype

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    Martínez-Méndez, David; Rivera-Toledo, Evelyn; Ortega, Enrique; Licona-Limón, Ileana; Huerta, Leonor, E-mail: leonorhh@biomedicas.unam.mx

    2017-03-01

    Enveloped viruses induce cell-cell fusion when infected cells expressing viral envelope proteins interact with target cells, or through the contact of cell-free viral particles with adjoining target cells. CD4{sup +} T lymphocytes and cells from the monocyte-macrophage lineage express receptors for HIV envelope protein. We have previously reported that lymphoid Jurkat T cells expressing the HIV-1 envelope protein (Env) can fuse with THP-1 monocytic cells, forming heterokaryons with a predominantly myeloid phenotype. This study shows that the expression of monocytic markers in heterokaryons is stable, whereas the expression of lymphoid markers is mostly lost. Like THP-1 cells, heterokaryons exhibited FcγR-dependent phagocytic activity and showed an enhanced expression of the activation marker ICAM-1 upon stimulation with PMA. In addition, heterokaryons showed morphological changes compatible with maturation, and high expression of the differentiation marker CD11b in the absence of differentiation-inducing agents. No morphological change nor increase in CD11b expression were observed when an HIV-fusion inhibitor blocked fusion, or when THP-1 cells were cocultured with Jurkat cells expressing a non-fusogenic Env protein, showing that differentiation was not induced merely by cell-cell interaction but required cell-cell fusion. Inhibition of TLR2/TLR4 signaling by a TIRAP inhibitor greatly reduced the expression of CD11b in heterokaryons. Thus, lymphocyte-monocyte heterokaryons induced by HIV-1 Env are stable and functional, and fusion prompts a phenotype characteristic of activated monocytes via intracellular TLR2/TLR4 signaling. - Highlights: • Jurkat T cells expressing the HIV-1 envelope fuse with THP-1 monocytes. • Heterokaryons display a dominant myeloid phenotype and monocyte function. • Heterokaryons exhibit activation features in the absence of activation agents. • Activation is not due to cell-cell interaction but requires cell-cell fusion. • The

  5. Monocyte-lymphocyte fusion induced by the HIV-1 envelope generates functional heterokaryons with an activated monocyte-like phenotype

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    Martínez-Méndez, David; Rivera-Toledo, Evelyn; Ortega, Enrique; Licona-Limón, Ileana; Huerta, Leonor

    2017-01-01

    Enveloped viruses induce cell-cell fusion when infected cells expressing viral envelope proteins interact with target cells, or through the contact of cell-free viral particles with adjoining target cells. CD4"+ T lymphocytes and cells from the monocyte-macrophage lineage express receptors for HIV envelope protein. We have previously reported that lymphoid Jurkat T cells expressing the HIV-1 envelope protein (Env) can fuse with THP-1 monocytic cells, forming heterokaryons with a predominantly myeloid phenotype. This study shows that the expression of monocytic markers in heterokaryons is stable, whereas the expression of lymphoid markers is mostly lost. Like THP-1 cells, heterokaryons exhibited FcγR-dependent phagocytic activity and showed an enhanced expression of the activation marker ICAM-1 upon stimulation with PMA. In addition, heterokaryons showed morphological changes compatible with maturation, and high expression of the differentiation marker CD11b in the absence of differentiation-inducing agents. No morphological change nor increase in CD11b expression were observed when an HIV-fusion inhibitor blocked fusion, or when THP-1 cells were cocultured with Jurkat cells expressing a non-fusogenic Env protein, showing that differentiation was not induced merely by cell-cell interaction but required cell-cell fusion. Inhibition of TLR2/TLR4 signaling by a TIRAP inhibitor greatly reduced the expression of CD11b in heterokaryons. Thus, lymphocyte-monocyte heterokaryons induced by HIV-1 Env are stable and functional, and fusion prompts a phenotype characteristic of activated monocytes via intracellular TLR2/TLR4 signaling. - Highlights: • Jurkat T cells expressing the HIV-1 envelope fuse with THP-1 monocytes. • Heterokaryons display a dominant myeloid phenotype and monocyte function. • Heterokaryons exhibit activation features in the absence of activation agents. • Activation is not due to cell-cell interaction but requires cell-cell fusion. • The

  6. Eosinophils.

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    Radonjic-Hösli, Susanne; Simon, Hans-Uwe

    2014-01-01

    In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather than just a developmental stage. It was, however, not until 1879, when Paul Ehrlich introduced a method to distinguish granular cells by the staining properties of their granules, that a classification became possible. An intensive staining for eosin, among other aniline dyes, was eponymous for the coarsely granular cell type, which thereupon became referred to as eosinophil granulocyte. Eosinophilia had already been described in many diseases by the late 19th century. The role of these cells, however, today remains a matter of continuing speculation and investigation. Many functions have been attributed to the eosinophil over the years, often linked to increasing knowledge about the granular and cytoplasmatic contents. A better understanding of the regulatory mechanisms of eosinopoiesis has led to the development of knock-out mice strains as well as therapeutic strategies for reducing the eosinophil load in patients. The effect of these therapeutics and the characterization of the knock-out phenotypes have led to a great increase in the knowledge of the role of the eosinophil in disease. Today we think of the eosinophil as a multifunctional cell involved in host defense, tissue damage and remodeling, as well as immunomodulation. © 2014 S. Karger AG, Basel.

  7. Reference ranges for blood concentrations of eosinophils and monocytes during the neonatal period defined from over 63 000 records in a multihospital health-care system.

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    Christensen, R D; Jensen, J; Maheshwari, A; Henry, E

    2010-08-01

    Blood concentrations of eosinophils and monocytes are part of the complete blood count. Reference ranges for these concentrations during the neonatal period, established by very large sample sizes and modern methods, are needed for identifying abnormally low or high values. We constructed reference ranges for eosinophils per microl and monocytes per microl among neonates of 22 to 42 weeks of gestation, on the day of birth, and also during 28 days after birth. Data were obtained from archived electronic records over an eight and one-half-year period in a multihospital health-care system. In keeping with the reference range concept, values were excluded from neonates with a diagnosis of infection or necrotizing enterocolitis (NEC). Eosinophils and monocytes per microl of blood were electronically retrieved from 96 162 records, of which 63 371 that lacked a diagnosis of infection or NEC were included in this reference range report. The mean value for eosinophils per microl on the day of birth increased linearly between 22 and 42 weeks of gestation, as did the 5 and 95% values. The reference range at 40 weeks was 140 to 1300 microl(-1) (mean 550 microl(-1)). Similarly, the mean value for monocytes increased linearly over this interval, with a reference range at 40 weeks of 300 to 3300 microl(-1) (mean 1400 microl(-1)). Over the first 4 weeks after birth, no appreciable change was observed in 5% limit and mean eosinophil count, with a slight increase in the 95% limit in week 4. A slight increase in monocyte count was observed during the first 2 weeks after birth. The results of this analysis describe reference ranges for blood concentrations of eosinophils and monocytes during the neonatal period. Additional study is needed for determining the relevance of values falling outside the reference range.

  8. Immunogenetic analysis of cellular interactions governing the recruitment of T lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology

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    Doherty, P.C.; Ceredig, R.; Allan, J.E.

    1988-01-01

    The Lyt2+ class I major histocompatibility complex (MHC)-restricted virus-immune T cells that induce murine lymphocytic choriomeningitis (LCM) are targeted onto radiation-resistant cells in the central nervous system of virus-infected mice. The use of appropriate bone marrow radiation chimeras as LCM virus-infected, (immunosuppressed recipients for immune T-cell transfer has established that, though bone marrow-derived cells can stimulate virus-specific cytotoxic T lymphocytes (CTL) in spleen, they do not reconstitute the barrier to T-cell recruitment from blood to cerebrospinal fluid. This is true for chimeras made up to 8 months previously, even though the inflammatory monocytes and macrophages in such chimeras are all of donor bone marrow origin. Radiation-resistant cells in the spleens of these chimeras are also still able to further stimulate virus-immune CTL. There is no requirement for H-2 compatibility between virus-immune T lymphocytes and secondarily recruited monocytes, or T cells of an inappropriate specificity. The key event in LCM immunopathology may thus be localization of T cells to the antigen-presenting endothelium in brain, leading to the secretion of mediators that promote the nonspecific recruitment of monocytes and other T cells

  9. Monocyte and lymphocyte surface molecules in severe sepsis and non-septic critically ill Patients.

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    Jämsä, Joel; Syrjälä, Hannu; Huotari, Virva; Savolainen, Eeva-Riitta; Ala-Kokko, Tero

    2017-06-01

    The aim of the present study was to investigate whether expression of monocyte and lymphocyte surface molecules differs between patients with severe sepsis and non-septic patients treated in the intensive care unit (ICU). The expression of monocyte CD14, CD40, CD80 and HLA-DR, and lymphocyte CD69 were analyzed using quantitative flow cytometry on three consecutive days in 27 patients with severe sepsis and in 15 non-septic patients. Receiver operating characteristic analyses were performed and each corresponding area under the curve (AUC) was determined. The results showed that the expression levels of CD40 on monocytes and CD69 on CD4+ T cells and on natural killer (NK) cells were highest in patients with severe sepsis (p sepsis and positive blood culture compared with those with negative blood culture (p sepsis detection were 0.836 for CD40, 0.872 for CD69 on NK cells, and 0.795 for CD69 on CD4+ T cells. These findings suggest that monocyte CD40 and CD69 on NK cells and CD4+ T cells could prove useful for new approaches in the identification of severe sepsis in the ICU. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  10. Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer.

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    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Ohtani, Hiroshi; Sakurai, Katsunobu; Yamazoe, Sadaaki; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

    2015-09-14

    To evaluate the prognostic significance of the lymphocyte to monocyte ratio (LMR) in patients with unresectable metastatic colorectal cancer who received palliative chemotherapy. A total of 104 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy were enrolled. The LMR was calculated from blood samples by dividing the absolute lymphocyte count by the absolute monocyte count. Pre-treatment LMR values were measured within one week before the initiation of chemotherapy, while post-treatment LMR values were measured eight weeks after the initiation of chemotherapy. The median pre-treatment LMR was 4.16 (range: 0.58-14.06). We set 3.38 as the cut-off level based on the receiver operating characteristic curve. Based on the cut-off level of 3.38, 66 patients were classified into the high pre-treatment LMR group and 38 patients were classified into the low pre-treatment LMR group. The low pre-treatment LMR group had a significantly worse overall survival rate (P = 0.0011). Moreover, patients who demonstrated low pre-treatment LMR and normalization after treatment exhibited a better overall survival rate than the patients with low pre-treatment and post-treatment LMR values. The lymphocyte to monocyte ratio is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy.

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

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    Thang Thanh Phan

    2018-04-01

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

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

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    Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer

    2017-10-01

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

  13. Ibrutinib modifies the function of monocyte/macrophage population in chronic lymphocytic leukemia.

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    Fiorcari, Stefania; Maffei, Rossana; Audrito, Valentina; Martinelli, Silvia; Ten Hacken, Elisa; Zucchini, Patrizia; Grisendi, Giulia; Potenza, Leonardo; Luppi, Mario; Burger, Jan A; Deaglio, Silvia; Marasca, Roberto

    2016-10-04

    In lymphoid organs, nurse-like cells (NLCs) show properties of tumor-associated macrophages, playing a crucial role in chronic lymphocytic leukemia (CLL) cell survival. Ibrutinib, a potent inhibitor of Bruton's tyrosine kinase (BTK), is able to counteract pro-survival signals in CLL cells. Since the effects on CLL cells have been studied in the last years, less is known about the influence of ibrutinib on NLCs properties. We sought to determine how ibrutinib modifies NLCs functions focusing on the balance between immunosuppressive and inflammatory features. Our data show that ibrutinib targets BTK expressed by NLCs modifying their phenotype and function. Treatment with ibrutinib reduces the phagocytic ability and increases the immunosuppressive profile of NLCs exacerbating the expression of M2 markers. Accordingly, ibrutinib hampers LPS-mediated signaling, decreasing STAT1 phosphorylation, while allows IL-4-mediated STAT6 phosphorylation. In addition, NLCs treated with ibrutinib are able to protect CLL cells from drug-induced apoptosis partially through the secretion of IL-10. Results from patient samples obtained prior and after 1 month of treatment with ibrutinib show an accentuation of CD206, CD11b and Tie2 in the monocytic population in the peripheral blood. Our study provides new insights into the immunomodulatory action of ibrutinib on monocyte/macrophage population in CLL.

  14. The prognostic value of lymphocyte-to-monocyte ratio in retinopathy of prematurity

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    Yu-Xiang Hu

    2017-11-01

    Full Text Available AIM: To evaluate the associations between development of retinopathy of prematurity (ROP and serum lymphocyte-to-monocyte ratio (LMR, neutrophil-to-lymphocyte ratio (NLR, and platelet-to-lymphocyte ratio (PLR. METHODS: A retrospective cohort study was performed, involving infants who were screened for ROP from January 2015 to December 2015. Preterm newborns of ≤32 gestational weeks with ROP were enrolled as the observation group, and non-ROP infants were enrolled as the control group, whose complete blood cell were measured within the first 24h of life. The levels of NLR, LMR and PLR were determined in all groups. The data obtained were analyzed using univariate and multivariate logistic regression analysis. RESULTS: In this study, 40 cases of ROP were enrolled and 40 cases of non-ROP as controls. The LMR levels were significantly higher (P<0.001 in ROP group (3.96±1.16 compared to non-ROP group (2.85±0.79. The NLR levels were significantly lower (P=0.035 in ROP group {median [interquartile range (IQR], 0.88 (0.67-1.46} compared to non-ROP group [median (IQR, 1.20 (0.85-1.89]. The median PLR values were 61.99 (IQR, 50.23-75.98 in ROP group and 69.24 (IQR, 55.52-88.12 in non-ROP group (P=0.104. Logistic regression analysis suggested that LMR was an independent risk factor for ROP (OR: 0.275; 95% CI: 0.134-0.564; P=0.001. CONCLUSION: The findings demonstrate that higher LMR is independently and significantly associated with the development of ROP, and the LMR may be invoked as a predictive tool for identifying risk for ROP.

  15. Gambaran Sel Eosinofil, Monosit, dan Basofil Setelah Pemberian Spirulina pada Ayam yang Diinfeksi Virus Flu Burung (OBSERVATION OF EOSINOPHILS, MONOCYTES, AND BASOPHILS AFTER TREATED WITH SPIRULINA IN CHICKENS THAT INFECTED WITH AVIAN INFLUENZA VIRUS

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    Widya Paramita Lokapirnasari

    2015-05-01

    Full Text Available High Pathogenecity Avian Influenza (HPAI viruses have high virulence and can frequently causesudden death on birds. The aims of this research was to know the role of Spirulina to a number ofmonocytes and lymphocytes in the blood of chickens which infected with the H5N1 virus. This researchconsisted of three levels of treatment in which each level given Spirulina 0%, 10%, 20% in the fresh wateralgae as drinking water. Each treatment consisted of seven replicates, and the treatment was done sincethe chickens at age 19 until 44 days ( for 25 days. Artificial infection of the chickens with the virus waschallenged by using AI (H5N1 104 EID 50 (A/Ck/Indonesia/BL/03 with route to the respiratory tract (nosedrops 0,1 mL starting on day 19. The results showed that there were a significant difference (p<0.05 ontreatment that given Spirulina at doses of 0%, 10% and 20% for the number ofn monocytes, eosinophils,whereas no significant difference (p > 0.05 was observed in basophils.

  16. Immature dendritic cells generated from cryopreserved human monocytes show impaired ability to respond to LPS and to induce allogeneic lymphocyte proliferation.

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    Guilherme Ferreira Silveira

    Full Text Available Dendritic cells play a key role in the immune system, in the sensing of foreign antigens and triggering of an adaptive immune response. Cryopreservation of human monocytes was investigated to understand its effect on differentiation into immature monocyte-derived dendritic cells (imdDCs, the response to inflammatory stimuli and the ability to induce allogeneic lymphocyte proliferation. Cryopreserved (crp-monocytes were able to differentiate into imdDCs, albeit to a lesser extent than freshly (frh-obtained monocytes. Furthermore, crp-imdDCs had lower rates of maturation and cytokine/chemokine secretion in response to LPS than frh-imdDCs. Lower expression of Toll-like receptor 4 (at 24 and 48 h and higher susceptibility to apoptosis in crp-imdDCs than in fresh cells would account for the impaired maturation and cytokine/chemokine secretion observed. A mixed leukocyte reaction showed that lymphocyte proliferation was lower with crp-imdDCs than with frh-imdDCs. These findings suggested that the source of monocytes used to generate human imdDCs could influence the accuracy of results observed in studies of the immune response to pathogens, lymphocyte activation, vaccination and antigen sensing. It is not always possible to work with freshly isolated monocytes but the possible effects of freezing/thawing on the biology and responsiveness of imdDCs should be taken into account.

  17. Eosinophilic Disorders

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    ... eosinophils per microliter of blood). Low number of eosinophils A low number of eosinophils in the blood ( ... the normal number of eosinophils. High number of eosinophils The most common causes of a high number ...

  18. Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer

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    Jiangdong Xiang

    2017-02-01

    Full Text Available PURPOSE: The monocyte-to-lymphocyte ratio (MLR has been shown to be associated with the prognosis of various solid tumors. This study sought to evaluate the important value of the MLR in ovarian cancer patients. METHODS: A total of 133 ovarian cancer patients and 43 normal controls were retrospectively reviewed. The patients' demographics were analyzed along with clinical and pathologic data. The counts of peripheral neutrophils, lymphocytes, monocytes, and platelets were collected and used to calculate the MLR, neutrophil-to-lymphocyte ratio (NLR. and platelet-to-lymphocyte ratio (PLR. The optimal cutoff value of the MLR was determined by using receiver operating characteristic curve analysis. We compared the MLR, NLR, and PLR between ovarian cancer and normal control patients and among patients with different stages and different grades, as well as between patients with lymph node metastasis and non–lymph node metastasis. We then investigated the value of the MLR in predicting the stage, grade, and lymph node positivity by using logistic regression. The impact of the MLR on overall survival (OS was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: Statistically significant differences in the MLR were observed between ovarian cancer patients and normal controls. However, no difference was found for the NLR and PLR. Highly significant differences in the MLR were found among patients with different stages (stage I-II and stage III-IV, grades (G1 and >G1, and lymph node metastasis status. The MLR was a significant and independent risk factor for lymph node metastasis, as determined by logistic regression. The optimal cutoff value of the MLR was 0.23. We also classified the data according to tumor markers (CA125, CA199, HE4, AFP, and CEA and conventional coagulation parameters (International Normalized Ratio [INR] and fibrinogen. Highly significant differences in CA125, CA199, HE4, INR, fibrinogen levels, and lactate

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

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

    2018-06-01

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

  20. Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME?

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    Dumler J Stephen

    2006-07-01

    Full Text Available Abstract Background Human monocytic ehrlichiosis (HME and Rocky Mountain spotted fever (RMSF are caused by Ehrlichia chaffeensis and Rickettsia rickettsii, respectively. The pathogenesis of RMSF relates to rickettsia-mediated vascular injury, but it is unclear in HME. Methods To study histopathologic responses in the lymphatic system for correlates of immune injury, lymph nodes from patients with HME (n = 6 and RMSF (n = 5 were examined. H&E-stained lymph node tissues were examined for five histopathologic features, including hemophagocytosis, cellularity, necrosis, and vascular congestion and edema. The relative proportions of CD68 macrophages, CD8 and CD4 T lymphocytes, and CD20 B lymphocytes were evaluated by immunohistochemical staining. Results Hemophagocytosis was similar in HME and RMSF, and was greater than in control cases (p = .015. Cellularity in HME was not different from controls, whereas RMSF lymph nodes were markedly less cellular (p E. chaffeensis-infected mononuclear phagocytes were infrequent compared to R. rickettsii-infected endothelial cells. More CD8 cells in lymph nodes were observed with HME (p Conclusion Hemophagocytosis, CD8 T cell expansion, and the paucity of infected cells in HME, suggest that E. chaffeensis infection leads to macrophage activation and immune-mediated injury.

  1. Respective roles and interactions of T-lymphocyte and PGE2-mediated monocyte suppressive activities in human newborns and mothers at the time of delivery

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    Durandy, A.; Fischer, A.; Mamas, S.; Dray, F.; Griscelli, C.

    1982-01-01

    Recently the concept of a poorly functional humoral immune response in the newborn was proposed. Data have been presented indicating that the impaired newborn B cell maturation, as shown in vitro in a pokeweed mitogen-induced B cell maturation system, is due both to an immaturity of lymphocyte subsets and to an increased suppressive T activity. In the present work, we present evidence that there exists a predominance of a naturally occurring T lymphocyte suppressive activity in the cord blood in that the removal of the suppressive activity by irradiation allows a normal maturation of newborn B cells. Such normal maturation of newborn B cells can also be obtained using mixed cultures of adult T cells and newborn B cells. Newborn suppressor T cells belong to both EA gamma (+) and EA gamma (-) fractions, and it is not known whether these two groups do or do not belong to different subsets. The PGE2-dependent monocyte suppressive activity does not play any role in the suppression observed in newborns since newborn monocytes are poorly suppressive and since they produce a smaller amount of PGE2 than adult monocytes. Some observations suggest, on the contrary, that the suppressive T lymphocytes can regulate the level of the PGE2-dependent monocyte suppressive activity. It should be noticed that similar observations about T lymphocyte and PGE2-dependent monocyte suppressive activities have been made at the same time using mothers' cells. These observations suggest the possibility that such changes in B cell immune regulation may result from an interaction between maternal and fetal lymphoid cells

  2. Impact of chronic and acute academic stress on lymphocyte subsets and monocyte function.

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    Viktoriya Maydych

    Full Text Available This study investigated the effects of a temporally confined naturalistic stressor (academic stress on immune functions. Furthermore, moderating influences of a number of psychological variables were assessed. Five blood samples were obtained from 20 students during an observation period of 8 weeks, starting 4.5 weeks before an exam period up to 1 week following the last exam. The analysis of 45 immune parameters revealed several time-dependent changes attributable to examination stress. We observed a reduction in the absolute numbers of natural killer (NK cells and monocytes in peripheral blood and a shift towards more immature and naïve cells within NK and T cell populations. In addition, IL-6 and TNF-α production by LPS-stimulated monocytes was increased. Psychological variables were grouped by means of factor analyses into two factors. One factor, which was interpreted as an indication of chronic stress, moderated the relationships between academic stress and percentages of mature CD57+ NK cells. This chronic stress factor was also associated with an increase in memory and a decrease in naïve CD8 T cells and increased serum levels of IL-17. The present study identifies important potential psychological mediators of stress-induced changes in specific immunological parameters.

  3. The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis.

    Science.gov (United States)

    Guo, Ya-Huan; Sun, Hai-Feng; Zhang, Yan-Bing; Liao, Zi-Jun; Zhao, Lei; Cui, Jie; Wu, Tao; Lu, Jian-Rong; Nan, Ke-Jun; Wang, Shu-Hong

    2017-03-21

    Conflicting evidence exists regarding the effects of platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio(LMR) on the prognosis of colorectal cancer (CRC) patients. This study aimed to evaluate the roles of the PLR and LMR in predicting the prognosis of CRC patients via meta-analysis. Eligible studies were retrieved from the PubMed, Embase,andChina National Knowledge Infrastructure (CNKI) databases, supplemented by a manual search of references from retrieved articles. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated using the generic inverse variance and random-effect model to evaluate the association of PLR and LMR with prognostic variables in CRC, including overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Thirty-three studies containing 15,404 patients met criteria for inclusion. Pooled analysis suggested that elevated PLR was associated with poorer OS (pooled HR = 1.57, 95% CI: 1.41 - 1.75, p< 0.00001, I2=26%) and DFS (pooled HR = 1.58, 95% CI: 1.31 - 1.92, p< 0.00001, I2=66%). Conversely, high LMR correlated with more favorable OS (pooled HR = 0.59, 95% CI: 0.50 - 0.68, p< 0.00001, I2=44%), CSS (pooled HR = 0.54, 95% CI: 0.40 - 0.72, p< 0.00001, I2=11%) and DFS (pooled HR = 0.82, 95% CI: 0.71- 0.94,p=0.005, I2=29%). Elevated PLR was associated with poor prognosis, while high LMR correlated with more favorable outcomes in CRC patients. Pretreatment PLR and LMR could serve as prognostic predictors in CRC patients.

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

    Directory of Open Access Journals (Sweden)

    Peng JH

    2017-07-01

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

  5. HIV-1 infection and first line ART induced differential responses in mitochondria from blood lymphocytes and monocytes: the ANRS EP45 "Aging" study.

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    Sophie Perrin

    Full Text Available The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence.49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999. In more than 88% of treated patients, the viral load was 500/mm(3. ROS (reactive oxygen species production and ΔΨm (inner membrane potential were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters. Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively were analysed by western blotting.Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm or morphological (network volume density, fragmentation and branching parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria.In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes, or from first line ART

  6. Eosinophilic infiltration in Korea: idiopathic?

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Hoon; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2006-03-15

    Eosinophilia is defined as the presence of more than 500 eosinophils/{mu}L in the peripheral blood, and may be accompanied by eosinophil infiltration in tissues. Focal eosinophilic infiltration in the lungs and liver is relatively common and is often associated with a parasitic infection, drug hypersensitivity, allergic diseases, collagen vascular diseased, and internal malignancies such as Hodgkin's disease, as well as cancer of the lung, stomach, pancreas or ovary. An eosinophilic abscess refers to a lesion of massive eosinophil infiltration and associated destroyed tissue, and an eosinophilic granuloma refers to a lesion consisting of central necrosis and mixed inflammatory cell infiltrates with numerous eosinophils, a number of neutrophils and lymphocytes, and a palisade of epithelioid histiocytes and/or giant cells.

  7. Eosinophilic infiltration in Korea: idiopathic?

    International Nuclear Information System (INIS)

    Lim, Jae Hoon; Lee, Kyung Soo

    2006-01-01

    Eosinophilia is defined as the presence of more than 500 eosinophils/μL in the peripheral blood, and may be accompanied by eosinophil infiltration in tissues. Focal eosinophilic infiltration in the lungs and liver is relatively common and is often associated with a parasitic infection, drug hypersensitivity, allergic diseases, collagen vascular diseased, and internal malignancies such as Hodgkin's disease, as well as cancer of the lung, stomach, pancreas or ovary. An eosinophilic abscess refers to a lesion of massive eosinophil infiltration and associated destroyed tissue, and an eosinophilic granuloma refers to a lesion consisting of central necrosis and mixed inflammatory cell infiltrates with numerous eosinophils, a number of neutrophils and lymphocytes, and a palisade of epithelioid histiocytes and/or giant cells

  8. Eosinophilic Fasciitis Associated with Myositis

    Directory of Open Access Journals (Sweden)

    Yuko Adachi

    2015-04-01

    Full Text Available Eosinophilic fasciitis is clinically characterized by symmetrical scleroderma-like indurations of the skin with pain. The histological features are fascial inflammation with lymphocytes and eosinophils as well as thickened and fibrotic fascia. Lymphocytic infiltration and degeneration of the underlying muscle are rarely observed. We report a 69-year-old Japanese woman who presented with multiple areas of glossy induration and painful peau d'orange-like lesions on the chest and four extremities. T2-weighted magnetic resonance imaging showed significant hyperintense thickening of the fascia of the lower extremities. Histopathological examination of a biopsy specimen from the induration showed marked fibrinoid degeneration of the fascia and the neighboring muscle with mixed cellular infiltration of lymphocytes and eosinophils. The predominant CD8+ lymphocytic infiltrates were observed by immunohistological study. A diagnosis of eosinophilic fasciitis with myositis was made. Oral administration of prednisolone and discontinuation of exercise significantly improved the lesions and pain.

  9. Monocytes can be induced by lipopolysaccharide-triggered T lymphocytes to express functional factor VII/VIIa protease activity

    OpenAIRE

    1984-01-01

    In the present study we demonstrate that human monocytes can be induced by the model stimulus, lipopolysaccharide (LPS), to produce and assemble on their surface functional Factor VII/VIIa. This protease was not induced in relatively purified monocytes alone following exposure to LPS; but was induced in the presence of Leu-3a positive helper/inducer T cells. The Factor VII/VIIa protease activity represented 35-40% of the potential initiating activity for the extrinsic coagulation pathway and ...

  10. A large cohort study reveals the association of elevated peripheral blood lymphocyte-to-monocyte ratio with favorable prognosis in nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available BACKGROUND: Nasopharyngeal carcinoma (NPC is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20-30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients. METHODS: A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS, disease-free survival (DFS, distant metastasis-free survival (DMFS and loco-regional recurrence-free survival (LRRFS, respectively. RESULTS: Univariate analysis revealed that higher LMR level (≥ 5.220 was significantly associated with superior OS, DFS and DMFS (P values <0.001. The higher lymphocyte count (≥ 2.145 × 10(9/L was significantly associated with better OS (P = 0.002 and DMFS (P = 0.031, respectively, while the lower monocyte count (<0.475 × 10(9/L was associated with better OS (P = 0.012, DFS (P = 0.011 and DMFS (P = 0.003, respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.558, 95% confidence interval or 95% CI = 0.417-0.748; P<0.001, DFS (HR = 0.669, 95% CI = 0.535-0.838; P<0.001 and DMFS (HR = 0.543, 95% CI = 0.403-0.732; P<0.001, respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053 and DMFS (P = 0.080. CONCLUSIONS: The

  11. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Torpey, D.J. III

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with /sup 51/Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant.

  12. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Torpey, D.J. III.

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with 51 Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant

  13. The effect of cytosolic extract of Alternaria aternata fungus on Monocyte-derived dendritic cell maturation and T-lymphocyte polarization in the presence of myelin basic protein

    Directory of Open Access Journals (Sweden)

    Loghmanni A

    2013-03-01

    Full Text Available Background: Multiple Sclerosis (MS is an autoimmune disease with impairment in function of central nervous system. Macrophages and dendritic cells play important roles in alleviating or progression of the disease. These cells can cause inflammation and damage to the myelin of nerve cells by realizing of harmful substances when these cells get matured. We studied the effect of Alternaria alternata extract on maturation of monocyte- derived dendritic cell (modc and T-cell responses in the presence of Myelin Basic Protein (MBP as a laboratory model of multiple sclerosis (MS. The purpose of this study is suitable dendritic cells production for usage in MS immunotherapy.Methods: For this study plastic adherent monocytes were cultured with granulocyte/ macrophage- colony stimulating factor (GM-CSF and interleukin -4 for converting these cells to modc and pulsed with MBP and matured in the presence of monocyte-conditioned medium (MCM in control group and MCM + Alternaria alternata extract in treatment groups. Anti-CD14, anti-CD83, anti-human leukocyte antigen-DR (anti HLA-DR monoclonal antibody were carried out for phenotyping. Autologos T cell responses and cytokine production were evaluated.Results: The results showed that the expression of CD14 decreased and CD83, HLA-DR increased in treatment groups in comparison with control groups. The production amount of IL-10 overcame IL-12 and in T cell the production of cytokines, IL-17 and Interferon-γ (IFN-γ decreased and IL-4 was increased (P<0.05. These effects escalated with increasing of dosage from 50 to 100 (mg/ml (P<0.001.Conclusion: Alternaria alternata extract can cause maturation of MBP-pulsed modc and skewing of T- lymphocyte toward Th2 and thereby can evolve into a new strategy in immunotherapy of MS.

  14. Cisplatin-Induced Eosinophilic Pneumonia

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    Hideharu Ideguchi

    2014-01-01

    Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

  15. Leukemia -- Eosinophilic

    Science.gov (United States)

    ... social workers, and patient advocates. Cancer.Net Guide Leukemia - Eosinophilic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

  16. Eosinophilic oesophagitis

    DEFF Research Database (Denmark)

    Nielsen, Rasmus Gaardskjær; Husby, Steffen

    2007-01-01

    Eosinophilic oesophagitis is characterised by age-dependent symptoms mimicking gastrooesophageal reflux disease, a distinct endoscopic appearance and a histological picture with extensive infiltration of eosinophils in the oesophageal mucosa. Eosinophilic oesophagitis is more frequently seen...... in males, and patients often belong to the paediatric or adolescence age groups. The exact prevalence of eosinophilic oesophagitis is unknown, but it has been suggested that the United States has a higher prevalence than Europe. Several treatment algorithms have been suggested, including elemental diets......, oral steroids, inhaled (swallowed) steroids, and leucotriene receptor antagonists. Detailed information on the eosinophilic inflammatory processes in the oesophageal mucosa was initially obtained from animal models, in particular with regard to the role of interleukin-5 and the chemokine eotaxin-1...

  17. Eosinophilic Dermatosis of Hematologic Malignancy.

    Science.gov (United States)

    Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

    Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Eosinophilic esophagitis

    Science.gov (United States)

    ... of the American Academy of Allergy, Asthma and Immunology. Dietary therapy and nutrition management of eosinophilic esophagitis: ... of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol Pract . 2017;5(2): ...

  19. Eosinophilic panniculitis.

    Science.gov (United States)

    Samlaska, C P; de Lorimier, A J; Heldman, L S

    1995-03-01

    Eosinophillic panniculitis is a poorly defined entity with variable clinical features. We report a case of rapidly enlarging, asymptomatic subcutaneous scalp nodules in a 6-year-old black boy with atopic dermatitis. The nodules resolved spontaneously over two to three days. Biopsy specimens were remarkable for eosinophilic panniculitis without evidence of epidermal change or vasculitis. We believe that this is the youngest reported patient with this disorder.

  20. Properties of human blood monocytes. I. CD91 expression and log orthogonal light scatter provide a robust method to identify monocytes that is more accurate than CD14 expression.

    Science.gov (United States)

    Hudig, Dorothy; Hunter, Kenneth W; Diamond, W John; Redelman, Doug

    2014-03-01

    This study was designed to improve identification of human blood monocytes by using antibodies to molecules that occur consistently on all stages of monocyte development and differentiation. We examined blood samples from 200 healthy adults without clinically diagnosed immunological abnormalities by flow cytometry (FCM) with multiple combinations of antibodies and with a hematology analyzer (Beckman LH750). CD91 (α2 -macroglobulin receptor) was expressed only by monocytes and to a consistent level among subjects [mean median fluorescence intensity (MFI) = 16.2 ± 3.2]. Notably, only 85.7 ± 5.82% of the CD91(+) monocytes expressed high levels of the classical monocyte marker CD14, with some CD91(+) CD16(+) cells having negligible CD14, indicating that substantial FCM under-counts will occur when monocytes are identified by high CD14. CD33 (receptor for sialyl conjugates) was co-expressed with CD91 on monocytes but CD33 expression varied by nearly ten-fold among subjects (mean MFI = 17.4 ± 7.7). In comparison to FCM analyses, the hematology analyzer systematically over-counted monocytes and eosinophils while lymphocyte and neutrophil differential values generally agreed with FCM methods. CD91 is a better marker to identify monocytes than CD14 or CD33. Furthermore, FCM (with anti-CD91) identifies monocytes better than a currently used clinical CBC instrument. Use of anti-CD91 together with anti-CD14 and anti-CD16 supports the identification of the diagnostically significant monocyte populations with variable expression of CD14 and CD16. Copyright © 2013 Clinical Cytometry Society.

  1. Day 100 Peripheral Blood Absolute Lymphocyte/Monocyte Ratio and Survival in Classical Hodgkin's Lymphoma Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Luis F. Porrata

    2013-01-01

    Full Text Available Day 100 prognostic factors of postautologous peripheral blood hematopoietic stem cell transplantation (APBHSCT to predict clinical outcome in classical Hodgkin lymphoma (cHL patients have not been evaluated. Thus, we studied if the day 100 peripheral blood absolute lymphocyte/monocyte ratio (Day 100 ALC/AMC affects clinical outcomes by landmark analysis from day 100 post-APBHSCT. Only cHL patients achieving a complete remission at day 100 post-APBHSCT were studied. From 2000 to 2010, 131 cHL consecutive patients qualified for the study. The median followup from day 100 was 4.1 years (range: 0.2–12.3 years. Patients with a Day 100 ALC/AMC ≥ 1.3 experienced superior overall survival (OS and progression-free survival (PFS compared with Day 100 ALC/AMC < 1.3 (from day 100: OS, median not reached versus 2.8 years; 5 years OS rates of 93% (95% CI, 83%–97% versus 35% (95% CI, 19%–51%, resp., P<0.0001; from day 100: PFS, median not reached versus 1.2 years; 5 years PFS rates of 79% (95% CI, 69%–86% versus 27% (95% CI, 14%–45%, resp., P<0.0001. Day ALC/AMC ratio was an independent predictor for OS and PFS. Thus, Day 100 ALC/AMC ratio is a simple biomarker that can help to assess clinical outcomes from day 100 post-APBHSCT in cHL patients.

  2. Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.

    Science.gov (United States)

    Lingblom, Christine; Andersson, Jennie; Andersson, Kerstin; Wennerås, Christine

    2017-06-15

    Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16 hi subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16 hi eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Eosinophilic cystitis

    DEFF Research Database (Denmark)

    Mosholt, Karina Sif Søndergaard; Dahl, Claus; Azawi, Nessn Htum

    2014-01-01

    Eosinophilic cystitis (EC) is a rare disease. We describe three cases, where presentations of the disease are similar. To highlight probable causes of the disease, symptoms, clinical findings and treatment modalities, we reviewed 56 cases over a 10-year period. The most common symptoms were...

  4. Leukotactin-1/CCL15 induces cell migration and differentiation of human eosinophilic leukemia EoL-1 cells through PKCdelta activation.

    Science.gov (United States)

    Lee, Ji-Sook; Kim, In Sik

    2010-06-01

    Leukotactin-1 (Lkn-1)/CCL15 is a CC chemokine that binds to the CCR1 and CCR3. Lkn-1 functions as an essential factor in the migration of monocytes, lymphocytes, and neutrophils. Although eosinophils express both receptors, the role of Lkn-1 in immature eosinophils remains to be elucidated. In this present study, we investigated the contribution of the CCR1-binding chemokines to chemotactic activity and in the differentiation in the human eosinophilic leukemia cell line EoL-1. Lkn-1 induced the stronger migration of EoL-1 cells than other CCR1-binding chemokines such as RANTES/CCL5, MIP-1alpha/CCL3 and HCC-4/CCL16. Lkn-1-induced chemotaxis was inhibited by pertussis toxin, an inhibitor of G(i)/G(o) protein; U73122, an inhibitor of phospholipase C and rottlerin, an inhibitor of protein kinase C delta (PKCdelta). Lkn-1 increased PKCdelta activity, which was partially blocked by the pertussis toxin and U73122. Lkn-1 enhanced the butyric acid-induced differentiation via PKCdelta after binding to the increased CCR1 because Lkn-1 caused EoL-1 cells to change morphologically into mature eosinophil-like cells. Likewise, Lkn-1 increased the expression of both eosinophil peroxidase (EPO) and the major basic protein (MBP). PKCdelta activation due to Lkn-1 is involved in migration, as well as the butyric acid-induced differentiation. This finding contributes to an understanding of CC chemokines in eosinophil biology and to the development of novel therapies for the treatment of eosinophilic disorders. This study suggests the pivotal roles of Lkn-1 in the regulation of the movement and development of eosinophils.

  5. Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.

    Science.gov (United States)

    Lingblom, C; Wallander, J; Ingelsten, M; Bergquist, H; Bove, M; Saalman, R; Welin, A; Wennerås, C

    2017-03-01

    Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (T regs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of T regs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in T regs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE. © 2016 British Society for Immunology.

  6. Eosinophilic fasciitis

    Directory of Open Access Journals (Sweden)

    Karolina Niklas

    2015-01-01

    Full Text Available Eosinophilic fasciitis is a rare connective tissue disease with unclear etiology and pathogenesis. It is classified as a scleroderma-like syndrome. The disease is characterized by fibrosis of the skin and subcutaneous tissues with significant thickening of fascia. Visceral involvement is rare. Characteristic feature in laboratory tests is peripheral blood eosinophilia. Differential diagnosis should be performed, including ruling out systemic sclerosis, nephrogenic systemic fibrosis, eosinophilia-myalgia syndrome, scleromyxedema, hypereosinophilic syndrome or Churg-Strauss syndrome. Final diagnosis is confirmed by histopathological examination. In treatment of the disease corticosteroids and/or immunosuppressive drugs are used. Some other drugs showed activity in this disease e.g. dapsone, infiximab or rituximab. Prognosis is rather good but sometimes a long-term treatment is necessary. In this paper we summarized the current knowledge on eosinophilic fasciitis.

  7. CXCR3 expression and activation of eosinophils

    DEFF Research Database (Denmark)

    Jinquan, T; Jing, C; Jacobi, H H

    2000-01-01

    CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. gamma IP-10 and Mig induce...... in eosinophils are up- and down-regulated by IL-2 and IL-10, respectively, as detected using flow cytometry, immunocytochemical assay, and a real-time quantitative RT-PCR technique. gamma IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact...

  8. Eosinophilic ascites due to severe eosinophilic ileitis

    Directory of Open Access Journals (Sweden)

    Setia Namrata

    2010-01-01

    Full Text Available Background: There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. Case Presentation: A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Conclusion: Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis.

  9. Eosinophilic ascites due to severe eosinophilic ileitis.

    Science.gov (United States)

    Setia, Namrata; Ghobrial, Peter; Liron, Pantanowitz

    2010-09-17

    There is a broad etiology for effusion eosinophilia that includes allergic, reactive, infectious, immune, neoplastic, and idiopathic causes. We report and describe the cytomorphologic findings of a rare case of eosinophilic ascites due to severe eosinophilic ileitis. A 17-year-old male manifested acutely with eosinophilic ascites due to severe biopsy-proven subserosal eosinophilic ileitis. Isolated peritoneal fluid submitted for cytologic evaluation revealed that 65% eosinophils were present in a bloody background. The patient responded to corticosteroids, with complete resolution of his ascites. Eosinophilic gastroenteritis with subserosal involvement should be added to the list of causes for eosinophils in peritoneal fluid. The finding of eosinophilic ascites, with appropriate clinical and laboratory findings, may warrant the need to perform laparoscopic intestinal biopsies to confirm the diagnosis.

  10. Protective Role of Eosinophils and TNFa after Ozone Inhalation.

    Science.gov (United States)

    Fryer, Allison D; Jacoby, David B; Wicher, Sarah A

    2017-03-01

    bronchoconstriction compared with allergic animals not treated with etanercept. Etanercept tended to increase the numbers of blood monocytes and lymphocytes in air- and ozone-exposed normal and allergic animals at day 3, but had no effect on eosinophils in blood at this time point. This was one of the few statistically significant findings in the blood of exposed animals in the study. 3. Anti-IL-5 reduced bronchoconstriction at day 3 after exposure of allergic animals to ozone. In contrast, bronchoconstriction was greatly increased in normal animals treated with anti-IL-5. Fryer and colleagues explored the airway and cellular responses in guinea pigs exposed to ozone. The HEI Review Committee, which conducted an independent review of the study, agreed that the findings supported the authors’ hypothesis (1) that exposure to ozone stimulates production of eosinophils in bone marrow, (2) that these newly formed eosinophils migrate to the lungs, and (3) that those eosinophils play a delayed but potentially beneficial role in reducing ozone-induced inflammation in the airways of healthy normal animals, but not in allergen-sensitized animals. The Committee also agreed that guinea pigs were a good model for studying responses to an allergen, because a major subtype of asthma (the high Th2 or allergic type) is associated with high levels of eosinophils in the blood. A novel finding was that the TNFa blocker etanercept decreased ozone-induced formation of eosinophils in the bone marrow and blocked eosinophil migration to the lung in normal animals. However, because injecting etanercept had little effect on eosinophils and did not decrease bronchoconstriction in allergic guinea pigs, the potential for treating patients with allergic asthma with TNFa blockers is uncertain. This is consistent with the poor performance of TNFa blockers in clinical studies of asthma treatment. Blocking the cytokine IL-5 with an anti-IL-5 antibody substantially decreased bronchoconstriction in sensitized animals

  11. Monocytic leukemias.

    Science.gov (United States)

    Shaw, M T

    1980-05-01

    The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

  12. Scleroderma mimicker – Eosinophilic fasciitis

    Directory of Open Access Journals (Sweden)

    Debanjali Sinha

    2017-01-01

    Full Text Available Eosinophilic fasciitis is an uncommon connective tissue disorder characterized by thickening of the deep fascia and overlying skin and subcutaneous tissue. It may mimic scleroderma and other scleroderma-like conditions. It may be a manifestation of paraneoplastic disorders or may be associated with hematological disorders including lymphomas. Definitive diagnosis is made on histological examination of a deep skin biopsy revealing thickened deep fascia and infiltration by lymphocytes and eosinophils. Enhancement of deep fascia on Gadolinium contrast-enhanced magnetic resonance imaging may be used as a substitute for skin biopsy. Ultrasound imaging is an evolving imaging tool for diagnosing it. Glucocorticoids with or without immunosuppressive agents remains the mainstay of therapy with good response, generally. A younger age of onset, morphea like lesions and dermal fibrosclerosis is more likely to be associated with the refractory disease. Early diagnosis and appropriate treatment may result in better outcomes in terms of morbidity and quality of life of the patients.

  13. Eosinophilic Lung Disorders

    Science.gov (United States)

    ... problems characterized by having an increased number of eosinophils (white blood cells) in the lungs. These white ... category of pneumonias that feature increased numbers of eosinophils in the lung tissue. Pneumonia is an inflammatory ...

  14. Preparation and surface labeling of murine eosinophils

    International Nuclear Information System (INIS)

    Burgess, A.W.; Cruise, K.M.; Mitchell, G.F.; Watt, S.M.

    1980-01-01

    Eosinophilic polymorphonuclear leukocytes were isolated from the peritoneal cavity of BALB/c mice infected with the parasite Mesocestoides corti. Approximately 4 x 10 7 eosinophils (purity, 50%) could be harvested from each mouse. A high yield and purity of eosinophils was obtained from the peritoneal cells of infected male BALB/c mice using density centrifugation on a gradient of slightly hypotonic colloidal silica sol (Percoll). After initial irradiation of the mice to lower the lymphocyte contamination, subsequent density gradient (and where nescessary sedimentation velocity) centrifugation yielded 10 8 eosinophils (purity >95%) from six to eight mice. It was also possible to isolate small numbers of eosinophils (2 x 10 4 cells/minute, purity >99%) without irradiating the mice. This could be achieved by separating the density gradient purified peritoneal cells by light-scatter on a Becton-Dickinson cell sorter (FACS II). Analysis of proteins extracted from eosinophils using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed a group of high molecular weight proteins (between 250K and 160K) which were not as distinctive in the neutrophil profile. Surface labeling was performed, before the cell separation, by using 125 I and 1,3,4,6-tetrachloro-3α,6α-diphenylglycoluril. Only five 125 I-labeled proteins were detected initially (all with apparent molecular weights >50,000). No 125 I appeared to be associated with actin under the conditions used for surface labeling. Four of the eosinophil surface labeled proteins corresponded to surface labeled proteins on neutrophils, but the major surface component of the eosinophils (MW 79,000) appeared to be smaller than the major neutrophil protein (MW 90,000). (author)

  15. Eosinophilic Endotype of Asthma.

    Science.gov (United States)

    Aleman, Fernando; Lim, Hui Fang; Nair, Parameswaran

    2016-08-01

    Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Eosinophilic cystitis in children

    International Nuclear Information System (INIS)

    Liu Ming; Zhang Yuzhen; Li Yuhua; Wang Qiuyan; Xie Hua

    2006-01-01

    Objective: To discuss the clinical manifestations and CT findings of eosinophilic cystitis in children. Methods: Nine cases including Six boys and 3 girls, three to 13 years old, mean age of 8.3- year, have symptoms of hematuria, irritative voiding, dysuria and abdominal pain. The eosinophilic cystitis was pathologically proved in 7 patients and eosinophilic granulomatous cystitis in 2 patients, which based on cystoscopic tissue biopsy or surgery retrospectively. Results: Local thickened bladder walls or nodular and sessile masses along the bladder dome showed in four cases with eosinophilic granulomatous cystitis, and the diffusely irregularly thickened bladder wails showed on CT scans in the rest 5 cases with eosinophilic cystitis. Conclusion: CT findings are helpful to reveal the site, size and other features of eosinophilic cystitis in children. But biopsy of the lesion is necessary to rule out other bladder tumor and selecting the proper management. (authors)

  17. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková

    2017-04-01

    Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  18. Proteomics of Eosinophil Activation

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    Deane F. Mosher

    2017-09-01

    Full Text Available We recently identified and quantified >7,000 proteins in non-activated human peripheral blood eosinophils using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS and described phosphoproteomic changes that accompany acute activation of eosinophils by interleukin-5 (IL5 (1. These data comprise a treasure trove of information about eosinophils. We illustrate the power of label-free LC–MS/MS quantification by considering four examples: complexity of eosinophil STATs, contribution of immunoproteasome subunits to eosinophil proteasomes, complement of integrin subunits, and contribution of platelet proteins originating from platelet–eosinophil complexes to the overall proteome. We describe how isobaric labeling enables robust sample-to-sample comparisons and relate the 220 phosphosites that changed significantly upon treatment with IL5 to previous studies of eosinophil activation. Finally, we review previous attempts to leverage the power of mass spectrometry to discern differences between eosinophils of healthy subjects and those with eosinophil-associated conditions and point out features of label-free quantification and isobaric labeling that are important in planning future mass spectrometric studies.

  19. Eosinophils in Autoimmune Diseases

    Science.gov (United States)

    Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

    2017-01-01

    Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

  20. A key requirement for CD300f in innate immune responses of eosinophils in colitis.

    Science.gov (United States)

    Moshkovits, I; Reichman, H; Karo-Atar, D; Rozenberg, P; Zigmond, E; Haberman, Y; Ben Baruch-Morgenstern, N; Lampinen, M; Carlson, M; Itan, M; Denson, L A; Varol, C; Munitz, A

    2017-01-01

    Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. We have recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f -/- mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f -/- mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.

  1. The effect of beta-hydroxy-beta-methylbutyrate (HMB) on the proliferative response of blood lymphocytes and the phagocytic activity of blood monocytes and granulocytes in calves.

    Science.gov (United States)

    Wójcik, R; Małaczewska, J; Siwicki, A K; Miciński, J; Zwierzchowski, G

    2013-01-01

    The objective of this study was to evaluate the effect of HMB on selected indicators of immunity in calves. The experiment was performed on 14 calves aged 30 +/- 2 days, divided into two equal groups of control (group I) and experimental (group II) animals. The feed administered to experimental group calves was supplemented with HMB at 40 mg/kg BW, whereas control calves were administered standard farm-made feed without supplementation. Blood was sampled from the jugular vein immediately before the experiment (day 0) and on experimental days 15, 30 and 60 to determine the following parameters of immunity: proliferative response of LPS- and ConA-stimulated lymphocytes (MTT), respiratory burst activity (RBA) and potential killing activity (PKA) of phagocytes. The results revealed a significant increase in RBA and MTT values in calves administered HMB in comparison with the control group throughout the experiment. In the group of animals receiving HMB, an increase in PKA values was noted only on day 30.

  2. Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

    Directory of Open Access Journals (Sweden)

    Yu-Mu Chen

    Full Text Available Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC receiving first-line epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKIs has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS and overall survival (OS in EGFR-mutant patients with NSCLC.Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR, determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR.The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001, whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001.A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

  3. CD16+ monocytes and skewed macrophage polarization toward M2 type hallmark heart transplant acute cellular rejection

    NARCIS (Netherlands)

    T.P.P. van den Bosch (Thierry); K. Caliskan (Kadir); M.D. Kraaij (Marina); A.A. Constantinescu (Alina); O.C. Manintveld (Olivier); P.J. Leenen (Pieter); J. von der Thusen (Jan); M.C. Clahsen-van Groningen (Marian); C.C. Baan (Carla); A.T. Rowshani (Ajda)

    2017-01-01

    textabstractBackground: During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during

  4. 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.

  5. Eosinophilic Esophagitis (EoE)

    Science.gov (United States)

    ... specific responses in allergy? » Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis: A Work Group Report of the American Academy of Allergy, Asthma, and Immunology » Eosinophilic esophagitis can ...

  6. Sinusitis with eosinophilic otitis media

    International Nuclear Information System (INIS)

    Kawano, Toshiro; Ishitoya, Junichi; Tsukuda, Mamoru

    2007-01-01

    Eosinophilic otitis media is an intractable inflammation of the middle ear combined with bronchial asthma. According to a national epidemiological investigation on eosinophilic otitis media, it is assumed that eosinophilic otitis media are combined with sinusitis in about 74% of their cases. On the other hand, organizational images of eosinophilic otitis media and eosinophilic sinusitis are similar, and steroid therapy is effective together, and it is thought that they are involved in the idea of one airway one disease, but the details of sinusitis combined with the eosinophilic otitis media are unidentified. Therefore, we examined the kinds of the sinusitis combined with eosinophilic otitis media. We diagnosed 18 cases (male: 2 cases, female: 16 cases) (average age: 54.6 years old) as eosinophilic otitis media according to the diagnostic criteria. And, by the CT views of a paranasal sinus, blood tests, existence of the nasal polyp, etc, we investigated the kinds of sinusitis combined with eosinophilic otitis media. It turned out that bronchial asthma was combined with eosinophilic otitis media in 17 of 18 cases (airway hypersensitivity did sthenia of one case, but the asthma did not yet developed), and 6 cases were combined with aspirin induced asthma (AIA), and 3 cases were combined with Churg-Strauss syndromes (CSS). 10 case (55.6%) of 17 eosinophilic otitis media were combined with eosinophilic sinusitis. And 4 cases (22.2%) of 17 eosinophilic otitis media were combined with chronic sinusitis, 4 cases (22.2%) of 17 eosinophilic otitis media were not combined with sinusitis. We concluded that eosinophilic otitis media was not always combined with eosinophilic sinusitis. The idea of one airway one disease was not applied to this examination. (author)

  7. Sinusitis with eosinophilic otitis media

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Toshiro; Ishitoya, Junichi [Yokohama City Univ., Medical Center, Yokohama, Kanagawa (Japan); Tsukuda, Mamoru [Yokohama City Univ., Graduate School of Medicine, Yokohama, Kanagawa (Japan)

    2007-09-15

    Eosinophilic otitis media is an intractable inflammation of the middle ear combined with bronchial asthma. According to a national epidemiological investigation on eosinophilic otitis media, it is assumed that eosinophilic otitis media are combined with sinusitis in about 74% of their cases. On the other hand, organizational images of eosinophilic otitis media and eosinophilic sinusitis are similar, and steroid therapy is effective together, and it is thought that they are involved in the idea of one airway one disease, but the details of sinusitis combined with the eosinophilic otitis media are unidentified. Therefore, we examined the kinds of the sinusitis combined with eosinophilic otitis media. We diagnosed 18 cases (male: 2 cases, female: 16 cases) (average age: 54.6 years old) as eosinophilic otitis media according to the diagnostic criteria. And, by the CT views of a paranasal sinus, blood tests, existence of the nasal polyp, etc, we investigated the kinds of sinusitis combined with eosinophilic otitis media. It turned out that bronchial asthma was combined with eosinophilic otitis media in 17 of 18 cases (airway hypersensitivity did sthenia of one case, but the asthma did not yet developed), and 6 cases were combined with aspirin induced asthma (AIA), and 3 cases were combined with Churg-Strauss syndromes (CSS). 10 case (55.6%) of 17 eosinophilic otitis media were combined with eosinophilic sinusitis. And 4 cases (22.2%) of 17 eosinophilic otitis media were combined with chronic sinusitis, 4 cases (22.2%) of 17 eosinophilic otitis media were not combined with sinusitis. We concluded that eosinophilic otitis media was not always combined with eosinophilic sinusitis. The idea of one airway one disease was not applied to this examination. (author)

  8. T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

    International Nuclear Information System (INIS)

    Han, T.; Dadey, B.

    1978-01-01

    Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

  9. Exosomes from eosinophils autoregulate and promote eosinophil functions.

    Science.gov (United States)

    Cañas, José Antonio; Sastre, Beatriz; Mazzeo, Carla; Fernández-Nieto, Mar; Rodrigo-Muñoz, José Manuel; González-Guerra, Andrés; Izquierdo, Manuel; Barranco, Pilar; Quirce, Santiago; Sastre, Joaquín; Del Pozo, Victoria

    2017-05-01

    Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma ( n = 58) and healthy volunteers ( n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma. © Society for Leukocyte Biology.

  10. Eosinophilic colitis in infants.

    Science.gov (United States)

    Lozinsky, Adriana Chebar; Morais, Mauro Batista de

    2014-01-01

    To review the literature for clinical data on infants with allergic or eosinophilic colitis. MEDLINE search of all indexes was performed using the words "colitis or proctocolitis and eosinophilic" or "colitis or proctocolitis and allergic" between 1966 and February of 2013. All articles that described patients' characteristics were selected. A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263) of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 per high-power field) in 89.3% (236/264) of patients. Most patients showed improvement with the removal of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients). Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow's milk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  11. Eosinophilic colitis in infants

    Directory of Open Access Journals (Sweden)

    Adriana Chebar Lozinsky

    2014-01-01

    Full Text Available OBJECTIVE: To review the literature for clinical data on infants with allergic or eosinophilic colitis. DATA SOURCE: MEDLINE search of all indexes was performed using the words ''colitis or procto-colitis and eosinophilic'' or ''colitis or proctocolitis and allergic'' between 1966 and February of 2013. All articles that described patients' characteristics were selected. DATA SYNTHESIS: A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263 of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 perhigh-power field in 89.3% (236/264 of patients. Most patients showed improvement with theremoval of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients. CONCLUSIONS: Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow'smilk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure.

  12. Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils.

    Science.gov (United States)

    Stubbs, Victoria E L; Schratl, Petra; Hartnell, Adele; Williams, Timothy J; Peskar, Bernhard A; Heinemann, Akos; Sabroe, Ian

    2002-07-19

    We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a potent and selective inducer of eosinophil and basophil shape change. In eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory burst, and L-selectin shedding but did not cause up-regulation of CD63 expression. Pretreatment of eosinophils with indomethacin also enhanced subsequent eosinophil shape change induced by eotaxin, although treatment with higher concentrations of indomethacin resulted in a decrease in the expression of the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell selectivity closely resembled those of prostaglandin D(2) (PGD(2)). Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD(2)-induced shape change responses were not. Treatment of eosinophils with specific inhibitors of phospholipase C (U-73122), phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein kinase (SB-202190) revealed roles for these pathways in indomethacin signaling. Indomethacin and its analogues may therefore provide a structural basis from which selective PGD(2) receptor small molecule antagonists may be designed and which may have utility in the treatment of allergic inflammatory disease.

  13. HIV-1 Latency in Monocytes/Macrophages

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Denise Silveira-Lemos

    2013-01-01

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

  16. Genetics of eosinophilic esophagitis.

    Science.gov (United States)

    Kottyan, L C; Rothenberg, M E

    2017-05-01

    Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.

  17. Genetics of Eosinophilic Esophagitis

    Science.gov (United States)

    2012-03-01

    disease of the esophagus that affects at least 4 in 10,000 persons.1 Although symptomatically resembling gastroe - sophageal reflux disease, EE is...clinically defined as esophageal eosinophilia (>_15 intraepithelial eosinophils per high-powered field) in the absence of abnormal acid reflux disease...that distinguish eosin- ophilic esophagitis (EoE) from other inflammatory disorders, including gastroesophageal reflux disease (GERD). As the prev

  18. Eosinophils in biopsy specimens of lichen sclerosus: a not uncommon finding.

    Science.gov (United States)

    Lester, Elizabeth B; Swick, Brian L

    2015-01-01

    Evolving lesions of lichen sclerosus (LS) pose a diagnostic challenge owing to an absence of classic findings of epidermal atrophy, dermal sclerosis, a band-like lymphocytic infiltrate and the presence of eosinophils. Retrospective specimens of LS were reviewed. Demographic information, biopsy vs. excision and the following histopathological characteristics were noted: presence and number of eosinophils, epidermal hyperplasia, spongiosis, early/transitional LS, well-developed LS and coexisting squamous cell carcinoma (SCC). Linear regression analysis was performed. The data consisted of 66 biopsies (36 male [M], 30 female [F]), from 53 individuals (33M, 20F), including 57 genital and 9 extragenital biopsies. Seven biopsies showed SCC, 28 showed epidermal hyperplasia and 14 exhibited spongiosis. Thirty-five specimens were early/transitional LS and commonly exhibited epidermal hyperplasia (57%), epidermotropism of lymphocytes (97%) and basement membrane thickening (97%). Thirty-five biopsies (53%) contained eosinophils (23 early/transitional lesions). Male gender (p = 0.074) was associated with increased eosinophils. The presence of SCC (p = 0.014) was a significant predictors of eosinophil number. Epidermal hyperplasia, epidermotropism of lymphocytes and basement membrane thickening are helpful features in identifying early LS. Eosinophils are not an uncommon finding in LS and are most common in male genital lesions and in LS associated with SCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

    DEFF Research Database (Denmark)

    Schratl, Petra; Royer, Julia F; Kostenis, Evi

    2007-01-01

    of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid......Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role...

  20. The Regulatory Function of Eosinophils.

    Science.gov (United States)

    Wen, Ting; Rothenberg, Marc E

    2016-10-01

    Eosinophils are a minority circulating granulocyte classically viewed as being involved in host defense against parasites and promoting allergic reactions. However, a series of new regulatory functions for these cells have been identified in the past decade. During homeostasis, eosinophils develop in the bone marrow and migrate from the blood into target tissues following an eotaxin gradient, with interleukin-5 being a key cytokine for eosinophil proliferation, survival, and priming. In multiple target tissues, eosinophils actively regulate a variety of immune functions through their vast arsenal of granule products and cytokines, as well as direct cellular interaction with cells in proximity. The immunologic regulation of eosinophils extends from innate immunity to adaptive immunity and also involves non-immune cells. Herein, we summarize recent findings regarding novel roles of murine and human eosinophils, focusing on interactions with other hematopoietic cells. We also review new experimental tools available and remaining questions to uncover a greater understanding of this enigmatic cell.

  1. Eosinophilic myositis: an updated review.

    Science.gov (United States)

    Selva-O'Callaghan, A; Trallero-Araguás, E; Grau, J M

    2014-01-01

    Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Re-defining the Unique Roles for Eosinophils in Allergic Respiratory Inflammation

    Science.gov (United States)

    Jacobsen, Elizabeth A.; Lee, Nancy A.; Lee, James J.

    2014-01-01

    Summary The role of eosinophils in the progression and resolution of allergic respiratory inflammation is poorly defined despite the commonality of their presence and in some cases their use as a biomarker for disease severity and/or symptom control. However, this ambiguity belies the wealth of insights that have recently been gained through the use of eosinophil-deficient/attenuated strains of mice that have demonstrated novel immunoregulatory and remodeling/repair functions for these cells in the lung following allergen provocation. Specifically, studies of eosinophil-deficient mice suggest that eosinophils contribute to events occurring in the lungs following allergen provocation at several key moments: (i) The initiating phase of events leading to Th2-polarized pulmonary inflammation, (ii) The suppression Th1/Th17 pathways in lung draining lymph nodes, (iii) The recruitment of effector Th2 T cells to the lung, and finally (iv) Mechanisms of inflammatory resolution that re-establish pulmonary homeostasis. These suggested functions have recently been confirmed and expanded upon using allergen provocation of an inducible eosinophil-deficient strain of mice (iPHIL) that demonstrated an eosinophil-dependent mechanism(s) leading to Th2 dominated immune responses in the presence of eosinophils in contrast to neutrophilic as well as mixed Th1/Th17/Th2 variant phenotypes in the absence of eosinophils. These findings highlighted that eosinophils are not exclusively downstream mediators controlled by T cells, dendritic cells (DC), and/or innate lymphocytic cells (ILC2). Instead, eosinophils appear to be more aptly described as significant contributors in complex interrelated pathways that lead to pulmonary inflammation and subsequently promote resolution and the re-establishment of homeostatic baseline. In this review we summarize and put into the context the evolving hypotheses that are now expanding our understanding of the roles eosinophils likely have in the lung

  3. Oxidative Mechanisms of Monocyte-Mediated Cytotoxicity

    Science.gov (United States)

    Weiss, Stephen J.; Lobuglio, Albert F.; Kessler, Howard B.

    1980-01-01

    Human monocytes stimulated with phorbol myristate acetate were able to rapidly destroy autologous erythrocyte targets. Monocyte-mediated cytotoxicity was related to phorbol myristate acetate concentration and monocyte number. Purified preparations of lymphocytes were incapable of mediating erythrocyte lysis in this system. The ability of phorbol myristate acetate-stimulated monocytes to lyse erythrocyte targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for superoxide anion and hydrogen peroxide in the cytotoxic event, a variety of hydroxyl radical and singlet oxygen scavengers did not effect cytolysis. However, tryptophan significantly inhibited cytotoxicity. The myeloperoxidase inhibitor cyanide enhanced erythrocyte destruction, whereas azide reduced it modestly. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase system. We conclude that monocytes, stimulated with phorbol myristate acetate, generate superoxide anion and hydrogen peroxide, which together play an integral role in this cytotoxic mechanism.

  4. Esophageal involvement in eosinophilic gastroenteritis

    Energy Technology Data Exchange (ETDEWEB)

    Matzinger, M A; Daneman, A

    1983-02-01

    The radiologic appearance of esophageal involvement due to eosinophilic gastroenteritis in a 15-year-old boy is presented. The lower two thirds of the esophagus was narrowed and the peristalsis diminished. The mucosa appeared smooth. This is the fourth reported case of esophageal involvement in eosinophilic gastroenteritis.

  5. Eosinophils, probiotics, and the microbiome.

    Science.gov (United States)

    Rosenberg, Helene F; Masterson, Joanne C; Furuta, Glenn T

    2016-11-01

    There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored. © Society for Leukocyte Biology.

  6. Transcriptome analysis of monocyte-HIV interactions

    Directory of Open Access Journals (Sweden)

    Tran Huyen

    2010-06-01

    Full Text Available Abstract Background During HIV infection and/or antiretroviral therapy (ART, monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions. Results Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19 for the development of the abacavir hypersensitivity reaction were suggested. Conclusions Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV. Background Both macrophages and T lymphocyte subsets express the CD4 receptor and either the CXCR4 and/or the CCR5 coreceptor which confer susceptibility to infection with the Human Immunodeficiency Virus

  7. Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry

    International Nuclear Information System (INIS)

    Weil, G.J.; Chused, T.M.

    1981-01-01

    Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence-activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis

  8. Eosinophilic Esophagitis (EoE)

    Science.gov (United States)

    ... excluded usually include dairy, egg, wheat, soy, peanut, tree nuts and fish/shellfish. These diets have been ... minorities » IgE ab to minor milk proteins may identify the proteins that are relevant to eosinophilic esophagitis » ...

  9. Eosinophilic Esophagitis: Symptoms and Causes

    Science.gov (United States)

    ... to GERD medication Failure to thrive (poor growth, malnutrition and weight loss) When to see a doctor ... Originally, eosinophilic esophagitis was thought to be a childhood disease, but now it is known to be ...

  10. Eosinophilic Esophagitis: Diagnosis and Treatment

    Science.gov (United States)

    ... as fatty or fried foods, tomato sauce, alcohol, chocolate, mint, garlic, onion, and caffeine, may make heartburn ... the waist up. Alternative medicine No alternative medicine therapies have been proved to treat eosinophilic esophagitis. Still, ...

  11. Radiation effects on cultured human monocytes and on monocyte-derived macrophages

    International Nuclear Information System (INIS)

    Buescher, E.S.; Gallin, J.I.

    1984-01-01

    Prior to administration, leukocyte transfusions are commonly irradiated with up to 5,000 R to eliminate lymphocytes and thereby prevent graft-versus-host disease in the recipient. It has been widely believed that phagocytes are resistant to this irradiation. In a recent report, it was noted that phagocyte oxidative metabolism was compromised during preparation of white cells for transfusion. As part of the effort to examine the basis for this inhibition of phagocyte function during white cell preparation, an assessment was made of the effects of irradiation on the long-lived monocytes that have been shown to persist at inflammatory foci posttransfusion. Human monocytes were irradiated for up to 3 min, receiving 2,500-5,000 R. This irradiation damaged human monocytes, significantly decreasing their in vitro survival for the first 3 wk of culture, and growth as assessed by two-dimensional cell size measurements during the first 2 wk of culture. Despite smaller cell size, total cell protein was significantly increased over time in irradiated cultures. Extracellular release of lysozyme and beta-glucuronidase per cell was not affected by irradiation, but extracellular lactate dehydrogenase (LDH) release was significantly increased after irradiation. Irradiated monocytes killed Listeria monocytogenes at a slower rate than the nonirradiated controls. Thus, the data indicate that irradiation in doses used to prevent graft-versus-host disease in leukocyte transfusion recipients has a deleterious effect on in vitro human monocyte survival and function

  12. Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood

    DEFF Research Database (Denmark)

    2013-01-01

    blood when compared to adherence to granulocytes, T-lymphocytes, B- lymphocytes and/or NK cells in freshly drawn blood, to a lipid-based pharmaceutical composition comprising said liposomes and their use in monocytic associated prophylaxis, treatment or amelioration of a condition such as cancer...

  13. Maturation and demise of human primary monocytes by carbon nanotubes

    Science.gov (United States)

    De Nicola, Milena; Mirabile Gattia, Daniele; Traversa, Enrico; Ghibelli, Lina

    2013-06-01

    The possibility of exploiting carbon nanotubes (CNT) in biomedical practices requires thorough analysis of the chemical or bulk effects they may exert on the immune system, the complex network that recognizes and eliminates foreign particles. In particular, the phagocytosing ability of cells belonging to the monocyte/macrophage lineage may render these immune cells an ideal toxicological target of pristine CNT, which may form aggregates of size exceeding monocyte/macrophage phagocytosing plasticity. To shed light on this issue, we analyzed the effects that pristine multi-walled CNT (MWCNT) without metal or biological impurities exert on survival and activation of freshly explanted human peripheral blood monocytes, analyzing in parallel the non-phagocytosing lymphocytes, and using graphite as control carbon material. MWCNT (diameter 10-50 nm, length up to 10 μm) exert two different toxic effects on mononuclear leukocytes: a minor apoptogenic effect (on lymphocytes > monocytes), and a major, apoptosis-independent effect that exclusively and deeply affect monocyte homeostasis. Analysis of monocyte number, adhesion, redox equilibrium, and the differentiation markers CD14 and CD11b reveals that MWCNT cause the selective disappearance of phagocytosis-competent monocytes by mechanisms related to the presence of large nanoparticle aggregates, suggesting phenomena of bulk toxicity possibly consisting of frustrated phagocytosis. At the same time, MWCNT stimulate adhesion of the phagocytosis-incompetent monocytes, and their differentiation toward a peculiar maturation asset. These observations point out novel mechanisms of CNT toxicity, renewing concerns that they may impair the innate immune system deranging the inflammatory responses.

  14. Maturation and demise of human primary monocytes by carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    De Nicola, Milena, E-mail: milena.de.nicola@uniroma2.it [University of Rome ' Tor Vergata' , Department of Biology (Italy); Mirabile Gattia, Daniele, E-mail: daniele.mirabile@enea.it [UTTMAT, ENEA-C.R. Casaccia (Italy); Traversa, Enrico, E-mail: Enrico.Traversa@kaust.edu.sa [King Abdullah University of Science and Technology (KAUST), Division of Physical Science and Engineering (Saudi Arabia); Ghibelli, Lina, E-mail: ghibelli@uniroma2.it [University of Rome ' Tor Vergata' , Department of Biology (Italy)

    2013-06-15

    The possibility of exploiting carbon nanotubes (CNT) in biomedical practices requires thorough analysis of the chemical or bulk effects they may exert on the immune system, the complex network that recognizes and eliminates foreign particles. In particular, the phagocytosing ability of cells belonging to the monocyte/macrophage lineage may render these immune cells an ideal toxicological target of pristine CNT, which may form aggregates of size exceeding monocyte/macrophage phagocytosing plasticity. To shed light on this issue, we analyzed the effects that pristine multi-walled CNT (MWCNT) without metal or biological impurities exert on survival and activation of freshly explanted human peripheral blood monocytes, analyzing in parallel the non-phagocytosing lymphocytes, and using graphite as control carbon material. MWCNT (diameter 10-50 nm, length up to 10 {mu}m) exert two different toxic effects on mononuclear leukocytes: a minor apoptogenic effect (on lymphocytes > monocytes), and a major, apoptosis-independent effect that exclusively and deeply affect monocyte homeostasis. Analysis of monocyte number, adhesion, redox equilibrium, and the differentiation markers CD14 and CD11b reveals that MWCNT cause the selective disappearance of phagocytosis-competent monocytes by mechanisms related to the presence of large nanoparticle aggregates, suggesting phenomena of bulk toxicity possibly consisting of frustrated phagocytosis. At the same time, MWCNT stimulate adhesion of the phagocytosis-incompetent monocytes, and their differentiation toward a peculiar maturation asset. These observations point out novel mechanisms of CNT toxicity, renewing concerns that they may impair the innate immune system deranging the inflammatory responses.

  15. Maturation and demise of human primary monocytes by carbon nanotubes

    International Nuclear Information System (INIS)

    De Nicola, Milena; Mirabile Gattia, Daniele; Traversa, Enrico; Ghibelli, Lina

    2013-01-01

    The possibility of exploiting carbon nanotubes (CNT) in biomedical practices requires thorough analysis of the chemical or bulk effects they may exert on the immune system, the complex network that recognizes and eliminates foreign particles. In particular, the phagocytosing ability of cells belonging to the monocyte/macrophage lineage may render these immune cells an ideal toxicological target of pristine CNT, which may form aggregates of size exceeding monocyte/macrophage phagocytosing plasticity. To shed light on this issue, we analyzed the effects that pristine multi-walled CNT (MWCNT) without metal or biological impurities exert on survival and activation of freshly explanted human peripheral blood monocytes, analyzing in parallel the non-phagocytosing lymphocytes, and using graphite as control carbon material. MWCNT (diameter 10–50 nm, length up to 10 μm) exert two different toxic effects on mononuclear leukocytes: a minor apoptogenic effect (on lymphocytes > monocytes), and a major, apoptosis-independent effect that exclusively and deeply affect monocyte homeostasis. Analysis of monocyte number, adhesion, redox equilibrium, and the differentiation markers CD14 and CD11b reveals that MWCNT cause the selective disappearance of phagocytosis-competent monocytes by mechanisms related to the presence of large nanoparticle aggregates, suggesting phenomena of bulk toxicity possibly consisting of frustrated phagocytosis. At the same time, MWCNT stimulate adhesion of the phagocytosis-incompetent monocytes, and their differentiation toward a peculiar maturation asset. These observations point out novel mechanisms of CNT toxicity, renewing concerns that they may impair the innate immune system deranging the inflammatory responses.

  16. Maturation and demise of human primary monocytes by carbon nanotubes

    KAUST Repository

    De Nicola, Milena D.

    2013-05-17

    The possibility of exploiting carbon nanotubes (CNT) in biomedical practices requires thorough analysis of the chemical or bulk effects they may exert on the immune system, the complex network that recognizes and eliminates foreign particles. In particular, the phagocytosing ability of cells belonging to the monocyte/macrophage lineage may render these immune cells an ideal toxicological target of pristine CNT, which may form aggregates of size exceeding monocyte/macrophage phagocytosing plasticity. To shed light on this issue, we analyzed the effects that pristine multi-walled CNT (MWCNT) without metal or biological impurities exert on survival and activation of freshly explanted human peripheral blood monocytes, analyzing in parallel the non-phagocytosing lymphocytes, and using graphite as control carbon material. MWCNT (diameter 10-50 nm, length up to 10 μm) exert two different toxic effects on mononuclear leukocytes: a minor apoptogenic effect (on lymphocytes > monocytes), and a major, apoptosis-independent effect that exclusively and deeply affect monocyte homeostasis. Analysis of monocyte number, adhesion, redox equilibrium, and the differentiation markers CD14 and CD11b reveals that MWCNT cause the selective disappearance of phagocytosis-competent monocytes by mechanisms related to the presence of large nanoparticle aggregates, suggesting phenomena of bulk toxicity possibly consisting of frustrated phagocytosis. At the same time, MWCNT stimulate adhesion of the phagocytosis-incompetent monocytes, and their differentiation toward a peculiar maturation asset. These observations point out novel mechanisms of CNT toxicity, renewing concerns that they may impair the innate immune system deranging the inflammatory responses. © 2013 Springer Science+Business Media Dordrecht.

  17. Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma.

    Science.gov (United States)

    Guerra, Evelyn Santos; Lee, Chrono K; Specht, Charles A; Yadav, Bhawna; Huang, Haibin; Akalin, Ali; Huh, Jun R; Mueller, Christian; Levitz, Stuart M

    2017-01-01

    Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and >90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment.

  18. External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma

    NARCIS (Netherlands)

    Wagener, A. H.; de Nijs, S. B.; Lutter, R.; Sousa, A. R.; Weersink, E. J. M.; Bel, E. H.; Sterk, P. J.

    2015-01-01

    Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic

  19. Eosinophilic Chronic Rhinosinusitis in Japan

    Directory of Open Access Journals (Sweden)

    Junichi Ishitoya

    Full Text Available ABSTRACT: Chronic rhinosinusitis is a heterogeneous disease. In Europe and the United States, it has recently been divided into two subgroups: chronic rhinosinusitis with nasal polyps (CRSwNP and chronic rhinosinusitis without nasal polyps (CRSsNP. The majority of CRSwNP cases have a strong tendency to recur after surgery and show eosinophil-dominant inflammation. However, this definition has proved difficult to apply in Japan and East Asia, because more than half of the CRSwNP cases do not exhibit eosinophil-dominant inflammation in these areas of the world. In Japan in the 1990s, refractory CRSwNP to the standard treatment was focused on in clinical studies and the term ''eosinophilic chronic rhinosinusitis'' (ECRS was introduced to identify this subgroup of chronic rhinosinusitis in 2001.ECRS is different from non-ECRS in terms of many clinical features: symptom appearance, occurrence site of nasal polyps, CT scan findings, the histology of nasal polyps, blood examination findings, clinical course after surgery, and co-morbid asthma, etc. In this review, we describe these clinical features and mention how to make a clinical diagnosis of ECRS as well as how to treat it. Finally, we discuss the pathophysiology of ECRS. The concept of ECRS in Japan would be applicable for CRSwNP in other countries including Europe and the United States. KEY WORDS: chronic rhinosinusitis, clinical feature, diagnosis, eosinophilic chronic rhinosinusitis, eosinophils

  20. Eosinophilic Esophagitis: MedlinePlus Health Topic

    Science.gov (United States)

    ... Esophagitis (EoE) (American Academy of Allergy, Asthma, and Immunology) Also in Spanish Latest News Eosinophilic Esophagitis May ... Pediatric and Adolescent Patients (American College of Gastroenterology) Topic Image Related Health Topics Eosinophilic Disorders Esophagus Disorders ...

  1. Immunological system and Schistosoma mansoni: co-evolutionary immunobiology. What is the eosinophil role in parasite-host relationship?

    Directory of Open Access Journals (Sweden)

    Henrique L Lenzi

    1997-12-01

    Full Text Available Schistosomes, ancestors and recent species, have pervaded many hosts and several phylogenetic levels of immunity, causing an evolutionary pressure to eosinophil lineage expression and response. Schistosoma mansoni adult worms have capitalized on the apparent adversity of living within the mesenteric veins, using the dispersion of eggs and antigens to other tissues besides intestines to set a systemic activation of several haematopoietic lineages, specially eosinophils and monocytes/macrophages. This activation occurs in bone marrow, spleen, liver, lymph nodes, omental and mesenteric milky spots (activation of the old or primordial and recent or new lymphomyeloid tissue, increasing and making easy the migration of eosinophils, monocytes and other cells to the intestinal periovular granulomas. The exudative perigranulomatous stage of the periovular reaction, which present hystolitic characteristics, is then exploited by the parasites, to release the eggs into the intestinal lumen. The authors hypothesize here that eosinophils, which have a long phylogenic story, could participate in the parasite - host co-evolution, specially with S. mansoni, operating together with monocytes/ macrophages, upon parasite transmission.

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

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

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

  3. Atypical presentations of eosinophilic fasciitis

    Directory of Open Access Journals (Sweden)

    Tulin Ergun

    2016-01-01

    Full Text Available Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

  4. CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection

    OpenAIRE

    van den Bosch, Thierry P. P.; Caliskan, Kadir; Kraaij, Marina D.; Constantinescu, Alina A.; Manintveld, Olivier C.; Leenen, Pieter J. M.; von der Th?sen, Jan H.; Clahsen-van Groningen, Marian C.; Baan, Carla C.; Rowshani, Ajda T.

    2017-01-01

    textabstractBackground: During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during rejection. Here, we aimed to define and correlate monocyte-macrophage endomyocardial tissue profiles obtained at rejection and time points prior to rejection, with corresponding serial blood samples ...

  5. Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits

    Science.gov (United States)

    CHOI, Gil Soon; OAK, Chulho; CHUN, Bong-Kwon; WILSON, Donald; JANG, Tae Won; KIM, Hee-Kyoo; JUNG, Mannhong; TUTKUN, Engin; PARK, Eun-Kee

    2014-01-01

    Titanium dioxide (TiO2) is increasingly widely used in industrial, commercial and home products. TiO2 aggravates respiratory symptoms by induction of pulmonary inflammation although the mechanisms have not been well investigated. We aimed to investigate lung inflammation in rabbits after intratracheal instillation of P25 TiO2. One ml of 10, 50 and 250 µg of P25 TiO2 was instilled into one of the lungs of rabbits, chest computed-tomography was performed, and bronchoalveolar lavage (BAL) fluid was collected before, at 1 and 24 h after P25 TiO2 exposure. Changes in inflammatory cells in the BAL fluids were measured. Lung pathological assay was also carried out at 24 h after P25 TiO2 exposure. Ground glass opacities were noted in both lungs 1 h after P25 TiO2 and saline (control) instillation. Although the control lung showed complete resolution at 24 h, the lung exposed to P25 TiO2 showed persistent ground glass opacities at 24 h. The eosinophil counts in BAL fluid were significantly increased after P25 TiO2 exposure. P25 TiO2 induced a dose dependent increase of eosinophils in BAL fluid but no significant differences in neutrophil and lymphocyte cell counts were detected. The present findings suggest that P25 TiO2 induces lung inflammation in rabbits which is associated with eosinophilic inflammation. PMID:24705802

  6. Prion protein induced signaling cascades in monocytes

    International Nuclear Information System (INIS)

    Krebs, Bjarne; Dorner-Ciossek, Cornelia; Schmalzbauer, Ruediger; Vassallo, Neville; Herms, Jochen; Kretzschmar, Hans A.

    2006-01-01

    Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP C ), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP C fusion proteins synthesized with a human Fc-tag. PrP C fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK 1,2 and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP C in monocytes and macrophages

  7. Human Eosinophils Express Functional CCR7

    Science.gov (United States)

    Ueki, Shigeharu; Estanislau, Jessica; Weller, Peter F.

    2013-01-01

    Human eosinophils display directed chemotactic activity toward an array of soluble chemokines. Eosinophils have been observed to migrate to draining lymph nodes in experimental models of allergic inflammation, yet it is unknown whether eosinophils express CCR7, a key chemokine receptor in coordinating leukocyte trafficking to lymph nodes. The purpose of this study is to demonstrate expression of CCR7 by human eosinophils and functional responses to CCL19 and CCL21, the known ligands of CCR7. Human eosinophils were purified by negative selection from healthy donors. CCR7 expression of freshly purified, unstimulated eosinophils and of IL-5–primed eosinophils was determined by flow cytometry and Western blot. Chemotaxis to CCL19 and CCL21 was measured in transwell assays. Shape changes to CCL19 and CCL21 were analyzed by flow cytometry and microscopy. Calcium fluxes of fluo-4 AM–loaded eosinophils were recorded by flow cytometry after chemokine stimulation. ERK phosphorylation of CCL19- and CCL21-stimulated eosinophils was measured by Western blot and Luminex assay. Human eosinophils expressed CCR7 as demonstrated by flow cytometry and Western blots. Eosinophils exhibited detectable cell surface expression of CCR7. IL-5–primed eosinophils exhibited chemotaxis toward CCL19 and CCL21 in a dose-dependent fashion. Upon stimulation with CCL19 or CCL21, IL-5–primed eosinophils demonstrated dose-dependent shape changes with polarization of F-actin and exhibited calcium influxes. Finally, primed eosinophils stimulated with CCL19 or CCL21 exhibited increased phosphorylation of ERK in response to both CCR7 ligands. We demonstrate that human eosinophils express CCR7 and have multipotent responses to the known ligands of CCR7. PMID:23449735

  8. Bach2 Controls Homeostasis of Eosinophils by Restricting the Type-2 Helper Function of T Cells.

    Science.gov (United States)

    Sato, Yuki; Kato, Hiroki; Ebina-Shibuya, Risa; Itoh-Nakadai, Ari; Okuyama, Ryuhei; Igarashi, Kazuhiko

    2017-03-01

    Bach2 is a transcription factor which represses its target genes and plays important roles in the differentiation of B and T lymphoid cells. Bach2-deficient (KO) mice develop severe pulmonary alveolar proteinosis, which is associated with increased numbers of granulocytes and T cells. Bach2 is essential for the regulation of T cells, but its role in the regulation of granulocytes is not clear. Here, we observed increased numbers of eosinophils but not neutrophils in the bone marrow, spleen, peripheral blood, and bronchoalveolar lavage fluids of Bach2 KO mice compared with those of wild-type (WT) mice. Upon co-transplantation of the bone marrow cells from CD45.2 Bach2 KO and CD45.1/CD45.2 double-positive WT mice to irradiated WT CD45.1/CD45.2 mice, the reconstituted numbers of eosinophils were similar between Bach2 KO and WT cells. These results showed that the deficiency of Bach2 in eosinophils did not directly drive the differentiation of eosinophils. To investigate the effect of Bach2 KO CD4 + T cells upon eosinophils, we analyzed Rag2/Bach2-double deficient (dKO) mice which lack lymphocytes including CD4 + T cells. Rag2/Bach2 dKO mice did not show any increase in the numbers of eosinophils. Importantly, Bach2 KO mice showed an increase of interleukin-5 (Il-5) in the sera compared with WT mice. These results suggest that up-regulated functions of CD4 + T cells including secretion of Il-5 resulted in proliferation and/or migration to peripheral tissues of eosinophils in Bach2 KO mice. We propose that Bach2 controls homeostasis of eosinophils via restricting the production of Il-5 in CD4 + T cells.

  9. Radioimmunoassay of human eosinophil cationic protein

    International Nuclear Information System (INIS)

    Venge, P.; Roxin, L.E.; Olsson, I.

    1977-01-01

    A radioimmunosorbent assay has been developed which allows the detection in serum of a cationic protein derived from eosinophil granulocytes. In 34 healthy individuals the mean level was 31 μg/l. with a range of 5 to 55 μg/l. The serum concentration of 'eosinophil' cationic protein was correlated (P<0.001) to the number of eosinophil granulocytes in peripheral blood. Quantitiation of 'eosinophil' cationic protein in serum might be useful in the study of eosinophil granulocyte turnover and function in vivo. (author)

  10. Eosinophils in mucosal immune responses

    Science.gov (United States)

    Travers, J; Rothenberg, M E

    2015-01-01

    Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

  11. Monocyte enrichment from leukapheresis products by using the Elutra cell separator.

    Science.gov (United States)

    Kim, Sinyoung; Kim, Hyun Ok; Baek, Eun-Jung; Choi, Youjeong; Kim, Han-Soo; Lee, Min-Geul

    2007-12-01

    Dendritic cells (DCs), used in clinical trials for cancer immunotherapy, require processing on an expanded scale to conform to current good manufacturing practice guidelines. This study evaluated a large-scale monocyte enrichment procedure with a commercially available cell separator (Elutra, Gambro BCT) and analyzed the capacity of enriched monocytes to differentiate into DCs. Mononuclear cells were collected in two patients with malignant melanoma and seven healthy donors by leukapheresis. Continuous-counterflow elutriation with the Elutra was performed to enrich and purify monocytes from leukapheresis products. Purity and recovery of enriched monocytes were analyzed by flow cytometry. DCs were generated from the elutriated monocytes and characterized by phenotypic surface marker and stimulatory capacity in an allogeneic mixed lymphocyte reaction. In the leukapheresis products, the total MNC count was 7.3 x 10(9) +/- 0.7 x 10(9) and the mean percentage of CD14+ monocytes was 16.5 +/- 3.8 percent, which increased to 68.9 +/- 7.4 percent after elutriation with the Elutra. The mean monocyte recovery was 94.3 percent. Elutriated monocytes were successfully cultured into phenotypically and functionally mature DCs. These results indicate that the Elutra cell separator allows for fast and easy enrichment of monocytes within a closed system. Furthermore, these monocytes can be differentiated into functionally mature DCs. Compared to plastic adherence and immunomagnetic selection methods, the elutriation procedure is inexpensive, efficient, and very effective.

  12. Monocyte functions in diabetes mellitus

    DEFF Research Database (Denmark)

    Geisler, C; Almdal, T; Bennedsen, J

    1982-01-01

    The aim of this study was to investigate the functions of monocytes obtained from 14 patients with diabetes mellitus (DM) compared with those of monocytes from healthy individuals. It was found that the total number of circulating monocytes in the 14 diabetic patients was lower than that from...... for the elucidation of concomitant infections in diabetic patients are discussed....

  13. Radiographic and pathologic observations of eosinophilic gastroenteritis

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Lae Won [Busan Nationa University College of Medicine, Busan (Korea, Republic of); Hong, Sook Hee; Lee, Jung Dal [Busan Gospel Hospital, Busan (Korea, Republic of)

    1974-10-15

    This report presents two cases with eosinophilic gastroenteritis in detail. The radiographic and pathologic features of eosinophilic gastroenteritis are summarized with emphasis on the differential diagnostic features. Radiographic eosinophilic gastritis should be differentiated from gastric carcinoma and lymphoma, and eosinophilic enteritis from intestinal tuberculosis and intussusception of the small bowel in Korea where these entities are prevent. Eosinophilic gastroenteritis is pathologically characterized by diffuse infiltration of the submucosa and muscle coats with eosinophilic in conjunction with hypertrophy of individual muscle fibers. This leads to thickening of the gastrointestinal wall resulting in narrowing and obstruction of the lumen. Eosinophilic venulitis is another characteristic feature which is helpful for differentiation this entity from a parasitic infection.

  14. Radiographic and pathologic observations of eosinophilic gastroenteritis

    International Nuclear Information System (INIS)

    Jung, Lae Won; Hong, Sook Hee; Lee, Jung Dal

    1974-01-01

    This report presents two cases with eosinophilic gastroenteritis in detail. The radiographic and pathologic features of eosinophilic gastroenteritis are summarized with emphasis on the differential diagnostic features. Radiographic eosinophilic gastritis should be differentiated from gastric carcinoma and lymphoma, and eosinophilic enteritis from intestinal tuberculosis and intussusception of the small bowel in Korea where these entities are prevent. Eosinophilic gastroenteritis is pathologically characterized by diffuse infiltration of the submucosa and muscle coats with eosinophilic in conjunction with hypertrophy of individual muscle fibers. This leads to thickening of the gastrointestinal wall resulting in narrowing and obstruction of the lumen. Eosinophilic venulitis is another characteristic feature which is helpful for differentiation this entity from a parasitic infection

  15. Acute eosinophilic pneumonia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Gyoo; Sik; Oh, Kyung Seung; Kim, Jong Min; Huh, Jin Do; Joh, Young Duk; Jang, Tae Won; Jung, Man Hong [Kosin Medical College, Busan (Korea, Republic of)

    1995-10-15

    Acute eosinophilic pneumonia is one of a recently described idiopathic eosinophilic lung disease, which differs from chronic eosinophilic pneumonia. Patients with acute eosinophilic pneumonia develop acute onset of dyspnea, hypoxemia, diffuse pulmonary infiltrates and pleural effusion on chest radiograph, and show an increase in number of eosinophils in bronchoalveolar lavage fluid or lung biopsy specimen. Prompt and complete response to corticosteroid therapy without any recurrence is characteristically seen in patient with this disease. Although the etiology of acute eosinophilic pneumonia is not known, it has been suggested to be related to a hypersensitivity phenomenon to an unidentified inhaled antigen. We report four cases of acute eosinophilic pneumonia presented with acute onset of dyspnea, diffuse pulmonary infiltrates on chest radiograph, and eosinophilia in bronchoalveolar lavage fluid in previously healthy adults.

  16. Acute eosinophilic pneumonia: a case report

    International Nuclear Information System (INIS)

    Jung, Gyoo; Sik; Oh, Kyung Seung; Kim, Jong Min; Huh, Jin Do; Joh, Young Duk; Jang, Tae Won; Jung, Man Hong

    1995-01-01

    Acute eosinophilic pneumonia is one of a recently described idiopathic eosinophilic lung disease, which differs from chronic eosinophilic pneumonia. Patients with acute eosinophilic pneumonia develop acute onset of dyspnea, hypoxemia, diffuse pulmonary infiltrates and pleural effusion on chest radiograph, and show an increase in number of eosinophils in bronchoalveolar lavage fluid or lung biopsy specimen. Prompt and complete response to corticosteroid therapy without any recurrence is characteristically seen in patient with this disease. Although the etiology of acute eosinophilic pneumonia is not known, it has been suggested to be related to a hypersensitivity phenomenon to an unidentified inhaled antigen. We report four cases of acute eosinophilic pneumonia presented with acute onset of dyspnea, diffuse pulmonary infiltrates on chest radiograph, and eosinophilia in bronchoalveolar lavage fluid in previously healthy adults

  17. Pre-operative irradiation of eosinophilic granuloma in the parotid area

    International Nuclear Information System (INIS)

    Kitahara, Satoshi; Toda, Yukio; Nakajima, Hisami; Takeyama, Isamu; Sodemoto, Yukio; Endo, Masaru

    1983-01-01

    Eosinophilic granuloma is thought to originate in the reticuloendothelial system and cannot clearly be distinguished from the surrounding tissue during operation. An eosinophilic granuloma in the parotid area was removed after 25 days of irradiation at a dosage of 10.0 Gy per 3 days. A thin capsule of connective tissue was observed after the tumor was cut in half. Then, histopathological studies were performed on this connective tissue to determine the effect of the irradiation. Histopathologically, at the periphery of the tissue, atrophy of lymphocytes and destruction of the lymphoid tissue, which were thought to result in an increase in the connective tissue, were observed. It was concluded that a small dose of pre-operative radiation on eosinophilic granuloma in the parotid area made the tumor small and produced a capsule around the tumor. (author)

  18. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle

    1999-01-01

    -assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

  19. Transfecting Human Monocytes with RNA.

    Science.gov (United States)

    Dannull, Jens; Nair, Smita K

    2016-01-01

    Targeting monocytes as a delivery system for drugs or nucleic acids, and thereby harnessing their natural tissue-infiltrating capacity, has become an area of intense investigation in both basic and clinical research. Herein we describe an efficient method to deliver mRNA (messenger RNA) or siRNA (small interfering RNA) into human monocytes by electroporation. This method can be applied in the laboratory to monocytes isolated via magnetic bead-based techniques, or in a clinical setting using monocytes that were collected via counterflow centrifugation elutriation using the Elutra(®) Cell Separation System. We further demonstrate that electroporation of monocytes with RNA represents a robust and highly relevant approach to modify monocytes for cell-based therapies. Last, the procedure described can readily be adapted to monocytes from different species, hence facilitating research in animal models.

  20. SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

    Science.gov (United States)

    Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

    2017-01-01

    Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

  1. Eosinophils in lichen sclerosus et atrophicus.

    Science.gov (United States)

    Keith, Phillip J; Wolz, Michael M; Peters, Margot S

    2015-10-01

    The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    International Nuclear Information System (INIS)

    Chou, Debbie L.; Gerriets, Joan E.; Schelegle, Edward S.; Hyde, Dallas M.; Miller, Lisa A.

    2011-01-01

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: ► Ozone can modulate the localization of eosinophils in infant allergic airways. ► Expression of eotaxins within the lung is affected by ozone and allergen exposure. ► CCL24 induction by ozone and allergen exposure is not linked to eosinophilia.

  3. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Debbie L.; Gerriets, Joan E. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Schelegle, Edward S.; Hyde, Dallas M. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States); Miller, Lisa A., E-mail: lmiller@ucdavis.edu [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States)

    2011-12-15

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: Black-Right-Pointing-Pointer Ozone can modulate the localization of eosinophils in infant allergic airways. Black-Right-Pointing-Pointer Expression of eotaxins within the lung is affected by ozone and allergen exposure. Black-Right-Pointing-Pointer CCL24 induction by

  4. Enhanced activation of eosinophils in peripheral blood and implications for eosinophilic esophagitis diagnosis.

    Science.gov (United States)

    Botan, Valéria; Dos Santos Borges, Tatiana Karla; Rocha Alves, Érica Alessandra; Claudino Pereira Couto, Shirley; Bender Kohnert Seidler, Heinrich; Muniz-Junqueira, Maria Imaculada

    2017-07-01

    Eosinophils are markers of the eosinophilic esophagitis (EoE) disease, and this work aimed to assess whether activation of eosinophils could be a noninvasive test to contribute for EoE diagnosis. The activation state of peripheral blood eosinophils in EoE patients and control subjects was assessed based on the morphological aspects of the eosinophil after adherence to slide. Cyclooxygenase-2 and 5-lipoxygenase expressions were evaluated by means of immunofluorescence microscopy to verify if and which eicosanoid pathway is triggered in eosinophils in blood in EoE. The eosinophils of patients with EoE were significantly more activated than those of control individuals. The lowest percentage of normal eosinophils for control subjects was 40%, while the highest percentage of eosinophils of normal aspect for patients with EoE was 32%. Considering 36% as a cutoff for normal eosinophils, this value differentiated all individuals with EoE from individuals without the disease with a sensitivity of 100%, considering the diagnosis of EoE as currently defined. Eosinophils of EoE patients showed higher expression of cyclooxygenase-2 than those of control subjects. The quantification of morphological changes in eosinophils is a feasible, easy, and reliable manner to identify EoE patients. Therefore, patients with symptoms of esophageal dysfunction showing higher than 36% activated eosinophils in peripheral blood could be a useful way to help definition and diagnostic criterion for EoE. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. Eritema anular eosinofílico en un adulto Eosinophilic anular erythema in an adult.

    Science.gov (United States)

    Lobo, Marta Aguado; Gonzalo, Elena Sierra; Jiménez-Reyes, José

    2017-10-15

    Eosinophilic annular erythema (EAE) is an uncommon eosinophilic dermatosis. Clinically it is characterized by recurrent episodes of annular or figurative plaques. The histopathological study shows a perivascular inflammatory infiltrate in the superficial and deep dermis, composed of lymphocytes and eosinophils. It was originally described in children. We report an adult woman who presented with recurrent erythematous annular plaques on the trunk and extremities. A biopsy showed a mainly perivascular lymphocytic infiltrate with numerous eosinophils in the dermis. Laboratory examinations revealed subclinical hypothyroidism. The lesions resolved with topical corticosteroid spontaneously after 3 months.El eritema anular eosinofílico (EAE) es una dermatosis eosinofílica poco frecuente. Clínicamente se caracteriza por episodios recurrentes de placas anulares o figuradas.El estudio histopatológico muestra un infiltrado inflamatorio en dermis superficial y profunda, de localización perivascular y compuesto por linfocitos y eosinófilos. Se describió originariamente en niños. Presentamos una mujer adulta con episodios recurrentes de placas anulares o figuradas en el tronco y extremidades. La biopsia mostró un infiltrado linfocítico perivascular con numerosos eosinófilos en la dermis. La analítica reveló la presencia de hipotiroidismo subclínico. Las lesiones se resolvieron después de tres meses de tratamiento con una crema de corticoesteriodes.

  6. Esophageal motility in eosinophilic esophagitis.

    Science.gov (United States)

    Weiss, A H; Iorio, N; Schey, R

    2015-01-01

    Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus and is a potential cause of dysphagia and food impaction, most commonly affecting young men. Esophageal manometry findings vary from normal motility to aperistalsis, simultaneous contractions, diffuse esophageal spasm, nutcracker esophagus or hypotonic lower esophageal sphincter (LES). It remains unclear whether esophageal dysmotility plays a significant role in the clinical symptoms of EoE. Our aim is to review the pathogenesis, diagnosis, and effect of treatment on esophageal dysmotility in EoE. A literature search utilizing the PubMed database was performed using keywords: eosinophilic esophagitis, esophageal dysmotility, motility, manometry, impedance planimetry, barium esophagogram, endoscopic ultrasound, and dysphagia. Fifteen studies, totaling 387 patients with eosinophilic esophagitis were identified as keeping in accordance with the aim of this study and included in this review. The occurrence of abnormal esophageal manometry was reported to be between 4 and 87% among patients with EoE. Esophageal motility studies have shown reduced distensibility, abnormal peristalsis, and hypotonicity of the LES in patients with EoE, which may also mimic other esophageal motility disorders such as achalasia or nutcracker esophagus. Studies have shown conflicting results regarding the presence of esophageal dysmotility and symptoms with some reports suggesting a higher rate of food impaction, while others report no correlation between motor function and dysphagia. Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on

  7. MR findings of eosinophilic granuloma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jong O; Yee, Mi Kyeung; Cho, Kil Ho [Yeungnam Univ. College of Medicine, Kyongsan (Korea, Republic of); Lee, Sung Moon [Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Lee, Young Hwan [Hyosung Catholic Univ. College of Medicine, Taegu (Korea, Republic of); Suh, Kyung Jin [Suhjoo MR Clinic, Taegu (Korea, Republic of)

    1999-06-01

    To describe the MR findings for the three phases of eosinophilic granuloma, as defined by Mirra's conventional radiographic criteria. Eighteen lesions in 14 patients with proven eosinophilic granuloma were retrospectively analyzed. Among this total, three vertebral lesions were excluded, and the remaining is were classified as early, middle, or late phase on the basis of Mirra's radiographic criteria. For each phase, we compared MR findings with regard to signal intensity, homogeneity, contrast enhancement, perilesional marrow edema, and soft tissue change. For the three vertebral lesions excluded because the application of radiographic criteria was difficult, MR findings for paravertebral soft tissue reaction and degree of cord compression were compared. Of the fifteen cases classified, eight were early phase, five were mid phase, and two were late phase. During each phase, all lesions except one, as seen on T1-weighted images(T1WI), showed iso-signal intensity. On T2WI, all lesions showed high signal intensity. Contrast study demonstrated marked contrast enhancement. Thus, no remarkable differences were found in the signal intensity degree of contrast enhancement of each phase. With regard to heterogeneity, this was demonstrated in most early phase lesions, reflecting necrosis and hemorrhage of those lesions. Soft tissue swelling was more severe during the early phase than the mid or late phase, but marrow edema was similar in each of the three phase. One of three patients with vertebraplana showed para-vertebral soft tissue swelling and cord compression, but this was not seen in the two other cases. For evalvating the extent of eosinophilic granuloma and its relationship with surrounding structures, MRI was superior to conventional radiography. During the early phase of the disease, lesions showed greater inhomogeneity and more aggressive soft tissue reaction than during the mid and late phase.The use of MRI for the evalvation of eosinophilic granuloma

  8. Eosinophilic fasciitis after parasite infection

    Directory of Open Access Journals (Sweden)

    Marta Oliveira

    2016-03-01

    Full Text Available Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non-parasitic infections or cancer.

  9. Evaluation of plasma eosinophil count and mean platelet volume in patients with coronary slow flow

    Directory of Open Access Journals (Sweden)

    Mehmet Demir

    2014-01-01

    Full Text Available OBJECTIVE: The pathophysiology of coronary slow flow has not been clearly defined, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis, have been reported. It is known that eosinophils play an important role in inflammation, endothelial dysfunction, and thrombosis. We aimed to compare the eosinophil counts of coronary slow flow patients versus healthy controls. METHODS: This study included 50 coronary slow flow patients (19 males, mean age 65.6±13.7 years and 30 healthy controls (10 males, mean age 57.86±11.6 years. These participants were evaluated using concurrent routine biochemical tests as well as neutrophil, lymphocyte, and eosinophil counts and mean platelet volume (MPV, which were obtained from the whole blood count. These parameters were compared between groups. RESULTS: The baseline characteristics of the study groups were comparable. The coronary slow flow patients had a higher mean platelet volume and eosinophil count than the control group (8.38±0.86 vs 6.28±1.6 fL and 0.31±0.42 vs 0.09±0.05; p<0.001 and 0.008, respectively. CONCLUSION: Our study demonstrated a relationship between eosinophil count and MPV in patients with coronary slow flow.

  10. In-flight Blood Analysis Technology for Astronaut Health Monitoring

    Data.gov (United States)

    National Aeronautics and Space Administration — Blood staining and testing procedure optimization: A 5-part WBC differential (Lymphocyte, Monocyte, Neutrophil, Eosinophil, and Basophil) assay using a...

  11. Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells

    OpenAIRE

    Stroncek, David F.; Lee, Daniel W.; Ren, Jiaqiang; Sabatino, Marianna; Highfill, Steven; Khuu, Hanh; Shah, Nirali N.; Kaplan, Rosandra N.; Fry, Terry J.; Mackall, Crystal L.

    2017-01-01

    Background Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Methods Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We ...

  12. The acute monocytic leukemias: multidisciplinary studies in 45 patients.

    Science.gov (United States)

    Straus, D J; Mertelsmann, R; Koziner, B; McKenzie, S; de Harven, E; Arlin, Z A; Kempin, S; Broxmeyer, H; Moore, M A; Menendez-Botet, C J; Gee, T S; Clarkson, B D

    1980-11-01

    The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

  13. Chronic eosinophilic pneumonia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Tae Haeng; Park, Jeong Hee; Lim, Jong Nam; Shin, Hyun Jun; Jeon, Hae Jeong [College of Medicine, Kon-Kuk University, Seoul (Korea, Republic of)

    1995-05-15

    Chronic eosinophilic pneumonia is a rare disease characterized by chronic infiltration of the lung with eosinophils, usually associated with peripheral eosinophilia. In 65% of cases, the chest radiograph shows typical nonsegmental air-space consolidation confined to the outer third of the lung, and in 25% of cases, the 'photographic negative of pulmonary edema' Typical lung manifestations with peripheral eosinophilia are characteristic of chronic eosinophilic pneumonia. In the remaining cases, radiographic findings are nonspecific and require lung biopsy for confirmation. We report a case of chronic eosinophilic pneumonia in which chest radiograph and CT scans revealed bilateral patchy or diffuse opacity with nodules scattered throughout the lungs.

  14. Eosinophils: changing perspectives in health and disease

    Science.gov (United States)

    Rosenberg, Helene F.; Dyer, Kimberly D.; Foster, Paul S.

    2015-01-01

    Eosinophils have been traditionally perceived as largely end-stage, cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular basis of development, trafficking and degranulation of eosinophils have provided a better understanding of the role of these cells in promoting homeostasis through their immunomodulatory functions. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of disease, including asthma and primary hypereosinophilic syndromes, and also a more complete appreciation of their activities in parasitic infection. PMID:23154224

  15. Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

    Science.gov (United States)

    ... associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description PDGFRB -associated chronic eosinophilic leukemia is a type of cancer of blood-forming ...

  16. Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5)

    International Nuclear Information System (INIS)

    Campbell, H.D.; Tucker, W.Q.J.; Hort, Y.; Martinson, M.E.; Mayo, G.; Clutterbuck, E.J.; Sanderson, C.J.; Young, I.G.

    1987-01-01

    The human eosinophil differentiation factor (EDF) gene was cloned from a genomic library in λ phage EMBL3A by using a murine EDF cDNA clone as a probe. The DNA sequence of a 3.2-kilobase BamHI fragment spanning the gene was determined. The gene contains three introns. The predicted amino acid sequence of 134 amino acids is identical with that recently reported for human interleukin 5 but shows no significant homology with other known hemopoietic growth regulators. The amino acid sequence shows strong homology (∼ 70% identity) with that of murine EDF. Recombinant human EDF, expressed from the human EDF gene after transfection into monkey COS cells, stimulated the production of eosinophils and eosinophil colonies from normal human bone marrow but had no effect on the production of neutrophils or mononuclear cells (monocytes and lymphoid cells). The apparent specificity of human EDF for the eosinophil lineage in myeloid hemopoiesis contrasts with the properties of human interleukin 3 and granulocyte/macrophage and granulocyte colony-stimulating factors but is directly analogous to the biological properties of murine EDF. Human EDF therefore represents a distinct hemopoietic growth factor that could play a central role in the regulation of eosinophilia

  17. Peritumoral eosinophils predict recurrence in colorectal cancer.

    Science.gov (United States)

    Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord

    2015-03-01

    In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; Peosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising

  18. Activation states of blood eosinophils in asthma

    Science.gov (United States)

    Johansson, Mats W.

    2014-01-01

    Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or “primed”, or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease. PMID:24552191

  19. Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

    Science.gov (United States)

    ... link) Genetic Testing Registry: Idiopathic hypereosinophilic syndrome Other Diagnosis and Management Resources (3 links) Cancer.Net: Leukemia - Eosinophilic: Treatment MedlinePlus Encyclopedia: Eosinophil Count - Absolute Seattle ...

  20. Up-regulated dipeptidyl-peptidase IV (CD26) on monocytes was unaffected by effective DMARD treatment in early steroid and DMARD-naive rheumatoid arthritis

    DEFF Research Database (Denmark)

    Ellingsen, Torkell Juulsgaad; Hansen, I; Thorsen, J

    2012-01-01

    To study the CD26 density on monocytes and CD4+ T-lymphocytes in steroid and DMARD-naïve, early rheumatoid arthritis (RA) patients and to analyse for correlations with disease activity, including long-term radiographic progression.......To study the CD26 density on monocytes and CD4+ T-lymphocytes in steroid and DMARD-naïve, early rheumatoid arthritis (RA) patients and to analyse for correlations with disease activity, including long-term radiographic progression....

  1. Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell Death.

    Science.gov (United States)

    Ueki, Shigeharu; Ohta, Nobuo; Takeda, Masahide; Konno, Yasunori; Hirokawa, Makoto

    2017-05-01

    Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is known about the fate of the eosinophils and aftermath of their cell death. We discuss the possibility that eosinophils undergo non-apoptotic cell death that worsens tissue damage and increases effusion viscosity. Unlike chronic otitis media, EOM is strongly associated with an allergic background. Corticosteroids are currently the only effective pharmacological treatment, and surgical intervention is often required. Mucosal eosinophils infiltrate extensively into the middle ear cavity where they are stimulated by locally produced activators including interleukin-5 and eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a major fate of activated eosinophils in vivo. Recent data revealed cytolysis could be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal cell death involving total cell degranulation and development of sticky chromatin structures (extracellular traps (ETs)). The characteristics of eosinophil- and neutrophil-derived ET polymers might contribute to the difference in viscosity of secretions between EOM and common chronic otitis media. The extracellular products remaining after eosinophil ETosis are an important aspect of EOM pathology. The concept of ETosis also has novel implications for potential therapeutic modalities in various eosinophilic disorders.

  2. Osseous eosinophilic granuloma in children

    International Nuclear Information System (INIS)

    Leblan, I.; Gaucher, H.; Marinard, L.; Galloy, M.A.; Phi, I.N.; Hoeffel, J.C.

    2001-01-01

    Eosinophilic granuloma of bone or Langerhans cell histiocytosis is mostly uni-focal. It appears on plain X Ray as a solitary destructive lesion of long bones or flat bones. CT is useful to define the extension to the cortical bone and also to precisely localize the lesion when the anatomy is complex (hip, spine, base of the skull). MR is very useful in case of more aggressive lesions when there is extension to soft tissues. Differential diagnosis includes circumscribed osteitis and tumors prognosis is more serious in case of multiple lesions. (authors)

  3. Eosinophilic dermatosis of hematologic malignancy.

    Science.gov (United States)

    Martires, Kathryn; Callahan, Shields; Terushkin, Vitaly; Brinster, Nooshin; Leger, Marie; Soter, Nicholas A

    2016-12-15

    We report a 68-year-old woman with chroniclymphocytic leukemia, who developed numerous,pruritic, edematous, and vesicobullous skin lesionsof the face and extremities over the course of severalmonths. The diagnosis of eosinophilic dermatosis ofhematologic malignancy (EDHM) was made basedon the clinical history and histopathologic features.Owing to the possible link between EDHM and amore aggressive underlying CLL, she was startedagain on chemotherapy. This case serves as areminder that, although the precise pathogenesis ofEDHM remains unclear, the paraneoplastic disorderis the result of immune dysregulation. Patientswho develop EDHM should undergo prompthematologic/oncologic evaluation.

  4. Eosinophilic Mucin Otomastoiditis and Otopolyposis: A Progressive Form of Eosinophilic Otitis Media.

    Science.gov (United States)

    Azadarmaki, Roya; Westra, William; Prasad, Sanjay

    2015-09-01

    The purpose of this study is to introduce and define a disease entity on a continuum of eosinophilic otitis media: eosinophilic mucin otomastoiditis and otopolyposis. A case of a 66-year-old woman with complicated chronic otitis media is reported. A literature review of the National Library of Medicine's online database, with a focus on eosinophilic otitis media and eosinophilic mucin rhinosinusitis, was performed. The authors report the case of a 66-year-old woman with a history of asthma, chronic rhinosinusitis, nasal polyposis, and chronic otitis media who presented with allergic middle ear mucin and otic polyps. Treatment involved a tympanomastoidectomy with removal of otic polyps and steroid therapy. Eosinophilic mucin otomastoiditis with otopolyposis is a disease entity on a continuum of eosinophilic otitis media. This disease process shares similarities with eosinophilic mucin rhinosinusitis. Otic polypectomy and steroids are suggested therapeutic measures. © The Author(s) 2015.

  5. GWAS identifies four novel eosinophilic esophagitis loci

    NARCIS (Netherlands)

    Sleiman, Patrick M. A.; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J.; Furuta, Glenn T.; Spergel, Jonathan M.; Hakonarson, Hakon

    2014-01-01

    Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the oesophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which

  6. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  7. Clinical characteristics of eosinophilic asthma exacerbations

    DEFF Research Database (Denmark)

    Bjerregaard, Asger; Laing, Ingrid A; Backer, Vibeke

    2017-01-01

    blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non-eosinophilic exacerbation as NEE). RESULTS: A total of 47 patients were enrolled; 37 (79%) had successful sputum induction...... at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P...... = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %-eosinophils (ρ = 0.57, P

  8. Eosinophils in helminth infection: defenders and dupes

    Science.gov (United States)

    Huang, Lu; Appleton, Judith A.

    2016-01-01

    Eosinophilia is a central feature of the host response to helminth infection. Larval stages of parasitic worms are killed in vitro by eosinophils in the presence of specific antibodies or complement. These findings established host defense as the paradigm for eosinophil function. Recently, studies in eosinophil-ablated mouse strains have revealed an expanded repertoire of immunoregulatory functions for this cell. Other reports document crucial roles for eosinophils in tissue homeostasis and metabolism, processes that are central to the establishment and maintenance of parasitic worms in their hosts. In this review, we summarize current understanding of the significance of eosinophils at the host-parasite interface, highlighting their distinct functions during primary and secondary exposure. PMID:27262918

  9. Functions of tissue-resident eosinophils.

    Science.gov (United States)

    Weller, Peter F; Spencer, Lisa A

    2017-12-01

    Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, 'non-effector' functions in health and disease.

  10. Coccidioidomycosis Masquerading as Eosinophilic Ascites

    Directory of Open Access Journals (Sweden)

    Kourosh Alavi

    2015-01-01

    Full Text Available Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as “Valley Fever,” is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA. A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG, PMN count >250/mm3, and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination.

  11. Coccidioidomycosis Masquerading as Eosinophilic Ascites.

    Science.gov (United States)

    Alavi, Kourosh; Atla, Pradeep R; Haq, Tahmina; Sheikh, Muhammad Y

    2015-01-01

    Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as "Valley Fever," is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA). A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG), PMN count >250/mm(3), and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination.

  12. The Pathophysiology of Eosinophilic Esophagitis

    Directory of Open Access Journals (Sweden)

    Daniel Avi Lemberg

    2014-05-01

    Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised by esophageal eosinophilia (>15eos/hpf, lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with TGF-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.

  13. [Eosinophilic pleural effusion possibly induced by fibrin sealant].

    Science.gov (United States)

    Kambayashi, Takatoyo; Suzuki, Takashi

    2012-02-01

    A 74-year-old man underwent right upper lobectomy for the lung cancer and bullectomy of right lower lobe. Fibrin sealant was used for sealing the excision line. The increase of the pleural effusion with increasing C-reactive protein( CRP) and eosinophilia was noted at the 17th day after the operation. The pleural effusion was transparent and yellowish colored suggesting transudatory liquid. The eosinophil in the pleural effusion was as high as 14%. The drainage of the pleural effusion was performed for 2 days resulting in disappearing the abnormal accumulation without any additional treatment. The cause of pleural effusion was supposed to be fibrin sealant by a positive result of the drug lymphocyte stimulation test.

  14. Blood Eosinophil and Basophil Values Before and After Surgery for Eosinophilic-type Sinonasal Polyps.

    Science.gov (United States)

    Brescia, Giuseppe; Parrino, Daniela; Zanotti, Claudia; Tealdo, Giulia; Barion, Umberto; Sfriso, Paolo; Marioni, Gino

    2018-01-01

    Background Blood eosinophil and basophil levels have recently been considered for the purpose of endotyping chronic rhinosinusitis with nasal polyps (CRSwNP). Histologically, eosinophilic-type CRSwNPs have been associated with high recurrence rates after treatment. Objective The present study was the first to compare blood eosinophil and basophil counts in eosinophilic-type CRSwNP patients before and after endoscopic sinus surgery. Methods The study concerned 79 consecutive patients with histologically confirmed eosinophilic-type CRSwNP treated with endoscopic sinus surgery. Results A significant drop in mean blood eosinophil counts and percentages occurred from before to after endoscopic sinus surgery in the cohort as a whole. Mean blood eosinophil counts and percentages were also reduced after surgery in the subcohorts of CRSwNP patients with (i) asthma, (ii) aspirin-exacerbated respiratory disease (AERD), and (iii) no allergy. Although blood eosinophil and basophil counts correlated directly before and after surgery, a statistical reduction in blood basophil counts and percentages after surgery emerged only in the subcohort of nonallergic CRSwNP patients. Conclusion Endoscopic sinus surgery can clear polyps, remove inflammatory tissue, and reduce inflammatory cytokine levels. Consistently with the biological mechanism described, endoscopic sinus surgery could coincide with a reduction in blood eosinophils in eosinophilic-type CRSwNP.

  15. Clinical features of so-called eosinophilic rhinosinusitis. With a view to screening for eosinophilic rhinosinusitis

    International Nuclear Information System (INIS)

    Sakuma, Yasunori; Ishitoya, Junichi; Kimura, Machiko; Hirose, Shouji; Takahashi, Masahiro; Tsukuda, Mamoru

    2006-01-01

    The concept of so-called eosinophilic sinusitis has recently come to be understood, but since the definition and the diagnostic criteria for this intractable form of sinusitis are unclear, we reviewed the clinical features of 104 patients (16 with eosinophilic sinusitis and 88 with non-eosionphilic sinusitis) who underwent endonasal sinus surgery in our department. So-called eosinophilic sinusitis was usually accompanied by severe bronchial asthma, and the characteristic clinical findings of so-called eosinophilic sinusitis were an increase in peripheral blood eosinophil count, a paranasal sinus shadow in computed tomograms (CT score), and a high ethmoid sinus/maxillary sinus score ratio (E/M ratio) in our study. We determined the cutoff value to review sensitivity, specificity and correct diagnosis rate in screening for eosinophilic sinusitis. When we judged using three cutoff values, a peripheral blood eosinophil count≥500/μ1, CT score≥13 and E/M ratio≥1, a sensitivity of 69%, specificity of 97% and correct diagnosis rate of 81%. On the other hand, when we judged using two cutoff value, peripheral blood eosinophil count≥500/μ1 and E/M ratio≥1, sensitivity of 75%, specificity of 94% and correct diagnosis rate of 88%. Because all three studies can be performed in outpatient clinics, we concluded that they are useful as a method of screening for so-called eosinophilic sinusitis without the need for histological examinations for eosinophil infiltration of nasal polyps in biopsy specimens. (author)

  16. Inability of newborns' or pregnant women's monocytes to suppress pokeweed mitogen-induced responses

    International Nuclear Information System (INIS)

    Durandy, A.; Fischer, A.; Griscelli, C.

    1982-01-01

    Although an excess of human adult blood adherent cells inhibits the pokeweed mitogen- (PWM) induced normal adult lymphocyte proliferation and B cell maturation into immunoglobulin-containing cells (ICC), adherent cells collected from newborn infants or pregnant women at time of delivery were unable to exert a similar suppressor activity. After activation by Concanavalin A (Con A), newborns' and pregnant women's adherent cells acquired a suppressor activity comparable to that of control adult adherent cells. The adherent suppressor cell was shown to be radioresistant (3000 rad), indicating its probable monocytic orgin. Both monocyte-suppressor activities (MSA) observed in adulthood (spontaneously) and in the neonatal period (after activation) were dependent on prostaglandin E 2 (PGE 2 ) secretion, because they were abolished by indomethacin or a specific anti-PGE 2 anti-serum. Expression of MSA appeared to be under a negative regulation exerted by naturally occurring T suppressor lymphocytes present in the blood of newborns or pregnant women, because incubation of adult monocytes or Con A-activated newborn monocytes with newborns' or pregnant women's T lymphocytes resulted in a dramatic decrease of their MSA. These results strongly suggest that the lack of MSA in the neonatal period and in late pregnancy is a consequence of activation of T suppressor lymphocytes

  17. Eosinophils: The unsung heroes in cancer?

    Science.gov (United States)

    Varricchi, Gilda; Galdiero, Maria Rosaria; Loffredo, Stefania; Lucarini, Valeria; Marone, Giancarlo; Mattei, Fabrizio; Marone, Gianni; Schiavoni, Giovanna

    2018-01-01

    Prolonged low-grade inflammation or smoldering inflammation is a hallmark of a cancer. Eosinophils are components of the immune microenvironment that modulates tumor initiation and progression. Although canonically associated with a detrimental role in allergic disorders, these cells can induce a protective immune response against helminthes, viral and bacterial pathogens. Eosinophils are a source of anti-tumorigenic (e.g., TNF-α, granzyme, cationic proteins, and IL-18) and protumorigenic molecules (e.g., pro-angiogenic factors) depending on the milieu. In several neoplasias (e.g., melanoma, gastric, colorectal, oral and prostate cancer) eosinophils play an anti-tumorigenic role, in others (e.g., Hodgkin's lymphoma, cervical carcinoma) have been linked to poor prognosis, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of eosinophils and their mediators could be cancer-dependent. The microlocalization (e.g., peritumoral vs intratumoral) of eosinophils could be another important aspect in the initiation/progression of solid and hematological tumors. Increasing evidence in experimental models indicates that activation/recruitment of eosinophils could represent a new therapeutic strategy for certain tumors (e.g., melanoma). Many unanswered questions should be addressed before we understand whether eosinophils are an ally, adversary or neutral bystanders in different types of human cancers.

  18. Eosinophils: important players in humoral immunity.

    Science.gov (United States)

    Berek, C

    2016-01-01

    Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. Recently, however, it has become clear that eosinophils also play crucial non-inflammatory roles in the generation and maintenance of adaptive immune responses. Eosinophils, being a major source of the plasma cell survival factor APRIL (activation and proliferation-induced ligand), are essential not only for the long-term survival of plasma cells in the bone marrow, but also for the maintenance of these cells in the lamina propria which underlies the gut epithelium. At steady state under non-inflammatory conditions eosinophils are resident cells of the gastrointestinal tract, although only few are present in the major organized lymphoid tissue of the gut - the Peyer's patches (PP). Surprisingly, however, lack of eosinophils abolishes efficient class-switching of B cells to immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are required to generate and to maintain mucosal IgA plasma cells, and as a consequence their absence leads to a marked reduction of IgA both in serum and in the gut-associated lymphoid tissues (GALT). Eosinophils thus have an essential part in long-term humoral immune protection, as they are crucial for the longevity of antibody-producing plasma cells in the bone marrow and, in addition, for gut immune homeostasis. © 2015 British Society for Immunology.

  19. Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

    Science.gov (United States)

    Minkoff, Marjorie Sue

    A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the

  20. Management guidelines of eosinophilic esophagitis in childhood

    DEFF Research Database (Denmark)

    Papadopoulou, A; Koletzko, S; Heuschkel, R

    2014-01-01

    OBJECTIVES: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field...... was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. RESULTS: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved...

  1. Decrease of Airway Allergies After Lung Transplantation Is Associated With Reduced Basophils and Eosinophils.

    Science.gov (United States)

    Niedzwiecki, M; Yamada, Y; Inci, I; Weder, W; Jungraithmayr, W

    2016-01-01

    Allergies are hypersensitive reactions of the immune system on antigen exposure similar to immune reactions after transplantation (Tx). Their activity can change after Tx. The lung as a transplantable organ is challenged two-fold, by antigens from the blood and the air environment. Herein we analyzed if airway allergies change after lung Tx. We systematically reviewed patients' airway allergies before and after lung Tx between 1992 and 2014. The course of lymphocytes, thrombocytes, and leukocytes, among them neutrophils, eosinophils, and basophils, was analyzed in patients in whom airway allergies have changed and in whom they did not change. From 362 lung transplanted patients, 44 patients had suffered from allergies before Tx (12.2%). In 20 of these patients (45.5%), airway allergies disappeared completely within 1 year after lung Tx and were persistently absent thereafter. In these patients, basophils and eosinophils decreased significantly (P allergies did not disappear. Leukocytes overall, and in particular, neutrophils, decreased significantly in patients whose allergy disappeared (P allergies disappeared in almost half of cases after lung Tx. Along with this reduction, basophils and eosinophils decreased as potentially responsible cells for this phenomenon. These findings may stimulate intensified research on basophils and eosinophils as major drivers of airway allergies. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Esophageal microbiome in eosinophilic esophagitis.

    Directory of Open Access Journals (Sweden)

    J Kirk Harris

    Full Text Available The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis.In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD and normal mucosa using the Esophageal String Test (EST. Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease.Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects.Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.

  3. Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma

    Directory of Open Access Journals (Sweden)

    Corrado Pelaia

    2018-01-01

    Full Text Available Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5, released by both T helper 2 (Th2 lymphocytes and group 2 innate lymphoid cells (ILC2. Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA.

  4. Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

    Science.gov (United States)

    Martins, Patrícia Rocha; Nascimento, Rodolfo Duarte; Lopes, Júlia Guimarães; Santos, Mônica Morais; de Oliveira, Cleida Aparecida; de Oliveira, Enio Chaves; Martinelli, Patrícia Massara; d'Ávila Reis, Débora

    2015-05-01

    Megacolon is frequently observed in patients who develop the digestive form of Chagas disease. It is characterized by dilation of the rectum-sigmoid portion and thickening of the colon wall. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase of infection. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we hypothesized that mast cells producing tryptase could influence the migration and the activation of eosinophils at the site, thereby contributing to the immunopathology of the chronic phase. We seek evidence of interactions between mast cells and eosinophils through (1) evaluation of eosinophils, regarding the expression of PAR2, a tryptase receptor; (2) correlation analysis between densities of mast cells and eosinophils; and (3) ultrastructural studies. The electron microscopy studies revealed signs of activation of mast cells and eosinophils, as well as physical interaction between these cells. Immunohistochemistry and correlation analyses point to the participation of tryptase immunoreactive mast cells in the migration and/or survival of eosinophils at the affected organ.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-11-01

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

  7. Genetics Home Reference: eosinophil peroxidase deficiency

    Science.gov (United States)

    ... play a role in regulating inflammation by fighting microbial invaders. EPX gene mutations reduce or prevent eosinophil ... GINA) Turns 10 All Bulletins Features What are genome editing and CRISPR-Cas9? What is direct-to- ...

  8. Imipenem/cilastatin-induced acute eosinophilic pneumonia.

    Science.gov (United States)

    Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei

    2016-03-04

    Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. 2016 BMJ Publishing Group Ltd.

  9. Eosinophilic esophagitis-endoscopic distinguishing findings

    OpenAIRE

    Caetano, Ana Célia; Gonçalves, Raquel; Rolanda, Carla

    2012-01-01

    Eosinophilic esophagitis (EE) is the most frequent condition found in a group of gastrointestinal disorders called eosinophilic gastrointestinal diseases. The hypothetical pathophysiological mechanism is related to a hypersensitivity reaction. Gastroesophageal reflux disease- like complaints not ameliorated by acid blockade or occasional symptoms of dysphagia or food impaction are likely presentations of EE. Due to its unclear pathogenesis and unspecific symptoms, it is difficult to diagnose ...

  10. Eosinophilic granuloma of the mandibular condyle

    International Nuclear Information System (INIS)

    Huh, Kyung Hoe; Yi, Won Jin; Oh, Sung Won; Lee, Sam Sun; Choi, Mun Kyung

    2008-01-01

    The present study reports a case of eosinophilic granuloma of the mandibular condyle. Eosinophilic granulomas on the mandibular condyle are very rare, but there are several common clinical and radiographic presentations. The clinical presentations involve swelling on preauricular area, limitation of opening, TMJ pain, etc. The radiographic presentations involve radiolucent lytic condylar lesion with or without pathologic fracture. Sometimes new bone formations are observed. The purpose of the article is to add new cases to the literatures.

  11. Eosinophilic granuloma of the mandibular condyle

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Kyung Hoe; Yi, Won Jin; Oh, Sung Won; Lee, Sam Sun [Department of Oral and Maxillofacial Radiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Choi, Mun Kyung [Department of Oral and Maxillofacial Surgery, College of Medicine, Inje University Sanggye Paik Hospital, Seoul (Korea, Republic of)

    2008-03-15

    The present study reports a case of eosinophilic granuloma of the mandibular condyle. Eosinophilic granulomas on the mandibular condyle are very rare, but there are several common clinical and radiographic presentations. The clinical presentations involve swelling on preauricular area, limitation of opening, TMJ pain, etc. The radiographic presentations involve radiolucent lytic condylar lesion with or without pathologic fracture. Sometimes new bone formations are observed. The purpose of the article is to add new cases to the literatures.

  12. Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.

    Science.gov (United States)

    Drake, Matthew G; Bivins-Smith, Elizabeth R; Proskocil, Becky J; Nie, Zhenying; Scott, Gregory D; Lee, James J; Lee, Nancy A; Fryer, Allison D; Jacoby, David B

    2016-09-01

    Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60-70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase-deficient transgenic mice, did not reduce eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.

  13. Evidence for eosinophil degranulation in acute appendicitis

    Directory of Open Access Journals (Sweden)

    Santosh G

    2008-04-01

    Full Text Available Finding of increased numbers of eosinophils in the muscle in cases of acute appendicitis has led to the hypothesis that it may have an allergic origin. This study aimed to measure the eosinophil degranulation resulting in a rise in the serum of eosinophil granule proteins that would be expected in such cases. The levels of serum eosinophil cationic protein (ECP measured by chemiluminescence assay in acute appendicitis were compared, with those of appropriate controls. Mean (95% CI serum ECP (µg/L levels were: acute appendicitis 45.3 (27.7-63.0; normal appendix 22.7 (16.0-29.3; asthma 24.2 (4.6-43.8; and healthy volunteers 13.2 (8.3-18.1. In cases of acute appendicitis, there is an inverse relationship between duration of symptoms and serum ECP. However, this was not statistically significant. Significant local eosinophil activation and degranulation occurs in acute appendicitis, enough to cause a rise in serum levels of eosinophil chemotactic protein

  14. Synthesis of pro-inflammatory cytokines and adhesion molecules expression by the irradiated human monocyte/macrophage

    International Nuclear Information System (INIS)

    Pons, I.

    1997-09-01

    As lesions induced by ionizing radiations are essentially noticed in organs the functional and structural organisation of which depend on the highly proliferative stem cell pool, the author reports an in-vivo investigation of the effect of a gamma irradiation on the expression and secretion of pro-inflammatory cytokines par human monocytes/macrophages. In order to study the role of the cell environment in the radiation-induced inflammation, the author studied whether a co-stimulation of monocytes/macrophages by gamma irradiation, or the exposure of co-cultures of monocytes/macrophages and lymphocytes, could modulate the regulation of inflammatory cytokines. The author also studied the modulation of the expression of adhesion molecules mainly expressed by the monocyte/macrophage, and the membrane density of the CD14 receptor after irradiation of monocytes/macrophages during 24 hours, and of totally differentiated macrophages after seven days of culture

  15. Eosinophilic Pancreatitis: A Rare Cause of Recurrent Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Jennifer Reppucci

    2017-03-01

    Full Text Available Eosinophilic pancreatitis is a rare form of recurrent acute pancreatitis that demonstrates distinct histologic features, including diffuse, periductal, acinar, and septal inflammatory infiltrates comprised of a pure or predominant population of eosinophils, eosinophilic phlebitis and arteritis, and localized eosinophilic infiltrates with pseudocyst formation. It is associated with elevated serum immunoglobulin E levels, an elevated eosinophil count with systemic manifestations, and eosinophilic infiltrates in other organs of the gastrointestinal tract. We present a case of eosinophilic pancreatitis in a 44-year-old man who was diagnosed after pancreatic resection for recurrent bouts of acute pancreatitis. While the gross and histologic evaluations matched other reported cases of eosinophilic pancreatitis, our patient had only minimal peripheral eosinophilia, no reported history of symptoms related to elevated eosinophilia or immunoglobulin E, and only mild eosinophilic infiltrates in his gallbladder.

  16. Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma

    NARCIS (Netherlands)

    Meijer, RJ; Postma, DS; Kauffman, HF; Arends, LR; Koeter, GH; Kerstjens, HAM

    Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response. Aim We

  17. Angiostrongylus cantonensis eosinophilic meningitis: a clinical study of 42 consecutive cases in French Polynesia.

    Science.gov (United States)

    Oehler, Erwan; Ghawche, Frédéric; Delattre, Alex; Berberian, Anthony; Levy, Marc; Valour, Florent

    2014-06-01

    In endemic areas, eosinophilic meningitis is mainly caused by Angiostrongylus cantonensis. We describe a series of this poorly-known condition. Retrospective cohort study (2000-2012) including all patients diagnosed with eosinophilic meningitis in French Polynesia. Forty-two patients (males: 61.9%, age: 22 (IQR 17-32)) were diagnosed with a serologically proven (n=13) or probable A. cantonensis meningitis, mostly during the dry season (66.6%) and following the consumption of or prolonged contact with an intermediate/paratenic host (64.3%). No differential diagnosis was found in probable cases, in whom serological tests were performed earlier (7.5 days (6.5-10)) compared to positive patients (7.5 (6.5-10) versus 11 (7-30) days, p=0.02). The most commonly reported symptom was headache (92.8%). Fever (7.1%) and biological inflammatory syndrome (14.3%) were rare. Blood eosinophil count was 1200/mm(3) (900-2548). Cerebrospinal fluid (CSF) analysis disclosed a protein level of 0.9 g/L (0.7-1.1), a CSF/plasma glucose ratio of 0.50 (0.40-0.55), and 500 leucocytes/mm(3) (292-725; eosinophils: 42.0% (29.5-60); lymphocytes: 46.5% (32.5-59.0)). Thirteen cases (31.0%) were severe, with 11 focal neurological deficits. A delayed hospital referral (OR 1.13, p=0.05) was associated with severity. A. cantonensis meningitis must be evocated in young patients with meningitic syndrome, severe headache, and CSF inflammation with predominance of eosinophils. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Eosinophilic Esophagitis: Relevance of Mast Cell Infiltration.

    Science.gov (United States)

    Strasser, Daniel S; Seger, Shanon; Bussmann, Christian; Pierlot, Gabin M; Groenen, Peter M A; Stalder, Anna K; Straumann, Alex

    2018-05-17

    Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease characterized clinically by symptoms of esophageal dysfunction and histopathologically by a prominent eosinophilic inflammation. Despite eosinophils having histologically a pre-dominant position, their role in the immunopathogenesis of the disease is still questionable. Several other inflammatory cells are involved and may play a critical role as well. The purpose of this study was to characterize the mast cell infiltration, and to correlate it with clinical state of EoE. Using immunohistochemistry and quantitative morphometry, we extensively investigated eosinophils and mast cells in esophageal biopsies from patients with active EoE and from patients with EoE in remission, and compared the findings with healthy individuals. In EoE, epithelium and lamina propria were similarly infiltrated with eosinophils. In contrast, mast cells infiltration was limited to the epithelium, displaying a localized immune response. Interestingly, whereas epithelial mast cells and eosinophils were high in active EoE, some patients in remission e.g. normalized epithelial eosinophils, showed remaining high numbers of mast cells. Patient clustering supported 2 groups of patients in clinical remission, differentiating based on presence or absence of epithelial mast cells. Active EoE is characterized - in addition to the well-known tissue eosinophilia by a marked epithelium-restricted mast cell infiltration. Of interest, in a subgroup of patients, mast cell infiltration persisted despite clinical remission. To elucidate the clinical consequence of persistent epithelial mast cells infiltration further studies are required following patients in clinical remission longitudinally. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

    Science.gov (United States)

    Hara, Tomoya; Yamaguchi, Koji; Iwase, Takashi; Kadota, Muneyuki; Bando, Mika; Ogasawara, Kozue; Bando, Sachiko; Ise, Takayuki; Niki, Toshiyuki; Ueda, Yuka; Tomita, Noriko; Taketani, Yoshio; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

    2013-01-01

    A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

  20. Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice

    International Nuclear Information System (INIS)

    Hiyoshi, Kyoko; Ichinose, Takamichi; Sadakane, Kaori; Takano, Hirohisa; Nishikawa, Masataka; Mori, Ikuko; Yanagisawa, Rie; Yoshida, Seiichi; Kumagai, Yoshito; Tomura, Shigeo; Shibamoto, Takayuki

    2005-01-01

    Asian sand dust (ASD) containing sulfate (SO 4 2- ) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO 4 2- toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO 4 2- (ASD-SO 4 ); OVA+ASD; OVA+ASD-SO 4 . ASD or ASD-SO 4 alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO 4 increased pro-inflammatory mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO 4 enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO 4 2- was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO 4 group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils

  1. New Insights into Eosinophilic Otitis Media.

    Science.gov (United States)

    Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

    2015-12-01

    Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM.

  2. GPNMB promotes proliferation of developing eosinophils.

    Science.gov (United States)

    Hwang, Sae Mi; Kang, Jin Hyun; Kim, Bo Kyum; Uhm, Tae Gi; Kim, Hye Jeong; Lee, Hyune-Hwan; Binas, Bert; Chung, Il Yup

    2017-08-01

    Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is expressed in a wide variety of cell types, including haematopoietic lineages. We previously demonstrated that GPNMB is one of the most highly expressed genes at an early and intermediate stage of eosinophil development. We herein examined GPNMB expression and its possible functional effect using cord blood (CB) CD34+ haematopoietic stem cells differentiating toward eosinophils during a 24-day culture period. Western blot and confocal microscopy analyses showed that GPNMB reached its highest levels at day 12 with most GPNMB-positive cells also expressing major basic protein 1 (MBP1), an eosinophil granule protein. GPNMB declined thereafter, but was still present at an appreciable level at day 24, the time when CB eosinophils most abundantly expressed MBP1 and were thus considered fully differentiated. When the developing CB cells were cultured in the presence of a blocking anti-GPNMB antibody, cell proliferation was significantly reduced. In agreement, ectopic expression of GPNMB in heterologous cells resulted in a significant increase in cell proliferation, while small interfering RNA of GPNMB inhibited the GPNMB-mediated proliferation. Thus, GPNMB is expressed in a temporal manner during eosinophil development and delivers a proliferative signal upon activation. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  3. Chronic eosinophilic pneumonia: CT findings

    International Nuclear Information System (INIS)

    Gutierrez, Haydee; Beccar Varela, Lucia; De Felippi, Maria S.

    2002-01-01

    Objective: To assess the usefulness of computerized tomography (CT) in the diagnosis of chronic eosinophilic pneumonia. Material and Methods: A double helical CT was performed in 6 patients referred to our center because of a chest X-ray with pulmonary infiltrates. Clinical presentation was cough, fever and eosinophilia in peripheral blood. Patients' age ranged from 25 to 55 years; 4 were women and 2 were men, one of the latter had a history of bronchial asthma. All patients received treatment with corticosteroids, with remission of the clinical and radiological parameters. Three patients underwent a control CT. Results: Findings consisted in focal parenchymal alterations, with areas of pulmonary consolidation and areas of 'ground glass' appearance; both patterns coexisted in certain areas. In 3 cases the lesions extended from the apices to the pulmonary bases, with predominance of the upper and middle fields. In 1 patient, there was frank predominance in the left hemi thorax. In another patient, who had a history of asthma, there were signs of pulmonary hyperinflation, with diffuse thickening of the bronchial walls, added to the previously mentioned findings, which involved the entire lung. In the mediastinum, 1 patient had lymph nodes larger than 1 cm, 3 had lymph nodes that were not enlarged but were more numerous than usual, and in the remaining patients no lymph nodes were found. The control CT's showed almost total resolution of the pulmonary infiltrates. Conclusion: The combination of eosinophilia and characteristic pulmonary infiltrates with a likely clinical presentation, associated with an optimal response to treatment with corticosteroids allows to make a reliable diagnosis and avoids the need for a pulmonary biopsy. (author)

  4. Roles and Regulation of Gastrointestinal Eosinophils in Immunity and Disease

    Science.gov (United States)

    Jung, YunJae; Rothenberg, Marc E.

    2014-01-01

    Eosinophils have been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergy reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system. PMID:25049430

  5. Molecular Mechanisms That Underlie the Dynamic Adaptation of Innate Monocyte Memory to Varying Stimulant Strength of TLR Ligands.

    Science.gov (United States)

    Yuan, Ruoxi; Geng, Shuo; Li, Liwu

    2016-01-01

    In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by super-low dose LPS exhibited higher levels of transcription factor, interferon regulatory factor 5 (IRF5), and reduced levels of transcriptional modulator B lymphocyte-induced maturation protein-1 (Blimp-1). Intriguingly, the inflammatory monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp contrast, rising doses of TLR3 agonist preferentially caused inflammatory adaptation without inducing tolerance. At the molecular level, the differential regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the understanding of monocyte adaptation and memory toward distinct TLR ligands.

  6. Esophageal trachealization: A feature of eosinophilic esophagitis

    International Nuclear Information System (INIS)

    AlHussaini, Abdulrahman A; Semaan, Toufic; ElHag, Imad A

    2009-01-01

    Eosinophilic esophagitis (EE) is an inflammatory condition characterized by intense eosinophilic infiltration of the esophagus. EE is frequently misdiagnosed as gastroesophageal reflux disease. Here, we present a child with EE and a characteristic endoscopic finding, r inged esophagus . An 11-year-old Saudi boy presented with dysphagia for 1 year. He had experienced an intermittent sensation of solid food sticking in his chest, which was relieved by drinking liquids. A barium swallow excluded anatomical causes of dysphagia, but revealed multiple-ringed esophagus. Endoscopy showed a furrowing and trachealizing appearance of the entire esophagus. Hisologically, extensive eosinophilic infiltration was a feature in biopsies obtained from the esophagus. The child responded well to a 2-month course of inhaled fluticasone. Symptoms recurred 3 months after discontinuation of therapy, which necessitated resumption of inhaled fluticasone. The endoscopic appearance of multiple esophageal rings should raise suspicion of EE and be confirmed by esophageal biopsies. (author)

  7. Impaired esophageal motor function in eosinophilic esophagitis

    Directory of Open Access Journals (Sweden)

    Cecilio Santander

    2015-10-01

    Full Text Available Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

  8. Impaired esophageal motor function in eosinophilic esophagitis.

    Science.gov (United States)

    Santander, Cecilio; Chavarría-Herbozo, Carlos M; Becerro-González, Irene; Burgos-Santamaría, Diego

    2015-10-01

    Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

  9. The potential implication of eosinophil activation in the pathogenesis ...

    African Journals Online (AJOL)

    Ehab

    The potential implication of eosinophil activation in the pathogenesis of childhood asthma. INTRODUCTION. Asthma is recognized as an eosinophil mediated inflammation of the airways1. Eosinophils are major contributors to the damage in the airways of asthmatic patients which when activated, degranulate and release ...

  10. EOSINOPHILS: MULTIFACETED BIOLOGIC PROPERTIES AND ROLES IN HEALTH AND DISEASE

    Science.gov (United States)

    Kita, Hirohito

    2011-01-01

    Summary Eosinophils are leukocytes resident in mucosal tissues. During Th2-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with pro-inflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field. PMID:21682744

  11. Eosinophils mediate protective immunity against secondary nematode infection.

    Science.gov (United States)

    Huang, Lu; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Luber, Kierstin L; Lee, Nancy A; Lee, James J; Appleton, Judith A

    2015-01-01

    Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode Trichinella spiralis, eosinophils play an important immune regulatory role that promotes larval growth and survival in skeletal muscle. In this study, we aimed to address the function of eosinophils in secondary infection with T. spiralis. By infecting eosinophil-ablated mice, we found that eosinophils are dispensable for immunity that clears adult worms or controls fecundity in secondary infection. In contrast, eosinophil ablation had a pronounced effect on secondary infection of skeletal muscle by migratory newborn larvae. Restoring eosinophils to previously infected, ablated mice caused them to limit muscle larvae burdens. Passive immunization of naive, ablated mice with sera or Ig from infected donors, together with transfer of eosinophils, served to limit the number of newborn larvae that migrated in tissue and colonized skeletal muscle. Results from these in vivo studies are consistent with earlier findings that eosinophils bind to larvae in the presence of Abs in vitro. Although our previous findings showed that eosinophils protect the parasite in primary infection, these new data show that eosinophils protect the host in secondary infection. Copyright © 2014 by The American Association of Immunologists, Inc.

  12. The radioactive labeling of monocytes

    International Nuclear Information System (INIS)

    Ensing, G.J.

    1985-01-01

    With the aim of studying a possible relationship between circulating monocytes and Sternberg-Reed cells investigations were started on the specific labeling of monocytes. In this thesis the literature on the pertinent data has been reviewed and a series of experiments on the monocyte labeling procedure has been described. The principles of cell labeling with radioactive compounds were discussed. 1. Total separation of the particular cell population to be labeled and subsequent labeling with a non-specific radiopharmaceutical. 2. Specific cell labeling in a mixture of cell types based on a well defined affinity of the cell under study for the radiopharmaceutical used. Next the radionuclides that can be used for cell labeling purposes were discussed with special attention for 111 In and its chelates. The principles of radiodosimetry were also discussed shortly. This section was focussed on the radiation dose the labeled cells receive because of the intracellular localized radioactivity. The radiation burden is high in comparison to amounts of radiation known to affect cell viability. A newly developed method for labeling monocytes specifically by phagocytosis of 111 In-Fe-colloid without apparent loss of cells was described in detail. (Auth.)

  13. Characterization of a receptor for interleukin-5 on human eosinophils and the myeloid leukemia line HL-60

    International Nuclear Information System (INIS)

    Ingley, E.; Young, I.G.

    1991-01-01

    Interleukin-5 (IL-5) promotes the growth and differentiation of human eosinophils and may regulate the selective eosinophilia and eosinophil activation seen in certain diseases. Radiolabeled recombinant human IL-5 (hIL-5) was used to characterize the IL-5 receptor present on normal human eosinophils and on the myeloid leukemia line HL-60, which can be induced to differentiate into eosinophilic cells. Binding studies with eosinophils and HL-60 cells grown under alkaline conditions demonstrated similar high-affinity binding sites for hIL-5 on both cell types with kd values of approximately 400 pmol/L. The binding observed was specific in that it was not inhibited by hIL-3, human granulocyte-macrophage colony-stimulating factor, or hIL-2. Binding studies with a number of other human cell lines, including a B-lymphoma line, and with lymphocyte and neutrophil preparations were also performed, but IL-5 receptors were not detectable on these cells. The number of hIL-5 receptors on HL-60 cells could be correlated with its propensity to differentiate towards an eosinophilic cell type. Expression of hIL-5 receptors on HL-60 cells was upregulated by butyric acid under alkaline conditions, downregulated by hIL-3, virtually eliminated by dimethyl sulfoxide and hIL-5, while hIL-2 had no detectable effect. One major 125I-hIL-5-crosslinked complex of 75 to 85 Kd in Mr was detected on HL-60 cells using crosslinking agents giving a molecular mass of 55 to 60 Kd for the hIL-5 receptor itself. Studies using cellular autoradiography showed that IL-5 receptors were evenly distributed on eosinophils but that receptor distribution on HL-60 cells was noticeably heterogeneous. Eosinophils were the only cells in slides prepared from peripheral blood that had detectable levels of IL-5 receptors in agreement with the specific action of IL-5 on the human eosinophil lineage

  14. Transcriptome Analysis of Circulating Immune Cell Subsets Highlight the Role of Monocytes in Zaire Ebola Virus Makona Pathogenesis

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    Andrea R. Menicucci

    2017-10-01

    Full Text Available Existing models of Ebola virus disease (EVD suggest antigen-presenting cells are initial targets of Zaire ebolavirus (ZEBOV. In vitro studies have shown that ZEBOV infection of monocytes and macrophages results in the production of inflammatory mediators, which may cause lymphocyte apoptosis. However, these findings have not been corroborated by in vivo studies. In this study, we report the first longitudinal analysis of transcriptional changes in purified monocytes, T-cells, and B-cells isolated from cynomolgus macaques following infection with ZEBOV-Makona. Our data reveal monocytes as one of the major immune cell subsets that supports ZEBOV replication in vivo. In addition, we report a marked increase in the transcription of genes involved in inflammation, coagulation, and vascular disease within monocytes, suggesting that monocytes contribute to EVD manifestations. Further, genes important for antigen presentation and regulation of immunity were downregulated, potentially subverting development of adaptive immunity. In contrast, lymphocytes, which do not support ZEBOV replication, showed transcriptional changes limited to a small number of interferon-stimulated genes (ISGs and a failure to upregulate genes associated with an antiviral effector immune response. Collectively, these data suggest that ZEBOV-infected monocytes play a significant role in ZEBOV-Makona pathogenesis and strategies to suppress virus replication or modify innate responses to infection in these cells should be a priority for therapeutic intervention.

  15. The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells.

    Science.gov (United States)

    Lee, Ji-Sook; Yang, Eun Ju; Kim, In Sik

    2009-12-01

    Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.

  16. Studies on the mechanism of endogenous pyrogen production. III. Human blood monocytes.

    Science.gov (United States)

    Bodel, P

    1974-10-01

    The characteristics of pyrogen production and release by human blood monocytes were investigated. A dose-response assay of monocyte pyrogen in rabbits indicated a linear relationship of temperature elevation to dose of pyrogen at lower doses. Monocytes did not contain pyrogen when first obtained, nor did they release it spontaneously even after 5 days of incubation in vitro. Pyrogen production was apparent 4 h after stimulation by endotoxin or phagocytosis, and continued for 24 h or more. Puromycin, an inhibitor of protein synthesis, prevented both initiation and continuation of pyrogen production and release. Pyrogen-containing supernates retained most pyrogenic activity during overnight incubation even in the presence of activated cells. Lymphocytes appeared to play no role in either initiation or continuation of pyrogen production in these studies.

  17. Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors.

    Science.gov (United States)

    Ishihara, Kenji; Takahashi, Aki; Kaneko, Motoko; Sugeno, Hiroki; Hirasawa, Noriyasu; Hong, JangJa; Zee, OkPyo; Ohuchi, Kazuo

    2007-03-06

    EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and H3, inhibited the proliferation of EoL-1 cells without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta7, CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of histones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils.

  18. Eosinophils in vasculitis: characteristics and roles in pathogenesis

    Science.gov (United States)

    Khoury, Paneez; Grayson, Peter C.; Klion, Amy D.

    2016-01-01

    Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides. PMID:25003763

  19. Production of monoclonal antibodies reactive with ovine eosinophils

    Directory of Open Access Journals (Sweden)

    Meeusen Els NT

    2007-09-01

    Full Text Available Abstract Background There is strong evidence implicating eosinophils in host defence against parasites as well as allergic disease pathologies. However, a lack of reagents such as monoclonal antibodies (mAbs specific for eosinophils has made it difficult to confirm the functional role of eosinophils in such disease conditions. Using an established mammary model of allergic inflammation in sheep, large numbers of inflammatory cells enriched for eosinophils were collected from parasite-stimulated mammary glands and used for the generation of mAbs against ovine eosinophils. Results A panel of mAbs was raised against ovine eosinophils of which two were shown to be highly specific for eosinophils. The reactivity of mAbs 3.252 and 1.2 identified eosinophils from various cell and tissue preparations with no detectable reactivity on cells of myeloid or lymphoid lineage, tissue mast cells, dendritic cells, epithelial cells or other connective tissues. Two other mAbs generated in this study (mAbs 4.4 and 4.10 were found to have reactivity for both eosinophils and neutrophils. Conclusion This study describes the production of new reagents to identify eosinophils (as well as granulocytes in sheep that will be useful in studying the role of eosinophils in disease pathologies in parasite and allergy models.

  20. Eosinophilic granulomatosis with polyangiitis: an overview

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    Andrea eGioffredi

    2014-11-01

    Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA is a multisystemic disorder, belonging to the small vessel ANCA-associated vasculitis, defined as a eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium-sized vessels, associated with asthma and eosinophilia. EGPA pathogenesis is not well known: HLA-DRB1*04 and *07, HLA-DRB4 and IL10.2 haplotype of the IL-10 promoter gene are the most studied genetic determinants. Among the acquired pathogenetic factors, the exposure to different allergens, infections, vaccinations, drugs and silica exposure have been involved.Eosinophils are the most characteristic cells in EGPA and different studies have demonstrated their role as effector and immunoregulatory cells.EGPA is considered a disease with a prevalent activation of the Th2 cellular-mediated inflammatory response but also humoral immunity plays an important role. A link between B and T inflammatory responses may explain different disease features. EGPA typically develops into three sequential phases: the allergic phase, distinguished by the occurrence of asthma, allergic rhinitis and sinusitis, the eosinophilic phase, in which the main pathological finding is the eosinophilic organ infiltrations (e.g. lungs, heart and gastrointestinal system and the vasculitic phase, characterized by purpura, peripheral neuropathy and constitutional symptoms.ANCA (especially pANCA anti-MPO are present in 40-60% of the patients. An elevation of IgG4 is frequently found. Corticosteroids and cyclophosphamide are classically used for remission induction, while azathioprine and methotrexate are the therapeutic options for remission maintenance. B-cell depletion with rituximab has shown promising results for remission induction.

  1. The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

    Directory of Open Access Journals (Sweden)

    Pedro Xavier-Elsas

    2015-01-01

    Full Text Available Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp- deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

  2. Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission

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    Yanping Tong

    2018-02-01

    Full Text Available BackgroundA prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS. Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3 and CCL13 [monocyte chemoattractant protein (MCP-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26 and MCPs (CCL13, CCL2, CCL8, and CCL7 in patients with NMOSD during remission.MethodsHealthy controls (HC; n = 30 and patients with MS (n = 47 and NMOSD (n = 58 in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF-α, and interleukin (IL-1β levels were detected using the human cytokine multiplex assay.ResultsPlasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1β, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD.ConclusionThe study indicates that in NMOSD, the overproduction of cytokines such as IL-1β and TNF-α during remission stimulates eosinophilic chemoattractants such as

  3. External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.

    Science.gov (United States)

    Wagener, A H; de Nijs, S B; Lutter, R; Sousa, A R; Weersink, E J M; Bel, E H; Sterk, P J

    2015-02-01

    Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation. Quantifying the mutual relationships of blood eosinophils, FE(NO), and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma. The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FENO were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC). In the external validation cohort, ROC AUC for blood eosinophils was 89% (peosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, peosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma. NTR1846 and NTR2364. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Delivery of TLR7 agonist to monocytes and dendritic cells by DCIR targeted liposomes induces robust production of anti-cancer cytokines

    DEFF Research Database (Denmark)

    Klauber, Thomas Christopher Bogh; Laursen, Janne Marie; Zucker, Daniel

    2017-01-01

    Tumor immune escape is today recognized as an important cancer hallmark and is therefore a major focus area in cancer therapy. Monocytes and dendritic cells (DCs), which are central to creating a robust anti-tumor immune response and establishing an anti-tumorigenic microenvironment, are directly...... targeted by the tumor escape mechanisms to develop immunosuppressive phenotypes. Providing activated monocytes and DCs to the tumor tissue is therefore an attractive way to break the tumor-derived immune suppression and reinstate cancer immune surveillance. To activate monocytes and DCs with high...... as their immune activating potential in blood-derived monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs). Monocytes and mDCs were targeted with high specificity over lymphocytes, and exhibited potent TLR7-specific secretion of the anti-cancer cytokines IL-12p70, IFN-α 2a, and IFN-γ. This delivery system...

  5. Human eosinophils constitutively express a unique serine protease, PRSS33.

    Science.gov (United States)

    Toyama, Sumika; Okada, Naoko; Matsuda, Akio; Morita, Hideaki; Saito, Hirohisa; Fujisawa, Takao; Nakae, Susumu; Karasuyama, Hajime; Matsumoto, Kenji

    2017-07-01

    Eosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis. Human eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads. Protease/proteinase expression in eosinophils and release into the supernatant were evaluated by microarray analysis, qPCR, ELISA, flow cytometry and immunofluorescence staining before and after stimulation with eosinophil-activating cytokines and secretagogues. mRNAs for extracellular matrix proteins in human normal fibroblasts were measured by qPCR after exposure to recombinant protease serine 33 (PRSS33) protein (rPRSS33), created with a baculovirus system. Human eosinophils expressed relatively high levels of mRNA for metalloproteinase 25 (MMP25), a disintegrin and metalloprotease 8 (ADAM8), ADAM10, ADAM19 and PRSS33. Expression of PRSS33 was the highest and eosinophil-specific. PRSS33 mRNA expression was not affected by eosinophil-activating cytokines. Immunofluorescence staining showed that PRSS33 was co-localized with an eosinophil granule protein. PRSS33 was not detected in the culture supernatant of eosinophils even after stimulation with secretagogues, but its cell surface expression was increased. rPRSS33 stimulation of human fibroblasts increased expression of collagen and fibronectin mRNAs, at least in part via protease-activated receptor-2 activation. Activated eosinophils may induce fibroblast extracellular matrix protein synthesis via cell surface expression of PRSS33, which would at least partly explain eosinophils' role(s) in airway remodeling. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier

  6. Heterogeneity of Bovine Peripheral Blood Monocytes

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    Jamal Hussen

    2017-12-01

    Full Text Available Peripheral blood monocytes of several species can be divided into different subpopulations with distinct phenotypic and functional properties. Herein, we aim at reviewing published work regarding the heterogeneity of the recently characterized bovine monocyte subsets. As the heterogeneity of human blood monocytes was widely studied and reviewed, this work focuses on comparing bovine monocyte subsets with their human counterparts regarding their phenotype, adhesion and migration properties, inflammatory and antimicrobial functions, and their ability to interact with neutrophilic granulocytes. In addition, the differentiation of monocyte subsets into functionally polarized macrophages is discussed. Regarding phenotype and distribution in blood, bovine monocyte subsets share similarities with their human counterparts. However, many functional differences exist between monocyte subsets from the two species. In contrast to their pro-inflammatory functions in human, bovine non-classical monocytes show the lowest phagocytosis and reactive oxygen species generation capacity, an absent ability to produce the pro-inflammatory cytokine IL-1β after inflammasome activation, and do not have a role in the early recruitment of neutrophils into inflamed tissues. Classical and intermediate monocytes of both species also differ in their response toward major monocyte-attracting chemokines (CCL2 and CCL5 and neutrophil degranulation products (DGP in vitro. Such differences between homologous monocyte subsets also extend to the development of monocyte-derived macrophages under the influence of chemokines like CCL5 and neutrophil DGP. Whereas the latter induce the differentiation of M1-polarized macrophages in human, bovine monocyte-derived macrophages develop a mixed M1/M2 macrophage phenotype. Although only a few bovine clinical trials analyzed the correlation between changes in monocyte composition and disease, they suggest that functional differences between

  7. Chronic lymphocytic leukemia (CLL)

    Science.gov (United States)

    ... is used for painful and enlarged lymph nodes. Blood transfusions or platelet transfusions may be required if blood ... unexplained fatigue, bruising, excessive sweating, or weight loss. Alternative ... Leukemia - chronic lymphocytic (CLL); Blood cancer - chronic lymphocytic leukemia; Bone marrow cancer - chronic ...

  8. Culicoides antigen extract stimulates equine blood mononuclear (BMN) cell proliferation and the release of eosinophil adherence-inducing factor(s).

    Science.gov (United States)

    Mckelvie, J; Foster, A P; Hamblin, A S; Cunningham, F M

    2001-04-01

    Intradermal injection of a Culicoides antigen extract (CAgX) induces T lymphocyte and eosinophil accumulation in the skin of horses with sweet itch. Blood mononuclear (BMN) cells from normal ponies proliferate when stimulated by mitogen (phytohaemagglutinin, PHA) or antigen (tetanus toxoid, TT) and, as shown here, release soluble factor(s) that induce eosinophil adherence. CAgX also caused concentration dependent proliferation of BMN cells from sweet itch and normal ponies [stimulation index: 29 (13) and 17 (7) for BMN cells from sweet itch and normal ponies, respectively during the active phase of disease; 4 microg protein ml(-1)CAgX; 168 h]. A heat labile factor(s) which caused eosinophil adherence was also released [sweet itch ponies: 6.0 (1.6) per cent adherence versus 1.3 (0.4) per cent; normal ponies: 6.6 (0.5) per cent adherence versus 0.9 (0.1) per cent for supernatants from CAgX (4 microg protein ml(-1); 48 hours) stimulated versus unstimulated BMN cells, respectively]. These results suggest that soluble proteins released from T lymphocytes could affect eosinophil function in the lesional skin of sweet itch horses. Copyright 2001 Harcourt Publishers Ltd.

  9. Eosinophilic Esophagitis in Brazilian Pediatric Patients

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    Mayra Isabel Correia Pinheiro

    2013-01-01

    Full Text Available We examined 11 pediatric patients with eosinophilic esophagitis with a tardy diagnosis. The symptoms were initially thought to be related to other diseases, leading to the use of inadequate therapeutic approaches. The patients were between 3 and 17 years old (mean 7.8 ± 3.8 years, and 8 of the patients were male. Common symptoms included abdominal pain, regurgitation, difficulty in gaining weight, vomiting, dysphagia, and coughing. The mean age for the onset of symptoms was 4.3 ± 2.9 years. Endoscopic findings included normal mucosa in five (45% patients, thickening of the mucosa with longitudinal grooves in three (27%, erosive esophagitis in two (18%, and a whitish stippling in one (9% patient. Treatment included the use of a topical corticosteroid for 10 patients. In eight (73% cases, the treatment made the symptoms disappear. Ten patients underwent histopathological management after treatment, with a decrease in the number of eosinophils.

  10. [Eosinophilic esophagitis, a pathology on the rise].

    Science.gov (United States)

    Miranda García, M; Gutiérrez Teira, B

    2013-10-01

    The eosinophilic esofagitis is a pathology that consists of an inflammatory condition of the esophagus, which is characterized for having a high percentage of eosinophils. It is a problem of allergic origin and his diagnosis is increasing in the population, especially in children and adult young persons, throughout last decade. The fisiopathology is not completely established nowadays. The diagnosis is confirmed with endoscopia and capture of biopsies. The differential diagnosis is necessary to be done with the disease for reflux gastroesofágico, gastroenteritis eosinofílica, by Crohn's disease, pathology of connective fabric, syndrome hipereosinofílico, infections and response of hypersensitivity to medicaments. Nowadays there is no a treatment that is definitive. We present a clinical case, which was valued initially for the consultation of Primary care. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  11. Humoral immunity provides resident intestinal eosinophils access to luminal antigen via eosinophil-expressed low affinity Fc gamma receptors

    Science.gov (United States)

    Smith, Kalmia M.; Rahman, Raiann S.; Spencer, Lisa A.

    2016-01-01

    Eosinophils are native to the healthy gastrointestinal tract, and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g. food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct antigen engagement elicits eosinophil effector functions including degranulation and antigen presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food antigens by a columnar epithelium might similarly engage food antigens. Using an intestinal ligated loop model in mice, here we determined that resident intestinal eosinophils acquire antigen from the lumen of antigen-sensitized but not naïve mice in vivo. Antigen acquisition was immunoglobulin-dependent; intestinal eosinophils were unable to acquire antigen in sensitized immunoglobulin-deficient mice, and passive immunization with immune serum or antigen-specific IgG was sufficient to enable intestinal eosinophils in otherwise naïve mice to acquire antigen in vivo. Intestinal eosinophils expressed low affinity IgG receptors, and the activating receptor FcγRIII was necessary for immunoglobulin-mediated acquisition of antigens by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food antigens in sensitized mice via FcγRIII antigen focusing, and may therefore participate in antigen-driven secondary immune responses to oral antigens. PMID:27683752

  12. Eosinophilic Angiocentric Fibrosis of the Nasal Septum

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    Yunchuan Li

    2013-01-01

    Full Text Available Background. Eosinophilic angiocentric fibrosis (EAF is a rare benign condition of unknown aetiology that causes stenosis of the upper respiratory tract. It is most commonly found at the nasal septum and sinus mucosa causing mucosal thickening and nasal obstructive symptoms. The diagnosis is mainly based on characteristic histologic findings. Case Report. A 27-year-old young woman presented with a slow growing mass at her anterior nasal septum for over eight years. She complained of persistent nasal obstruction, epistaxis, sometimes diffused facial pain, and chronic headache. 3 years ago, the tumor was partially resected for ventilation and a nasal septum perforation was left. Imaging findings indicated soft-tissue thickening of the anterior part of septum and adjacent lateral nasal walls. Pathological examination showed numerous inflammatory cells infiltrates containing eosinophils, fibroinflammatory lesion with a whorled appearance fibrosis which typically surrounded vessels. A diagnosis of eosinophilic angiocentric fibrosis was made. All laboratory tests were unremarkable. Skin prick test was positive. The tumor-like lesion was totally resected. Conclusions. EAF is a rare benign and progressive disorder causing destruction. Combined with radiological imaging of EAF historical findings contribute to the diagnosis. It is important to prevent tumor from recurrence by total resection of the lesion.

  13. Canine Oral Eosinophilic Granuloma Treated with Electrochemotherapy

    Directory of Open Access Journals (Sweden)

    Matías Nicolás Tellado

    2014-01-01

    Full Text Available A case of a canine oral eosinophilic granuloma in a 14-year-old female crossbred is described. The dog was presented with a history of ptyalism, halitosis, local pain, decreased appetite, and blood staining noted on food and water bowls. Clinical, hematologic, and biochemical examinations, abdominal ultrasonography, and 3-view chest radiographs were performed, and no metastases were found. Histopathologic examination of two 6 mm punch biopsies from the oral lesion revealed the presence of eosinophilic granulomatous lesions in the submucosa. After treatment with corticosteroids and wide spectrum antibiotics no significant changes in clinical signs and lesion size were observed. Electrochemotherapy (ECT, a novel tumor treatment routinely used for cutaneous and subcutaneous tumors in human patients in the European Union since 2006, was used to treat the eosinophilic granuloma. The procedure was performed under general anesthesia, followed by intravenous administration of bleomycin. Six weeks after treatment a complete response with disappearance of the mass and improvement of clinical signs were observed.

  14. MR findings of calvarial eosinophilic granuloma

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    Choi, Gi Bok; Son, Seok Hyun; Eun, Choong Ki; Park, Sung Kun; Han, Sang Suk [Pusan Paik Hospital, Inje Univ., Pusan (Korea, Republic of); Choi, Sun Seob [Donga Univ. College of Medicine, Pusan (Korea, Republic of); Kim, Seong Min [Kosin Univ. College of Medicine, Pusan (Korea, Republic of); Kim, Chang Soo [Maryknoll Hospital, Pusan (Korea, Republic of)

    2001-03-01

    The purpose of this study was to evaluate the MR findings of calvarial eosinophilic granuloma. We reviewed the MR imaging studies of nine patients [M:F=3:6, aged 6-35 (mean, 20.5) years] with pathologically proven eosinophilic granuloma in the calvaria. The findings were evaluated for involvement of the diploic space, changes in adjacent bone marrow, distinction of the transitional zone, pattern of bone destruction, signal intensity and contrast enhancement of the tumor, and contrast enhancement of the adjacent dura. All lesions involved the diploic space, showed no change in adjacent bone marrow, and had a distinct transitional zone. In most (8/9) cases there was asymmetric bony destruction. On T1-weighted images, signal intensities of the tumors varied, while on T2-weighted images, hyperintensity was observed in seven cases, isointensity in one, and hypointensity in one. After the administration of contrast material, enhancement was homogeneous in four cases and inhomogeneous in five. Enhancement of the adjacent dura was demonstrated in all nine cases. The characteristic MR findings of calvarial eosinophilic granuloma are variable signal intensity on T1WI, high signal intensity on T2WI, and marked contrast enhancement; in addition, there is a distinct transitional zone, asymmetrical bony destruction, and associated dural enhancement.

  15. Blood eosinophil levels as a biomarker in COPD.

    Science.gov (United States)

    Brusselle, Guy; Pavord, Ian D; Landis, Sarah; Pascoe, Steven; Lettis, Sally; Morjaria, Nikhil; Barnes, Neil; Hilton, Emma

    2018-05-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder and patients respond differently to treatment. Blood eosinophils are a potential biomarker to stratify patient subsets for COPD therapy. We reviewed the value of blood eosinophils in predicting exacerbation risk and response to corticosteroid treatment in the available literature (PubMed articles in English; keywords: "COPD" and "eosinophil"; published prior to May 2017). Overall, clinical data suggest that in patients with a history of COPD exacerbations, a higher blood eosinophil count predicts an increased risk of future exacerbations and is associated with improved response to treatment with inhaled corticosteroids (in combination with long-acting bronchodilator[s]). Blood eosinophils are therefore a promising biomarker for phenotyping patients with COPD, although prospective studies are needed to assess blood eosinophils as a biomarker of corticosteroid response for this. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4+ and CD8+ T cells with a T-helper 1 profile

    Science.gov (United States)

    Garro, Ana P; Chiapello, Laura S; Baronetti, José L; Masih, Diana T

    2011-01-01

    Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, revealing a strong granulomatous response and a low susceptibility to dissemination. Moreover, it has been shown that eosinophils are components of the inflammatory response to C. neoformans infections. In this in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C. neoformans, and that the phenomenon involves the engagement of FcγRII and CD18. Moreover, our results showed that the phagocytosis of opsonized C. neoformans triggers eosinophil activation, as indicated by (i) the up-regulation of major histocompatibility complex (MHC) class I, MHC class II and costimulatory molecules, and (ii) an increase in interleukin (IL)-12, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production. However, nitric oxide (NO) and hydrogen peroxide (H2O2) synthesis by eosinophils was down-regulated after interaction with C. neoformans. Furthermore, this work demonstrated that CD4+ and CD8+ T lymphocytes isolated from spleens of infected rats and cultured with C. neoformans-pulsed eosinophils proliferate in an MHC class II- and class I-dependent manner, respectively, and produce important amounts of T-helper 1 (Th1) type cytokines, such as TNF-α and IFN-γ, in the absence of T-helper 2 (Th2) cytokine synthesis. In summary, the present study demonstrates that eosinophils act as fungal antigen-presenting cells and suggests that C. neoformans-loaded eosinophils might participate in the adaptive immune response. PMID:21039463

  17. A Non-Frequently Considered Diagnosis of Dysphagia; Eosinophilic Esophagitis

    OpenAIRE

    Mehmet Ağın; Nilgün Uyduran Ünal; Serdar İskit

    2015-01-01

    Eosinophilic Esophagitis is infiltration of esophagus mucosa by eosinophil leucocyte. It is rarely observed in children and the symptoms are similar to gastroesophageal reflux. This case, which was applied esophagus balloon dilatation in the pediatric surgery due to dysphagia and diagnosed eosinophilic esophagitis, was presented in order to attract attention to the approach to the child with dysphagia. Total IgE=834 IU/mL and specific IgE (-), Fx5 (-) was found negative. In ...

  18. Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

    Science.gov (United States)

    Odemuyiwa, Solomon O; Ilarraza, Ramses; Davoine, Francis; Logan, Michael R; Shayeganpour, Anooshirvan; Wu, Yingqi; Majaesic, Carina; Adamko, Darryl J; Moqbel, Redwan; Lacy, Paige

    2015-04-01

    Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin-dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT-PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet-activating factor, and secretory IgA-Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock-down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin-4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist-induced degranulation. © 2014 John Wiley & Sons Ltd.

  19. CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection.

    Science.gov (United States)

    van den Bosch, Thierry P P; Caliskan, Kadir; Kraaij, Marina D; Constantinescu, Alina A; Manintveld, Olivier C; Leenen, Pieter J M; von der Thüsen, Jan H; Clahsen-van Groningen, Marian C; Baan, Carla C; Rowshani, Ajda T

    2017-01-01

    During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during rejection. Here, we aimed to define and correlate monocyte-macrophage endomyocardial tissue profiles obtained at rejection and time points prior to rejection, with corresponding serial blood samples in 25 heart transplant recipients experiencing acute cellular rejection. Additionally, 33 healthy individuals served as control. Using histology, immunohistochemistry, confocal laser scan microscopy, and digital imaging expression of CD14, CD16, CD56, CD68, CD80, and CD163 were explored to define monocyte and macrophage tissue profiles during rejection. Fibrosis was investigated using Sirius Red stainings of rejection, non-rejection, and 1-year biopsies. Expression of co-stimulatory and migration-related molecules on circulating monocytes, and production potential for pro- and anti-inflammatory cytokines were studied using flow cytometry. At tissue level, striking CD16+ monocyte infiltration was observed during rejection ( p  rejection compared to barely present CD68+CD80+ M1 macrophages. Rejection was associated with severe fibrosis in 1-year biopsies ( p  rejection status, decreased frequencies of circulating CD16+ monocytes were found in patients compared to healthy individuals. Rejection was reflected by significantly increased CD54 and HLA-DR expression on CD16+ monocytes with retained cytokine production potential. CD16+ monocytes and M2 macrophages hallmark the correlates of heart transplant acute cellular rejection on tissue level and seem to be associated with fibrosis in the long term.

  20. World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management.

    Science.gov (United States)

    Gotlib, Jason

    2017-11-01

    The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm 3 and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder. Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes which includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2," and the "MPN subtype, chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion. The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g., watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES. Hydroxyurea and interferon-alpha have demonstrated efficacy as initial treatment and steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used

  1. Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract.

    Science.gov (United States)

    Hurrell, Jennifer M; Genta, Robert M; Melton, Shelby D

    2011-09-01

    Eosinophils, a constitutive component of the columnar-lined gastrointestinal tract, play an essential role in allergic responses and parasitic infections. The tissue density of these cells also increases in a variety of conditions of uncertain etiology. With the exception of the esophageal squamous epithelium, in which no eosinophils are normally present, the population of normal eosinophils in the remainder of the luminal gut is poorly defined. Therefore, histopathologists must rely on their subjective judgment to determine when a diagnosis of eosinophilic gastritis, enteritis, or colitis should be rendered. Eosinophilic esophagitis is currently the best defined and most studied eosinophilic condition of the digestive tract; therefore, the confidence in accurate diagnosis is increasing. In contrast, the characteristic clinicopathologic features of eosinophilic conditions affecting other parts of the digestive tract remain somewhat elusive. This review was designed to present pathologists with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis, gastritis, enteritis, and colitis. It was prepared by critically reviewing more than 200 articles on the topic, along with incorporating evidence accumulated through our own collective experience. We anticipate that by increasing pathologists' confidence in reporting these abnormal but often nameless eosinophilic infiltrates, we can help better define and characterize their significance.

  2. Radiation effects on lymphocytes

    International Nuclear Information System (INIS)

    Roser, B.

    1976-01-01

    This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

  3. Age Increases Monocyte Adhesion on Collagen

    Science.gov (United States)

    Khalaji, Samira; Zondler, Lisa; Kleinjan, Fenneke; Nolte, Ulla; Mulaw, Medhanie A.; Danzer, Karin M.; Weishaupt, Jochen H.; Gottschalk, Kay-E.

    2017-05-01

    Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin αx showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin αxβ2. Surprisingly, we find no significant age-dependent difference in gene expression of integrin αx or integrin β2. However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.

  4. Intermediate Monocytes but Not TIE2-Expressing Monocytes Are a Sensitive Diagnostic Indicator for Colorectal Cancer

    Science.gov (United States)

    Schauer, Dominic; Starlinger, Patrick; Reiter, Christian; Jahn, Nikolaus; Zajc, Philipp; Buchberger, Elisabeth; Bachleitner-Hofmann, Thomas; Bergmann, Michael; Stift, Anton; Gruenberger, Thomas; Brostjan, Christine

    2012-01-01

    We have conducted the first study to determine the diagnostic potential of the CD14++CD16+ intermediate monocytes as compared to the pro-angiogenic subset of CD14++CD16+TIE2+ TIE2-expressing monocytes (TEMs) in cancer. These monocyte populations were investigated by flow cytometry in healthy volunteers (N = 32) and in colorectal carcinoma patients with localized (N = 24) or metastatic (N = 37) disease. We further determined blood levels of cytokines associated with monocyte regulation. The results revealed the intermediate monocyte subset to be significantly elevated in colorectal cancer patients and to show the highest frequencies in localized disease. Multivariate regression analysis identified intermediate monocytes as a significant independent variable in cancer prediction. With a cut-off value at 0.37% (intermediate monocytes of total leukocytes) the diagnostic sensitivity and specificity ranged at 69% and 81%, respectively. In contrast, TEM levels were elevated in localized cancer but did not differ significantly between groups and none of the cytokines correlated with monocyte subpopulations. Of interest, in vitro analyses supported the observation that intermediate monocytes were more potently induced by primary as opposed to metastatic cancer cells which may relate to the immunosuppressive milieu established in the advanced stage of metastatic disease. In conclusion, intermediate monocytes as compared to TIE2-expressing monocytes are a more sensitive diagnostic indicator of colorectal cancer. PMID:22973451

  5. Intermediate monocytes but not TIE2-expressing monocytes are a sensitive diagnostic indicator for colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Dominic Schauer

    Full Text Available We have conducted the first study to determine the diagnostic potential of the CD14++CD16+ intermediate monocytes as compared to the pro-angiogenic subset of CD14++CD16+TIE2+ TIE2-expressing monocytes (TEMs in cancer. These monocyte populations were investigated by flow cytometry in healthy volunteers (N = 32 and in colorectal carcinoma patients with localized (N = 24 or metastatic (N = 37 disease. We further determined blood levels of cytokines associated with monocyte regulation. The results revealed the intermediate monocyte subset to be significantly elevated in colorectal cancer patients and to show the highest frequencies in localized disease. Multivariate regression analysis identified intermediate monocytes as a significant independent variable in cancer prediction. With a cut-off value at 0.37% (intermediate monocytes of total leukocytes the diagnostic sensitivity and specificity ranged at 69% and 81%, respectively. In contrast, TEM levels were elevated in localized cancer but did not differ significantly between groups and none of the cytokines correlated with monocyte subpopulations. Of interest, in vitro analyses supported the observation that intermediate monocytes were more potently induced by primary as opposed to metastatic cancer cells which may relate to the immunosuppressive milieu established in the advanced stage of metastatic disease. In conclusion, intermediate monocytes as compared to TIE2-expressing monocytes are a more sensitive diagnostic indicator of colorectal cancer.

  6. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults

    Directory of Open Access Journals (Sweden)

    Trautwein Christian

    2010-06-01

    Full Text Available Abstract Background Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during ageing, potentially influencing their functionality and contributing to immunosenescence. Results Circulating monocyte subsets, surface marker and chemokine receptor expression were analyzed in 181 healthy volunteers (median age 42, range 18-88. Unlike the unaffected total leukocyte or total monocyte counts, non-classical CD14+CD16+ monocytes significantly increased with age, but displayed reduced HLA-DR and CX3CR1 surface expression in the elderly. Classical CD14++CD16- monocyte counts did not vary dependent on age. Serum MCP-1 (CCL2, but not MIP1α (CCL3, MIP1β (CCL4 or fractalkine (CX3CL1 concentrations increased with age. Monocyte-derived macrophages from old or young individuals did not differ with respect to cytokine release in vitro at steady state or upon LPS stimulation. Conclusions Our study demonstrates dynamic changes of circulating monocytes during ageing in humans. The expansion of the non-classical CD14+CD16+ subtype, alterations of surface protein and chemokine receptor expression as well as circulating monocyte-related chemokines possibly contribute to the preserved functionality of the monocyte pool throughout adulthood.

  7. Efficient clinical-scale enrichment of lymphocytes for use in adoptive immunotherapy using a modified counterflow centrifugal elutriation program.

    Science.gov (United States)

    Powell, Daniel J; Brennan, Andrea L; Zheng, Zhaohui; Huynh, Hong; Cotte, Julio; Levine, Bruce L

    2009-01-01

    Clinical-scale lymphocyte enrichment from a leukapheresis product has been performed most routinely using costly magnetic bead separation systems that deplete monocytes, but this procedure may leave behind residual beads or antibodies in the enriched cell product. Counterflow centrifugal elutriation has been demonstrated previously to enrich monocytes efficiently for generation of dendritic cells. This study describes a modified elutriation procedure for efficient bead-free economical enrichment of lymphocytes from leukapheresis products from healthy donors and study subjects with human immunodeficiency virus (HIV) infection or malignancy. Modified program settings and conditions for the CaridianBCT Elutra device were investigated to optimize lymphocyte enrichment and recovery. Lymphocyte enrichment was measured using a novel approach utilizing cell sizing analysis on a Beckman Coulter Multisizer and confirmed by flow cytometry phenotypic analysis. Efficient enrichment and recovery of lymphocytes from leukapheresis cell products was achieved using modified elutriation settings for flow rate and fraction volume. Elutriation allowed for enrichment of larger numbers of lymphocytes compared with depletion of monocytes by bead adherence, with a trend toward increased lymphocyte purity and yield via elutriation, resulting in a substantial reduction in the cost of enrichment per cell. Importantly, significant lymphocyte enrichment could be accomplished using leukapheresis samples from healthy donors (n=12) or from study subjects with HIV infection (n=15) or malignancy (n=12). Clinical-scale closed-system elutriation can be performed efficiently for the selective enrichment of lymphocytes for immunotherapy protocols. This represents an improvement in cost, yield and purity over current methods that require the addition of monocyte-depleting beads.

  8. CT findings of chronic eosinophilic pneumonia

    International Nuclear Information System (INIS)

    Kigami, Yusuke; Nishizawa, Sadahiko; Kuroda, Yasumasa

    1992-01-01

    CT scans in 11 cases of chronic eosinophilic pneumonia (CEP) were reviewed. Peripheral dense opacities suggesting air-space consolidation were the most peculiar findings seen in 9 patients on CT, but 7 on chest radiographs. Five patients showed broad plate-like opacities parallel to the pleura, which were the results of resolution from the periphery of the consolidation. Diffuse interstitial opacities suggesting alveolitis were the predominant finding in 3 patients, one of which also had peripheral air-space consolidation. Follow-up CT showed no residual abnormality except one who had DIP concomitant with CEP. CT scans are useful tool for both diagnosis and follow-up of CEP. (author)

  9. Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

    Science.gov (United States)

    Sato, Hiroki; Nakajima, Nao; Takahashi, Kazuya; Hasegawa, Go; Mizuno, Ken-ichi; Hashimoto, Satoru; Ikarashi, Satoshi; Hayashi, Kazunao; Honda, Yutaka; Yokoyama, Junji; Sato, Yuichi; Terai, Shuji

    2017-01-01

    AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. RESULTS In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 ± 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs. PMID:28428721

  10. Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis.

    Science.gov (United States)

    Sato, Hiroki; Nakajima, Nao; Takahashi, Kazuya; Hasegawa, Go; Mizuno, Ken-Ichi; Hashimoto, Satoru; Ikarashi, Satoshi; Hayashi, Kazunao; Honda, Yutaka; Yokoyama, Junji; Sato, Yuichi; Terai, Shuji

    2017-04-07

    To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 ± 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs.

  11. Diffuse eosinophilic gastroenteritis with antral obstruction: a case report

    International Nuclear Information System (INIS)

    Moon, Sung Hee; Kim, Young Bok; Lee, Koung Hee

    2000-01-01

    Eosinophilic gastroenteritis is a rare disease characterized by tissue eosinophilia that can involve different layers of the gut wall and cause various gastrointestinal symptoms. We describe the UGI and CT findings of a case of diffuse eosinophilic gastroenteritis with tumor-like antral obstruction due to thickening of the submucosa and muscle layer in a 21-year-old male. (author)

  12. Diffuse eosinophilic gastroenteritis with antral obstruction: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Sung Hee; Kim, Young Bok; Lee, Koung Hee [National Police Hospital, Seoul (Korea, Republic of)

    2000-02-01

    Eosinophilic gastroenteritis is a rare disease characterized by tissue eosinophilia that can involve different layers of the gut wall and cause various gastrointestinal symptoms. We describe the UGI and CT findings of a case of diffuse eosinophilic gastroenteritis with tumor-like antral obstruction due to thickening of the submucosa and muscle layer in a 21-year-old male. (author)

  13. Mechanisms of eosinophil adhesion to endothelial cells under flow conditions

    NARCIS (Netherlands)

    Ulfman, L.H.

    2002-01-01

    Eosinophils play an important role in allergic inflammatory diseases such as allergic asthma. Infiltrates of these cells are present in the interstitium and the lumen of the bronchi of asthmatic patients. Eosinophils must pass the endothelium to enter this site of inflammation. A widely accepted

  14. Biodistribution of radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1985-01-01

    Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

  15. Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation.

    Directory of Open Access Journals (Sweden)

    Shirin Elhaik Goldman

    Full Text Available The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp mice in comparison to OVA immunized wild type (NCR1+/+ and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils' (CCL24 and Th2 CD4+ T-cells' chemoattractants (CCL17, and CCL24 in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation.

  16. 2013 Update on Celiac Disease and Eosinophilic Esophagitis

    Directory of Open Access Journals (Sweden)

    Marco Astegiano

    2013-08-01

    Full Text Available Celiac disease is a chronic, immune-mediated disorder, characterized by small intestinal inflammation and villous atrophy after the ingestion of gluten by genetically susceptible individuals. Several extraintestinal manifestations have been associated to celiac disease. Eosinophilic esophagitis is a primary disorder of the esophagus characterized by upper gastrointestinal symptoms, absence of gastroesophageal reflux disease and more than 15 eosinophils per high-power field in biopsy specimens. Both celiac disease and eosinophilic esophagitis are caused by aberrant, but distinct, immune responses to ingested antigens and can be responsive to restricted food intake. The aim of this review is to assess whether there is an association between these two pathologies. In the majority of the studies examined, including the studies in pediatric population, the prevalence of eosinophilic esophagitis in subjects with celiac disease was about 10-times that of the general population. We suggest searching for eosinophilic esophagitis in all children undergoing endoscopy for suspicious celiac disease.

  17. Eosinophilic Pleural Effusion: A Rare Manifestation of Hypereosinophilic Syndrome

    Directory of Open Access Journals (Sweden)

    Ndubuisi C. Okafor

    2009-01-01

    Full Text Available Several causes of eosinophilic pleural effusions have been described with malignancy being the commonest cause. Hypereosinophilic syndrome (HES is a rare disease and very few cases have been reported of HES presenting as eosinophilic pleural effusion (EPE. We report a case of a 26-year-old male who presented with shortness of breath. He had bilateral pleural effusions, generalized lymphadenopathy, splenomegaly, and leukocytosis with marked peripheral blood eosinophilia. The pleural fluid was exudative, with 25%–30% eosinophilis, and absence of neoplastic cells. Hypereosinophilic syndrome was diagnosed after other causes of eosinophilia were excluded. He continued to be dyspneic with persistent accumulation of eosinophilic pleural fluid, even after his peripheral eosinophil count had normalized in response to treatment. This patient represents a very unusual presentation of HES with dyspnea and pleural effusions and demonstrates that treatment based on response of peripheral eosinophil counts, as is currently recommended, may not always be clinically adequate.

  18. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

    Science.gov (United States)

    Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P

    2015-01-01

    Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

  19. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

    Directory of Open Access Journals (Sweden)

    Miguel Martillo

    2015-05-01

    Full Text Available Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

  20. Esophagitis dissecans associated with eosinophilic esophagitis in an adolescent

    Directory of Open Access Journals (Sweden)

    Marjorie-Anne R. Guerra

    2015-03-01

    Full Text Available Esophagitis dissecans superficialis and eosinophilic esophagitis are distinct esophageal pathologies with characteristic clinical and histologic findings. Esophagitis dissecans superficialis is a rare finding on endoscopy consisting of the peeling of large fragments of esophageal mucosa. Histology shows sloughing of the epithelium and parakeratosis. Eosinophilic esophagitis is an allergic disease of the esophagus characterized by eosinophilic inflammation of the epithelium and symptoms of esophageal dysfunction. Both of these esophageal processes have been associated with other diseases, but there is no known association between them. We describe a case of esophagitis dissecans superficialis and eosinophilic esophagitis in an adolescent patient. To our knowledge, this is the first case describing an association between esophageal dissecans superficialis and eosinophilic esophagitis.

  1. Mast cells and eosinophils in invasive breast carcinoma

    International Nuclear Information System (INIS)

    Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

    2007-01-01

    Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

  2. Pulmonary infiltration with eosinophils in 14 dogs

    International Nuclear Information System (INIS)

    Corcoran, B.M.; Thoday, K.L.; Henfrey, J.I.; Simpson, J.W.; Burnie, A.G.; Mooney, C.T.

    1991-01-01

    Pulmonary infiltration with eosinophils was diagnosed in 14 dogs, whose age ranged from three months to 13 years. The predominant clinical sign was coughing. Dyspnoea, tachypnoea and pruritus were also observed. An absolute circulating eosinophilia was seen in eight dogs and basophilia in five dogs. Thoracic radiographic changes were variable and were not diagnostic. Bronchoscopic evidence of mild to severe bronchitis was present in 12 dogs. Abnormal numbers of eosinophils were found in bronchoalveolar lavage samples and, or, bronchial washings in all 14 cases, but no significant bacteria were recovered. Respiratory compliance was measured in five dogs and was abnormal in three. Faecal examination for helminth parasites was carried out in four cases, a large ascarid burden being identified in one. Intradermal skin testing was carried out in three dogs but was negative in all cases. Complete remission of signs was achieved with prednisolone in 12 cases with six dogs requiring continuous or repeated treatment. Three dogs died as a direct consequence of progression of the disease

  3. Bone marrow contribution to eosinophilic inflammation

    Directory of Open Access Journals (Sweden)

    Denburg Judah A

    1997-01-01

    Full Text Available Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU, measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3Ralpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5Ralpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

  4. MONOCYTES AND MACROPHAGES IN PREGNANCY AND PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Marijke M Faas

    2014-06-01

    Full Text Available Preeclampsia is an important complication in pregnancy, characterized byhypertension and proteinuria in the second half of pregnancy. Generalizedactivation of the inflammatory response is thought to play a role in thepathogenesis of preeclampsia. Monocytes may play a central role in thisinflammatory response. Monocytes are short lived cells, that mature in thecirculation and invade into tissues upon an inflammatory stimulus anddevelop into macrophages. Macrophages are abundantly present in theendometrium and play a role in implantation and placentation in normalpregnancy. In preeclampsia, these macrophages appear to be present in largernumbers and are also activated. In the present review we focused on the roleof monocytes and macrophages in the pathophysiology of preeclampsia.

  5. Strenuous physical exercise adversely affects monocyte chemotaxis

    DEFF Research Database (Denmark)

    Czepluch, Frauke S; Barres, Romain; Caidahl, Kenneth

    2011-01-01

    Physical exercise is important for proper cardiovascular function and disease prevention, but it may influence the immune system. We evaluated the effect of strenuous exercise on monocyte chemotaxis. Monocytes were isolated from blood of 13 young, healthy, sedentary individuals participating...... in a three-week training program which consisted of repeated exercise bouts. Monocyte chemotaxis and serological biomarkers were investigated at baseline, after three weeks training and after four weeks recovery. Chemotaxis towards vascular endothelial growth factor-A (VEGF-A) and transforming growth factor...

  6. Aged mice have increased inflammatory monocyte concentration ...

    Indian Academy of Sciences (India)

    monocytes from old as compared with those from young mice. The increased classic .... several instances where the isotype control antibodies stained in a similar position but at a ..... responses in young and older adults. J. Infect. Dis. 195.

  7. Epigenetic Regulation of Monocyte and Macrophage Function

    NARCIS (Netherlands)

    Hoeksema, Marten A.; de Winther, Menno P. J.

    2016-01-01

    Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying

  8. Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immune-mediated inflammatory disease.

    Directory of Open Access Journals (Sweden)

    Rogier M Thurlings

    2009-11-01

    Full Text Available Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA, a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man.We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT. We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO. Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3 (0.95-5.1 x 10(-3 % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion.The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.

  9. Eosinophils are rare in biopsy specimens of psoriasis vulgaris.

    Science.gov (United States)

    Rosa, Gabriela; Fernandez, Anthony P; Schneider, Sarah; Billings, Steven D

    2017-12-01

    Histological features of lesional biopsies can be helpful in distinguishing psoriasis subtypes from disease mimickers. However, occasionally, classic histological features are not sufficient for distinction, and additional clues would be useful. There is a common belief that the presence of eosinophils in skin biopsies argues against psoriasis, but actual literature is scant. Skin biopsies with a diagnosis of psoriasis from 2013 to 2016 were reviewed. For inclusion, both histological and clinical features were required to be consistent with psoriasis. For biopsies meeting inclusion criteria, a detailed evaluation for typical histological parameters of psoriasis, as well as presence of dermal eosinophils, was performed. Of 85 cases meeting inclusion criteria, all had either individual or grouped intracorneal neutrophils and dilated papillary blood vessels. Diminished or complete loss of the granular cell layer was seen in 83 cases (98%), and parakeratosis was seen in 84 cases (99%). Alternatively, dermal eosinophils were seen in only 15 cases (18%). Of cases with eosinophils, none had more than 3 eosinophils upon examination of the entire dermis. Active treatment did not appear to impact presence/absence or numbers of eosinophils. Eosinophils are uncommon in psoriasis biopsies, and when present, they are found in small numbers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Nutritional management of Eosinophilic Gastroenteropathies: Case series from the community

    Directory of Open Access Journals (Sweden)

    Basilious Alfred

    2011-05-01

    Full Text Available Abstract Eosinophilic gastroenteropathies, such as eosinophilic esophagitis and eosinophilic colitis, have classically been treated with swallowed inhaled corticosteroids or oral corticosteroids. More recent studies have found elimination and elemental diets to be effective treatment alternatives to steroids. In this case series we describe the treatment of three children using nutritional management in a community setting. Elimination diets and elemental diets based on patch testing and skin prick tests reduced the eosinophil counts to normal levels in all three children. Food items which tested positive were then reintroduced while symptoms and eosinophil counts were monitored. Nutritional management of eosinophilic esophagitis and eosinophilic colitis was found to be effective in reducing symptoms. However, obstacles facing patients who choose this type of therapy include limitations due to the cost of repeated endoscopies, palatability of elimination/elemental diets and the availability of subspecialists trained in management (e.g. Allergy, Gastroenterology, and Pathology. It may be a worthwhile endeavour to overcome these obstacles as nutritional management minimizes the potential long-term effects of chronic steroid therapy.

  11. Thrombomodulin inhibits the activation of eosinophils and mast cells.

    Science.gov (United States)

    Roeen, Ziaurahman; Toda, Masaaki; D'Alessandro-Gabazza, Corina N; Onishi, Masahiro; Kobayashi, Tetsu; Yasuma, Taro; Urawa, Masahito; Taguchi, Osamu; Gabazza, Esteban C

    2015-01-01

    Eosinophils and mast cells play critical roles in the pathogenesis of bronchial asthma. Activation of both cells leads to the release of pro-inflammatory mediators in the airway of asthmatic patients. Recently, we have shown that inhaled thrombomodulin inhibits allergic bronchial asthma in a mouse model. In the present study, we hypothesize that thrombomodulin can inhibit the activation of eosinophils and mast cells. The effect of thrombomodulin on the activation and release of inflammatory mediators from eosinophils and mast cells was evaluated. Thrombomodulin inhibited the eotaxin-induced chemotaxis, upregulation of CD11b and degranulation of eosinophils. Treatment with thrombomodulin also significantly suppressed the degranulation and synthesis of inflammatory cytokines and chemokines in eosinophils and mast cells. Mice treated with a low-dose of inhaled thrombomodulin have decreased number of eosinophils and activated mast cells and Th2 cytokines in the lungs compared to untreated mice. The results of this study suggest that thrombomodulin may modulate allergic responses by inhibiting the activation of both eosinophils and mast cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Osteopontin Prevents Monocyte Recirculation and Apoptosis

    OpenAIRE

    Burdo, Tricia H.; Wood, Malcolm R.; Fox, Howard S.

    2007-01-01

    Cells of the monocyte/macrophage lineage have been shown to be the principal targets for productive HIV-1 replication within the central nervous system. In addition, HIV-1-associated dementia (HAD) has been shown to correlate with macrophage abundance in the brain. While increased entry of monocytes into the brain is thought to initiate this process, mechanisms that prevent macrophage egress from the brain and means that prevent macrophage death may also contribute to cell accumulation. We hy...

  13. Effective antigen presentation to helper T cells by human eosinophils.

    Science.gov (United States)

    Farhan, Ruhaifah K; Vickers, Mark A; Ghaemmaghami, Amir M; Hall, Andrew M; Barker, Robert N; Walsh, Garry M

    2016-12-01

    Although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. For example, murine eosinophils can present antigen to CD4 + T helper (Th) cells, but it remains unclear whether human eosinophils also have this ability. This study determined whether human eosinophils present a range of antigens, including allergens, to activate Th cells, and characterized their expression of MHC class II and co-stimulatory molecules required for effective presentation. Human peripheral blood eosinophils purified from non-allergic donors were pulsed with the antigens house dust mite extract (HDM), Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein derivative (PPD), before co-culture with autologous CD4 + Th cells. Proliferative and cytokine responses were measured, with eosinophil expression of HLA-DR/DP/DQ and the co-stimulatory molecules CD40, CD80 and CD86 determined by flow cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation, with the response strength dependent on antigen concentration. The cytokine responses varied with donor and antigen, and were not biased towards any particular Th subset, often including combinations of pro- and anti-inflammatory cytokines. Eosinophils up-regulated surface expression of HLA-DR/DP/DQ, CD80, CD86 and CD40 in culture, increases that were sustained over 5 days when incubated with antigens, including HDM, or the major allergens it contains, Der p I or Der p II. Human eosinophils can, therefore, act as effective antigen-presenting cells to stimulate varied Th cell responses against a panel of antigens including HDM, TG or PPD, an ability that may help to determine the development of allergic disease. © 2016 John Wiley & Sons Ltd.

  14. Induction of autophagy is essential for monocyte-macrophage differentiation

    OpenAIRE

    Zhang, Yan; Morgan, Michael J.; Chen, Kun; Choksi, Swati; Liu, Zheng-gang

    2012-01-01

    Monocytes are programmed to undergo apoptosis in the absence of stimulation. Stimuli that promote monocyte-macrophage differentiation not only cause cellular changes, but also prevent the default apoptosis of monocytes. In the present study, we demonstrate that autophagy is induced when monocytes are triggered to differentiate and that the induction of autophagy is pivotal for the survival and differentiation of monocytes. We also show that inhibition of autophagy results in apoptosis of cell...

  15. Ulmus davidiana var. japonica Nakai upregulates eosinophils and suppresses Th1 and Th17 cells in the small intestine.

    Directory of Open Access Journals (Sweden)

    Han-Sung Lee

    Full Text Available The bark of Ulmus davidiana var. japonica Nakai (Ulmaceae has been used in traditional Korean medicine for chronic inflammation in the gastrointestinal tract. Here we investigated the frequency and cytokine profile of the major immune cells in the small intestinal lamina propria (SI LP, spleen, and mesenteric lymph nodes (MLNs of mice treated orally with Ulmus davidiana var. japonica Nakai bark water extract (UDE to address the immunomodulatory role of this herb in intestinal homeostasis. B6 mice were given 5g/kg UDE once daily for 14 days. They were then sacrificed, and cells were isolated from the spleen, MLNs, and SI LP. The proportion of B versus T lymphocytes, CD4(+ versus CD8(+ T lymphocytes, Th1 and Th17 cells, and Foxp3(+ regulatory T cells in the spleen, MLNs, and SI LP were analyzed. The frequency of antigen-presenting cells (APCs, including dendritic cells, macrophages, and eosinophils in the SI LP and the expression of costimulatory molecules on APCs were also evaluated. The numbers and frequencies of Th1 and Th17 cells in the SI LP were significantly reduced in the UDE-treated mice compared with PBS controls. In addition, the proportion of IL-4-producing eosinophils in the SI LP was significantly elevated in the UDE-treated mice compared with controls. Taken together, these data indicate that UDE up-regulates the number and frequency of SI LP eosinophils, which can down-regulate the Th1 and Th17 responses via IL-4 secretion and contribute to intestinal homeostasis.

  16. Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Lange, Peter

    2016-01-01

    RATIONALE: Whether high blood eosinophils are associated with COPD exacerbations among individuals with COPD in the general population is largely unknown. OBJECTIVES: To test the hypothesis that high blood eosinophils predict COPD exacerbations. METHODS: Among 81,668 individuals from the Copenhagen...... General Population Study, we examined 7,225 with COPD based on spirometry. We recorded blood eosinophils at baseline and future COPD exacerbations longitudinally, defined as moderate (short-course treatment of systemic corticosteroids) or severe (hospitalization). We also assessed exacerbation risk...... in a subgroup of 203 COPD individuals with clinical COPD, defined as participants with ≥ 10 pack-years, FEV1

  17. Eosinophilic cholecystitis: an infrequent cause of acute cholecystitis

    Directory of Open Access Journals (Sweden)

    María del Moral-Martínez

    2015-01-01

    Full Text Available Eosinophilic cholecystitis (EC is a rare disease that is characterised by eosinophilic infiltration of the gallbladder. Its pathogenesis is unknown, although many hypotheses have been made. Clinical and laboratory manifestations do not differ from those of other causes of cholecystitis. Diagnosis is histological and usually performed after analysis of the surgical specimen. We report the case of a woman aged 24 years, with symptoms of fever, vomiting and pain in the right upper quadrant. When imaging tests revealed acalculous cholecystitis, an urgent cholecystectomy was performed. Histological examination of the surgical specimen revealed eosinophilic cholecystitis. No cause of the symptoms was found.

  18. Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis

    Directory of Open Access Journals (Sweden)

    Richard Hariman

    2016-01-01

    Full Text Available Eosinophilic fasciitis (EF is a rare disorder involving chronic inflammation of the fascia and connective tissue surrounding muscles, nerves, and blood vessels. While its pathogenesis is not entirely understood, this disorder is thought to be autoimmune or allergic in nature. We present here a case of a 59-year-old male who developed peripheral eosinophilia and subsequent eosinophilic fasciitis during treatment with infliximab. To our knowledge, eosinophilic fasciitis has not been previously described in patients during treatment with an inhibitor of tumor necrosis factor α.

  19. Eosinophilic cystitis in a 3-year-old boy

    International Nuclear Information System (INIS)

    Breysem, L.; Smet, M.H.; Gordts, H.; Marchal, G.

    1991-01-01

    Eosinophilic cystitis is a rare in children; it also affects adults. Clinical manifestations are variable. The diagnosis can be confirmed by cystoscopy and biopsy, both rather invasive procedures, especially in younger patients. We report a 3-year-old boy with eosinophilic cystitis. The most important radiological finding was marked thickening of the bladder wall, documented on ultrasound, cystography and CT. The CT findings of eosinophilic cystitis have, to the best of our knowledge, not been reported before. In addition to ultrasound and cystography, CT clearly demonstrates extension of the inflammatory process into the perivesical tissues. (orig.)

  20. Eosinophilic granuloma of bone in children

    International Nuclear Information System (INIS)

    Leblan, I.; Gaucher, H.; Hoeffel, J.C.; Arnould, V.; Galloy, M.A.; Mainard, L.

    1995-01-01

    Eosinophilic granuloma of bone or Langerhans cell histiocytosis is mostly unifocal. It appears on plain X Ray as a solitary destructive lesion of long bones or flat bones. Computerized tomography (CT) is useful to define the extension to the cortical bone and also to precisely localize the lesion when the anatomy is complex (hip, spine, base of the skull). Magnetic resonance (MR) is very useful in case of more aggressive lesions when there is extension to soft tissues. Differential diagnosis includes circumscribed osteitis and tumors in the case of extensive destruction. The natural course of solitary lesions is favorable, spontaneously or with therapy. The prognosis is more serious in the case of multiple lesions. (authors)

  1. Phosphatidylinositol response and proliferation of oxidative enzyme-activated human T lymphocytes: suppression by plasma lipoproteins

    International Nuclear Information System (INIS)

    Akeson, A.L.; Scupham, D.W.; Harmony, J.A.

    1984-01-01

    The phosphatidylinositol (PI) response and DNA synthesis of neuraminidase and galactose oxidase (NAGO)-stimulated human T lymphocytes are suppressed by low density lipoproteins (LDL). To understand the mechanism of lymphocyte activation more fully, the PI response and DNA synthesis and suppression of these events by LDL in NAGO-stimulated T lymphocytes were characterized. Between 30 min and 6 hr after NAGO stimulation, there was an increase of 32 Pi incorporation into PI without increased incorporation into the phosphorylated forms of PI or into other phospholipids. DNA synthesis as determined by [ 3 H]thymidine incorporation depended on the lymphocyte-accessory monocyte ratio and total cell density. Optimal stimulation of the PI response and DNA synthesis occurred at the same concentration of neuraminidase and galactose oxidase. While the PI response was only partially suppressed by LDL with optimal suppression at 10 to 20 micrograms of protein/ml, DNA synthesis was completely suppressed although at much higher LDL concentrations, greater than 100 micrograms protein/ml. As monocyte numbers are increased, LDL suppression of DNA synthesis is decreased. The ability of NAGO to stimulate the PI response and DNA synthesis in a similar way, and the suppression of both events by LDL, suggests the PI response is important for lymphocyte activation and proliferation. Stimulation of human T lymphocytes by oxidative mitogens, neuraminidase, and galactose oxidase caused increased phosphatidylinositol metabolism and increased DNA synthesis. Both responses were suppressed by low density lipoproteins

  2. Eosinophilic meningitis: a case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum.

    Science.gov (United States)

    Shah, I; Barot, S; Madvariya, M

    2015-01-01

    Eosinophilic meningitis is defined as the presence of >10 eosinophils/μL in cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte count. Eosinophilic meningitis has been reported in two case series and two case reports in India till date and has not been reported in children below 15 years of age. We present two children with eosinophilic meningitis with peripheral eosinophilia and the proposed etiologic agents based on the clinical setting and their response to antihelminthic agents.

  3. An antigen shared by human granulocytes, monocytes, marrow granulocyte precursors and leukemic blasts.

    Science.gov (United States)

    Shumak, K H; Rachkewich, R A

    1983-01-01

    An antibody to human granulocytes was raised in rabbits by immunization with granulocytes pretreated with rabbit antibody to contaminating antigens. The antibody reacted not only with granulocytes but also with monocytes and bone marrow granulocyte precursors including colony-forming units in culture (CFU-C). In tests with leukemic cells, the antibody reacted with blasts from most (8 of 9) patients with acute myelomonoblastic leukemia and from some patients with acute myeloblastic leukemia, morphologically undifferentiated acute leukemia and chronic myelogenous leukemia in blast crisis. The antibody did not react with blasts from patients with acute lymphoblastic leukemia nor with leukemic cells from patients with chronic lymphocytic leukemia.

  4. Comparison of Toxocariasis Frequency in Hyper- eosinophilic and Non-Eosinophilic Individuals Referred to Abadan Health Centers

    Directory of Open Access Journals (Sweden)

    Sharif Maraghi

    2014-07-01

    Full Text Available Background: Toxocariasis is a zoonotic helminthic infection of humans and animals caused by the larvae of intestinal parasites of dogs and cats (Toxocara canis and Toxocara cati, respectively. These nematodes develop in to their adult stage in the intestines of cats and dogs. Three clinical entities have been recognized in humans; visceral larva migrans, ocular larva migrans and covert toxocariasis. Eosinophilia is a common finding in infected patients Objectives: In this study the frequency of toxocariasis in eosinophilic and non-eosinophilic individuals referred to the laboratory of Abadan health centers was compared. Materials and Methods: Serum samples were collected from individuals attending the laboratory of health centers for any medical problem and were tested for complet blood count (CBC. The samples of patients were divided in to two groups, those with more than 10% peripheral eosinophils, as the eosinophilic group (n = 54 and those with normal eosinophils (0-3% as the non-eosinophilic group (n = 54. Samples were examined for anti-oxocara IgG by the enzyme linked immunosorbent assay (ELISA and confirmed western blotting. Results: Anti-oxocara IgG was detected in the sera of six (11.11% cases from the eosinophilic group and two (3.7% of the non-eosinophilic group by the ELISA method, but all had negative results for the western blot analysis. Conclusions: The results of this study indicated that the eosinophilic individuals might beexposed to other helminthic infections or allergic agents. Further studies are required with more samples with different ages and occupations.

  5. C:\\BACKUP 21.01.2015\\All 5d1a\\BAJOPAS\\Bajopas 8(1)

    African Journals Online (AJOL)

    User

    2015-01-21

    Jan 21, 2015 ... Females had higher prevalence rate(18%) of Malaria infection than males with 7.5%. ... is endemic in region of the world including sub- ..... neutrophil, LYM: lymphocyte, MON: monocyte, EOS: eosinophil , BAS: basophils.

  6. Lactation performance and serum biochemistry of dairy cows fed ...

    African Journals Online (AJOL)

    Serum biochemistry concentrations (serum glucose, cholesterol, triglyceride, total protein, and cortisol and insulin concentration) and blood hematology (red blood cell, hematocrit, hemoglobin concentration and percentage neutrophils, lymphocytes, monocytes, basophiles, eosinophils and ratio of neutrophils to ...

  7. Transcellular lipoxygenase metabolism between monocytes and platelets

    Energy Technology Data Exchange (ETDEWEB)

    Bigby, T.D.; Meslier, N. (Univ. of California, San Francisco (USA))

    1989-09-15

    We have examined the effects of co-culture and in vitro co-stimulation on lipoxygenase metabolism in monocytes and platelets. Monocytes were obtained from the peripheral blood of normal volunteers by discontinuous gradient centrifugation and adherence to tissue culture plastic. Platelets were obtained from the platelet-rich plasma of the same donor. When 10(9) platelets and 2.5 x 10(6) monocytes were co-stimulated with 1 microM A23187, these preparations released greater quantities of 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid, 5(S),12-(S)dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, and leukotriene C4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic (LTC4) when compared with monocytes alone. Release of arachidonic acid, 5-HETE, delta 6-trans-LTB4, and delta 6-trans-12-epi-LTB4 from monocytes was decreased in the presence of platelets. A dose-response curve was constructed and revealed that the above changes became evident when the platelet number exceeded 10(7). Dual radiolabeling experiments with 3H- and 14C-arachidonic acid revealed that monocytes provided arachidonic acid, 5-HETE, and LTA4 for further metabolism by the platelet. Monocytes did not metabolize platelet intermediates detectably. In addition, as much as 1.2 microM 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid and 12(S)-hydroperoxy-10-trans-5,8,14-cis-eicosatetraenoic acid had no effect on monocyte lipoxygenase metabolism. Platelets were capable of converting LTA4 to LTC4, but conversion of LTA4 to LTB4 was not detected. We conclude that the monocyte and platelet lipoxygenase pathways undergo a transcellular lipoxygenase interaction that differs from the interaction of the neutrophil and platelet lipoxygenase pathways. In this interaction monocytes provide intermediate substrates for further metabolic conversion by platelets in an unidirectional manner.

  8. Characterization and antagonism of cytokine-induced eosinophil priming

    NARCIS (Netherlands)

    Rosas Rosas, Ana Marcela

    2006-01-01

    Allergic asthma is an inflammatory disease characterized by bronchial hyper-responsiveness, airway inflammation, and reversible obstruction of the airways. In humans, cytokine activated eosinophils are thought to be important players in this process since they can release inflammatory mediators

  9. Eosinophilic granuloma in the anterior mandible mimicking radicular cyst

    International Nuclear Information System (INIS)

    Lee, Byung Do; Lee, Wan; Lee, Jun; Son, Hyun Jin

    2013-01-01

    Eosinophilic granuloma is a common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. The radiographic appearance of eosinophilic granuloma in the jaw is variable and not specific. It may resemble periodontitis, radicular cyst, or malignancies. The purpose of this report is to describe the characteristic radiographic features of eosinophilic granuloma of a 39-year-old male. The lesion in the anterior mandible was first diagnosed as radicular cyst because the radiographic findings were ovoid radiolucent lesion with well-defined border. However, careful interpretation revealed a non-corticated border and floating tooth appearance that were the characteristic radiographic features for the differential diagnosis. Early clinical signs of eosinophilic granuloma can occur in the jaw and a bony destructive lesion might be mistaken for periodontitis or an odontogenic cystic lesion; therefore, careful interpretation of radiographs should be emphasized.

  10. Eosinophilic granuloma in the anterior mandible mimicking radicular cyst

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Do; Lee, Wan; Lee, Jun [College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Son, Hyun Jin [Dept. of Pathology, School of Medicine, Eulji University, Daejeon (Korea, Republic of)

    2013-06-15

    Eosinophilic granuloma is a common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. The radiographic appearance of eosinophilic granuloma in the jaw is variable and not specific. It may resemble periodontitis, radicular cyst, or malignancies. The purpose of this report is to describe the characteristic radiographic features of eosinophilic granuloma of a 39-year-old male. The lesion in the anterior mandible was first diagnosed as radicular cyst because the radiographic findings were ovoid radiolucent lesion with well-defined border. However, careful interpretation revealed a non-corticated border and floating tooth appearance that were the characteristic radiographic features for the differential diagnosis. Early clinical signs of eosinophilic granuloma can occur in the jaw and a bony destructive lesion might be mistaken for periodontitis or an odontogenic cystic lesion; therefore, careful interpretation of radiographs should be emphasized.

  11. Eosinophilic Granulomatosis with Polyangiitis, formerly Churg-Strauss Syndrome (EGPA)

    Science.gov (United States)

    ... Strauss Syndrome (EGPA) Eosinophilic Granulomatosis with Polyangiitis, formerly Churg-Strauss Syndrome (EGPA) First Description Who gets EGPA (the “ ... granulomatosis with polyangiitis (EGP), formerly known as the Churg-Strauss Syndrome , is a systemic vasculitis. This disease was ...

  12. Esophageal dilations in eosinophilic esophagitis: A single center experience

    OpenAIRE

    Ukleja, Andrew; Shiroky, Jennifer; Agarwal, Amitesh; Allende, Daniela

    2014-01-01

    AIM: To diagnose the clinical and histologic features that may be associated with or predictive of the need for dilation and dilation related complications; examine the safety of dilation in patients with eosinophilic esophagitis (EoE).

  13. Psychological distress in patients with morphea and eosinophilic fasciitis.

    NARCIS (Netherlands)

    Kroft, Ilse; Jong, E.M.G.J. de; Evers, A.W.M.

    2009-01-01

    OBJECTIVE: To examine the level of psychological distress and factors contributing to distress in patients with morphea or eosinophilic fasciitis. DESIGN: Cross-sectional study. SETTING: Dermatology outpatient clinic of a university hospital. PARTICIPANTS: Of 120 patients with morphea or

  14. Emerging Roles for Eosinophils in the Tumor Microenvironment.

    Science.gov (United States)

    Reichman, Hadar; Karo-Atar, Danielle; Munitz, Ariel

    2016-11-01

    Eosinophils are evolutionary conserved cells largely studied in the context of allergy. Although eosinophils were first described in tumors more than 120 years ago, their roles in cancer are often overlooked. This is puzzling given their potent immune modulatory, cytotoxic, and/or tissue repair capabilities, and recent studies demonstrating key roles for eosinophils in contexts far beyond their 'classical' field (e.g., metabolism, thermogenesis, and tissue regeneration). Recent data suggest that this frequently ignored cell is emerging as a potent immune effector and immune modulator in the tumor microenvironment. This review discusses the relevance of eosinophils to tumorigenesis and the potential to harness their function in cancer therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Mathiesen, Lars Reinhardt

    1991-01-01

    Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited...

  16. Eosinophilic Gastroenteritis as a Rare Cause of Recurrent Epigastric Pain

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Safari

    2016-04-01

    Full Text Available Eosinophilic gastroenteritis (EGE is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. It can mimic many gastrointestinal disorders due to its wide spectrum of presentations. Diagnose is mostly based on excluding other disorders and a high suspicion. Here we report a case of 26 year old man with a history of sever epigastric pain followed by nausea, vomiting since a few days before admission with final diagnosis of EGE.

  17. Eosinophilic ascites: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Raed M Alsulaiman

    2015-01-01

    Full Text Available Eosinophilic gastroenteritis is a rare gastrointestinal (GI disorder characterized by nonspecific GI symptoms, peripheral eosinophilia, and eosinophilic infiltration of the intestinal wall. The disorder is classified into mucosal, muscular, and sub-serosal types, depending on the clinical picture and the depth of eosinophilic infiltration within the GI wall. Sub-serosal disease, which is complicated by ascites, usually results in the most severe clinical form of eosinophilic gastroenteritis and requires early corticosteroid therapy. In such cases, a favorable outcome can be achieved after a short course of corticosteroids. We present the case of a 28-year-old female with diffuse abdominal pain and distention for 2 weeks. Her physical examination was significant for moderate ascites. Initial work-up demonstrated severe peripheral blood eosinophilia, normal liver function tests, and elevated serum immunoglobulin E (IgE. Upper endoscopy, colonoscopy showed a thickening of the stomach and colon, and biopsies showed marked eosinophilic infiltration of the mucosa. Ascitic fluid analysis showed significant eosinophilia. Subsequent treatment with oral prednisone resulted in the normalization of laboratory and radiologic abnormalities 45 days after the start of the treatment. Despite its rarity, eosinophilic gastroenteritis needs to be recognized by the clinician because the disease is treatable, and timely diagnosis and initiation of treatment could be of major importance.

  18. Cytological diagnostic of lymphadenitis tuberculosis by eosinophilic material

    Science.gov (United States)

    Delyuzar; Amir, Z.; Kusumawati, L.

    2018-03-01

    AFB sputum and chest X-ray are used to identify patients with pulmonary TB. For extrapulmonary TB, fine needle aspiration cytology is needed, even though occasionally found not atypical feature in the form of eosinophilic material with dark brown particles, suspected as TB. This research was to show that eosinophilic material with dark brown particles is accurate as new criteria for the cytological diagnosis of TB. By performing fine needle aspiration biopsy stained with Giemsa, if an eosinophilic material with dark brown particles was encountered, we continued with Ziehl-Neelsen AFB stain and confirmed with PCR. To assess accuracy, we used a diagnostic test to evaluate sensitivity and specificity of eosinophilic material with dark brown particles by using AFB and PCR as the gold standard. The sensitivity and specificity of cytological diagnosis in tuberculosis of eosinophilic material with dark brown particles were 93.65% and 70.99%, respectively if confirmed with AFB. On the other hand, if confirmed with PCR using Mycobacterium tuberculosis DNA, the sensitivity and specificity were 98.95% and 96.79%, respectively. In conclusion, eosinophilic masses with dark brown particles is accurate as new criteria of TB diagnostic cytology with high sensitivity and specificity confirmed with AFB and PCR test.

  19. Higher frequency of cholelithiasis in eosinophilic cholecystitis, an unusual finding

    International Nuclear Information System (INIS)

    Sarfraz, T.; Tariq, H.; Bashir, S.

    2015-01-01

    To determine the frequency of cholelithiasis in eosinophilic cholecystitis in our population. Study Design: Prospective descriptive study. Place and Duration of Study: Histopathology department, Combined Military Hospital (CMH), Peshawar (Pakistan) from Dec 2011 to Nov 2014. Material and Methods: Eighteen hundred (1800) cholecystectomy specimens were included in the study. The specimens which were properly fixed in 10% formalin were included in the specimen, while poorly fixed and autolysed specimens were excluded. The specimens were examined grossly, measured and block selection was done. The slides made were examined under light microscope by one histopathologist and findings were analyzed. Results: Out of 1800 cholecystectomy specimens, 25 cases (1.38%) were diagnosed as eosinophilic cholecystitis. Out of these 25 cases, 20 (80%) were females having an age range of 30-50 years, while 5 (20%) were males with an age range of 35-55 years. Out of these 25 cases of eosinophilic cholecystitis, 22 (88%) were having cholelithiasis, while 3 (12%) were acalculous eosiniophilic cholecystitis. Conclusion: Eosinophilic cholecystitis in our population is mostly calculous which is very significant finding contrary to data given in western literature, where most of eosinophilic cholecystitis is aclculous. This needs further evaluation to determine any genetic, geographic, environmental, dietary, microbiological or any other factor responsible in etiopathogenesis of calculous eosinophilic cholecystitis in our population, which could be helpful in prevention and management of this disease. (author)

  20. Eosinophils from Physiology to Disease: A Comprehensive Review

    Science.gov (United States)

    Yacoub, Mona-Rita; Ripa, Marco; Mannina, Daniele; Cariddi, Adriana; Saporiti, Nicoletta; Ciceri, Fabio; Castagna, Antonella; Dagna, Lorenzo

    2018-01-01

    Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances. PMID:29619379

  1. Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN). Detection by enzyme-linked immunosorbent assay and purification from normal human urine

    DEFF Research Database (Denmark)

    Reimert, C M; Minuva, U; Kharazmi, A

    1991-01-01

    Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) is one of the cationic proteins found in the granules of the human eosinophilic granulocytes. EPX was purified from extracts of granules isolated from blood buffy coat cells of healthy donors. Polyclonal anti-EPX antibodies were...

  2. Eosinophils increase in animals that received biotherapic

    Directory of Open Access Journals (Sweden)

    Pedro Gilberto Silva Morais

    2012-12-01

    morphological changes in juveniles and adults ticks parasitizing animals which consumed the biotherapic. This observation suggests a negative interference of the biotherapic in the biological cycle of the tick, decreasing its population and consequently his control’s necessity. Comparing the blood cells counts of the first and the twelfth month, a raise of 23% (P> 0.05 in the eosinophils and 8% (P< 0.05 in the platelets was observed in the T1 animals. No changes in liver enzymes were observed. The increase in eosinophils and platelets found in this experiment suggests that biotherapic ingested by the animals strengthens the defense system and the clotting cascade.Key words: bovinos

  3. Human vs. Mouse Eosinophils: “That which we call an eosinophil, by any other name would stain as red”

    Science.gov (United States)

    Lee, James J.; Jacobsen, Elizabeth A.; Ochkur, Sergei I; McGarry, Michael P.; Condjella, Rachel M.; Doyle, Alfred D.; Luo, Huijun; Zellner, Katie R.; Protheroe, Cheryl A.; Willetts, Lian; LeSuer, William E.; Colbert, Dana C.; Helmers, Richard A.; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A.

    2012-01-01

    The respective life histories of humans and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiological pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils and/or their effector functions. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide the experimental details, comparing and contrasting eosinophils and eosinophil effector functions in humans vs. mice. In particular, our review will provide a summation and an easy to use reference guide to important studies demonstrating that while differences exist, more often than not their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function, but instead, species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. PMID:22935586

  4. Human versus mouse eosinophils: "that which we call an eosinophil, by any other name would stain as red".

    Science.gov (United States)

    Lee, James J; Jacobsen, Elizabeth A; Ochkur, Sergei I; McGarry, Michael P; Condjella, Rachel M; Doyle, Alfred D; Luo, Huijun; Zellner, Katie R; Protheroe, Cheryl A; Willetts, Lian; Lesuer, William E; Colbert, Dana C; Helmers, Richard A; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A

    2012-09-01

    The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  5. Osseous eosinophilic granuloma in children; Le granulome eosinophile des os chez l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Leblan, I.; Gaucher, H.; Marinard, L.; Galloy, M.A.; Phi, I.N.; Hoeffel, J.C. [Hopital de Brabois-Vandoeuvre, 54 - Nancy (France). Service de radiologie

    2001-02-01

    Eosinophilic granuloma of bone or Langerhans cell histiocytosis is mostly uni-focal. It appears on plain X Ray as a solitary destructive lesion of long bones or flat bones. CT is useful to define the extension to the cortical bone and also to precisely localize the lesion when the anatomy is complex (hip, spine, base of the skull). MR is very useful in case of more aggressive lesions when there is extension to soft tissues. Differential diagnosis includes circumscribed osteitis and tumors prognosis is more serious in case of multiple lesions. (authors)

  6. In vitro interactions of lymphocytes and cultured cells from beagles with plutonium-induced bone tumors

    International Nuclear Information System (INIS)

    Frazier, M.E.; Lund, J.E.; Busch, R.H.

    1976-01-01

    Cell cultures have been prepared from lung and bone tumors arising in beagle dogs following exposure to inhaled plutonium. Evaluation of the cultured cells by commonly applied criteria (i.e., cell morphology, lack of contact inhibitory mechanisms, cloning efficiency, growth in soft agar, and tumor production in vivo) indicated that tumor cells were being grown in culture. Blood leukocytes and peripheral lymphocytes from beagle dogs were tested for cytotoxic effects against several cell cultures. Lymphocytes from normal dogs or dogs with unrelated tumors would not kill the bone tumor cells unless monocytes (macrophage) were present, in which case the leukocyte preparation was capable of mounting de novo cytotoxic immune reactions after 3 to 5 days in culture. In contrast, the dogs with plutonium-induced bone tumors had circulating lymphocytes that appeared to have undergone presensitization to bone-tumor-distinctive antigens in vivo. Consequently these lymphocytes interacted with cultured cells promptly after encounter in vitro

  7. Protein Translation and Signaling in Human Eosinophils

    Directory of Open Access Journals (Sweden)

    Stephane Esnault

    2017-09-01

    Full Text Available We have recently reported that, unlike IL-5 and GM-CSF, IL-3 induces increased translation of a subset of mRNAs. In addition, we have demonstrated that Pin1 controls the activity of mRNA binding proteins, leading to enhanced mRNA stability, GM-CSF protein production and prolonged eosinophil (EOS survival. In this review, discussion will include an overview of cap-dependent protein translation and its regulation by intracellular signaling pathways. We will address the more general process of mRNA post-transcriptional regulation, especially regarding mRNA binding proteins, which are critical effectors of protein translation. Furthermore, we will focus on (1 the roles of IL-3-driven sustained signaling on enhanced protein translation in EOS, (2 the mechanisms regulating mRNA binding proteins activity in EOS, and (3 the potential targeting of IL-3 signaling and the signaling leading to mRNA binding activity changes to identify therapeutic targets to treat EOS-associated diseases.

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

    Science.gov (United States)

    Dogru, M; Citli, R

    2017-01-01

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

  9. Human T Lymphocytes Are Permissive for Dengue Virus Replication.

    Science.gov (United States)

    Silveira, Guilherme F; Wowk, Pryscilla F; Cataneo, Allan H D; Dos Santos, Paula F; Delgobo, Murilo; Stimamiglio, Marco A; Lo Sarzi, Maria; Thomazelli, Ana Paula F S; Conchon-Costa, Ivete; Pavanelli, Wander R; Antonelli, Lis R V; Báfica, André; Mansur, Daniel S; Dos Santos, Claudia N Duarte; Bordignon, Juliano

    2018-05-15

    Dengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course. In the present study, we have demonstrated that primary human naive CD4 + and CD8 + T cells are permissive for DV infection. Importantly, both T cell subtypes support viral replication and secrete viable virus particles. DV infection triggers the activation of both CD4 + and CD8 + T lymphocytes, but preactivation of T cells reduces the susceptibility of T cells to DV infection. Interestingly, the cytotoxicity-inducing protein granzyme A is highly secreted by human CD4 + but not CD8 + T cells after exposure to DV in vitro Additionally, using annexin V and polycaspase assays, we have demonstrated that T lymphocytes, in contrast to monocytes, are resistant to DV-induced apoptosis. Strikingly, both CD4 + and CD8 + T cells were found to be infected with DV in acutely infected dengue patients. Together, these results show that T cells are permissive for DV infection in vitro and in vivo , suggesting that this cell population may be a viral reservoir during the acute phase of the disease. IMPORTANCE Infection by dengue virus (DV) causes a flu-like disease that can evolve to severe hemorrhaging and death. T lymphocytes are important cells that regulate antibody secretion by B cells and trigger the death of infected cells. However, little is known about the direct interaction between DV and T lymphocytes. Here, we show that T lymphocytes from healthy donors are susceptible to infection by DV, leading to cell activation. Additionally, T cells seem to be resistant to DV-induced apoptosis, suggesting a potential role as a viral reservoir in humans. Finally, we show

  10. STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

    DEFF Research Database (Denmark)

    Fredholm, Simon; Gjerdrum, Lise Mette R; Willerslev-Olsen, Andreas

    2014-01-01

    Eosinophil granulocytes have been implicated in anticancer immunity but recent data indicate that eosinophils can also promote cancer. Herein, we studied eosinophils in skin lesions from 43 patients with mycosis fungoides (MF). The presence of eosinophils correlated with disease stage: 78......% of patients with advanced disease displayed eosinophil infiltration, whereas this was only seen in 11% of patients with patches (p...) in malignant T-cells also stained positively for eosinophils, whereas this was only observed in 28% of pY-STAT3-negative patients (peosinophilic activation and trafficking factors: High-mobility group BOX-1 protein (HMGB1) and interleukin 5 (IL5). STAT3 si...

  11. Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

    Science.gov (United States)

    Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

    2015-08-01

    Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Regulation of ICAM-1 in Cells of the Monocyte/Macrophage System in Microgravity

    Directory of Open Access Journals (Sweden)

    Katrin Paulsen

    2015-01-01

    Full Text Available Cells of the immune system are highly sensitive to altered gravity, and the monocyte as well as the macrophage function is proven to be impaired under microgravity conditions. In our study, we investigated the surface expression of ICAM-1 protein and expression of ICAM-1 mRNA in cells of the monocyte/macrophage system in microgravity during clinostat, parabolic flight, sounding rocket, and orbital experiments. In murine BV-2 microglial cells, we detected a downregulation of ICAM-1 expression in clinorotation experiments and a rapid and reversible downregulation in the microgravity phase of parabolic flight experiments. In contrast, ICAM-1 expression increased in macrophage-like differentiated human U937 cells during the microgravity phase of parabolic flights and in long-term microgravity provided by a 2D clinostat or during the orbital SIMBOX/Shenzhou-8 mission. In nondifferentiated U937 cells, no effect of microgravity on ICAM-1 expression could be observed during parabolic flight experiments. We conclude that disturbed immune function in microgravity could be a consequence of ICAM-1 modulation in the monocyte/macrophage system, which in turn could have a strong impact on the interaction with T lymphocytes and cell migration. Thus, ICAM-1 can be considered as a rapid-reacting and sustained gravity-regulated molecule in mammalian cells.

  13. Labeling of autologous monocytes with 99mTc-HMPAO at very high specific radioactivity

    International Nuclear Information System (INIS)

    Hemert, Formijn J. van; Thurlings, Rogier; Dohmen, Serge E.; Voermans, Carlijn; Tak, Paul P.; Eck-Smit, Berthe L.F. van; Bennink, Roelof J.

    2007-01-01

    Rheumatoid arthritis of joints involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration can be portrayed scintigraphically in order to monitor noninvasive effects of therapy on the progress of the disease. Scintigraphic detection of inflammation by means of technetium 99m-hexamethylpropylene amine oxime ( 99m Tc-HMPAO)-labeled leukocytes provides a classic example. Present state-of-the-art methods in cell biology allow the isolation of cells like lymphocytes or monocytes, which are less abundant than main blood constituents but, instead, harbor particular functions like specific homing properties. To facilitate scintigraphic imaging of the cell functions involved, the relatively small population of cells must be labeled to radioactive yields as high as possible. We demonstrate that autologous monocytes isolated from 100 ml of peripheral blood can be radiolabeled to a yield of 10 (instead of 1) Bq per cell, allowing scintigraphic analysis of rheumatoid arthritis up to 20 h post injection of patients. The method is based on the instantaneous distribution of lipophilic 99m Tc-HMPAO between the hydrophobic inside of cells and the hydrophilic (aqueous) surrounding of cells, followed by decomposition of the radiopharmaceutical into compounds that are unable to cross the cellular membrane. The procedure provides a method of choice for cell-mediated scintigraphy at low availability of cells with the correct homing properties

  14. Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

    International Nuclear Information System (INIS)

    Huang, Jia-Jia; Li, Zhi-Ming; Li, Ya-Jun; Xia, Yi; Wang, Yu; Wei, Wen-Xiao; Zhu, Ying-Jie; Lin, Tong-Yu; Huang, Hui-Qiang; Jiang, Wen-Qi

    2013-01-01

    Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL

  15. Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma.

    Science.gov (United States)

    Huang, Jia-Jia; Li, Ya-Jun; Xia, Yi; Wang, Yu; Wei, Wen-Xiao; Zhu, Ying-Jie; Lin, Tong-Yu; Huang, Hui-Qiang; Jiang, Wen-Qi; Li, Zhi-Ming

    2013-05-03

    Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL.

  16. Maturation and demise of human primary monocytes by carbon nanotubes

    KAUST Repository

    De Nicola, Milena D.; Mirabile Gattia, Daniele; Traversa, Enrico; Ghibelli, Lina

    2013-01-01

    -competent monocytes by mechanisms related to the presence of large nanoparticle aggregates, suggesting phenomena of bulk toxicity possibly consisting of frustrated phagocytosis. At the same time, MWCNT stimulate adhesion of the phagocytosis-incompetent monocytes

  17. Isolating peripheral lymphocytes by density gradient centrifugation and magnetic cell sorting.

    Science.gov (United States)

    Brosseron, Frederic; Marcus, Katrin; May, Caroline

    2015-01-01

    Combining density gradient centrifugation with magnetic cell sorting provides a powerful tool to isolate blood cells with high reproducibility, yield, and purity. It also allows for subsequent separation of multiple cell types, resulting in the possibility to analyze different purified fractions from one donor's sample. The centrifugation step divides whole blood into peripheral blood mononuclear cells (PBMC), erythrocytes, and platelet-rich plasma. In the following, lymphocyte subtypes can be consecutively isolated from the PBMC fraction. This chapter describes enrichment of erythrocytes, CD14-positive monocytes and CD3-positive T lymphocytes. Alternatively, other cell types can be targeted by using magnetic beads specific for the desired subpopulation.

  18. Lymphocytic Colitis: Pathologic predictors of response to therapy.

    Science.gov (United States)

    Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

    2018-02-13

    While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

  19. Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.

    Science.gov (United States)

    Andersson, Jennie; Cromvik, Julia; Ingelsten, Madeleine; Lingblom, Christine; Andersson, Kerstin; Johansson, Jan-Erik; Wennerås, Christine

    2014-12-01

    Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Eosinophils in Homeostasis and Their Contrasting Roles during Inflammation and Helminth Infections.

    Science.gov (United States)

    Strandmark, Julia; Rausch, Sebastian; Hartmann, Susanne

    2016-01-01

    Eosinophil numbers are highly elevated during helminth infections and a range of allergic and inflammatory disorders, but eosinophils are also present in several tissues in the absence of infection. Indeed, new findings demonstrate that eosinophils may be involved in events as diverse as glucose metabolism, mammary gland development, intestinal health, tissue remodeling, thymic selection, and B-cell survival. Although eosinophils often correlate with pathological parameters during conditions such as inflammatory bowel disease and asthma, the evidence for their contribution to tissue pathology remains controversial. Recent research suggests that eosinophils may have additional roles in these settings that are related to control and resolution of inflammation. Controversy also surrounds the involvement of eosinophils in anti-helminth immunity. Their assumed role in fighting parasites has increasingly been questioned, particularly as a result of data from studies of eosinophil-ablated mouse strains in which either no or only very moderate effects on helminth survival has been reported. Helminths are masters of immune regulation, but whether they actively suppress eosinophil function has rarely been considered. Thus, the purpose of this review is threefold: (1) to summarize our knowledge of the wide range of functions of eosinophils during homeostasis, (2) to discuss the role of eosinophil during inflammation and the recent discovery of eosinophils as mediators of inflammatory resolution, and (3) to summarize data on the effect of eosinophils on helminth infections and discuss the possibility of helminth-mediated modulation of eosinophils.

  1. Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

    Science.gov (United States)

    Muniz, Valdirene S; Baptista-Dos-Reis, Renata; Benjamim, Claudia F; Mata-Santos, Hilton A; Pyrrho, Alexandre S; Strauch, Marcelo A; Melo, Paulo A; Vicentino, Amanda R R; Silva-Paiva, Juliana; Bandeira-Melo, Christianne; Weller, Peter F; Figueiredo, Rodrigo T; Neves, Josiane S

    2015-01-01

    Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.

  2. Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

    Science.gov (United States)

    Mulder, Daniel J; Pooni, Aman; Mak, Nanette; Hurlbut, David J; Basta, Sameh; Justinich, Christopher J

    2011-02-01

    Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Production of C-reactive protein by human lymphocytes

    International Nuclear Information System (INIS)

    Kuta, A.E.; Baum, L.L.

    1986-01-01

    C-reactive protein (CRP) is a major acute phase serum protein in humans; it is detectable at very high concentrations during infection and tissue trauma. This protein is a pentame composed of five identical, 21,500 MW subunits. CRP is detectable on the surface of approximately 4% of normal peripheral blood lymphocytes (PBL). CRP binds its physiological ligands in a Ca ++ dependent manner; removal of Ca ++ does not alter the expression of CRP on the lymphocyte surface. Recently, investigators in this laboratory reported substantial inhibition of natural killer cell (NK) activity with anti-CRP antibodies. The following studies were undertaken to determine the origin of surface-CRP (S-CRP) found on normal PBL. Cells were incubated in methionine-free DMEM supplemented with 35 S-methionine. Cells were lysed and subjected to immunoprecipitation with anti-CRP and Staphylococcus aureus; immunoprecipitates were analyzed by SDS-PAGE and autoradiography. Data presented here suggested that lymphocytes, in particular, LGL produce small amounts of CRP and express it on their surface. Lymphocytes do not appear to secrete CRP since no CRP could be detected in culture supernatants. In addition, preliminary evidence indicates that peripheral blood monocytes produce no detectable CRP. Present studies utilizing Northern blot analysis are underway in order to detect CRP-mRNA

  4. Eosinophilic esophagitis: manometric and pHmetric findings

    Directory of Open Access Journals (Sweden)

    Monica Maria Cardoso Monnerat

    2012-06-01

    Full Text Available CONTEXT: Eosinophilic esophagitis is an entity characterized by an esophageal inflammatory infiltrate of eosinophils, manifested by dysphagia, intermittent food impactions and symptoms similar to gastroesophageal reflux disease (GERD, that predominantly affects young adults. There may be association of eosinophilic esophagitis with GERD, and motor abnormalities have been described. OBJECTIVE: The main objectives of this study are to describe the findings at esophageal manometry and pH monitoring in patients with eosinophilic esophagitis. METHODS: Cross-sectional study of 20 patients with a diagnosis of eosinophilic esophagitis, submitted to esophageal manometry and 24h pH monitoring. Were analysed the manometric changes and the presence of abnormal reflux on pH monitoring. RESULTS: Twenty patients (15 men, 5 women had a mean age of 29 years. Motility disorders were found in 25% (5/20 patients with ineffective esophageal motility being the most common finding. pH monitoring revealed abnormal reflux on 25%, without any relationship with manometric findings. CONCLUSIONS: Manometric abnormalities were observed in 25% of patients and abnormal reflux on pH monitoring also in 25%. This study showed no relationship between abnormal reflux and the presence of manometric changes.

  5. Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause

    Directory of Open Access Journals (Sweden)

    Shunichi Shibazaki

    2016-01-01

    Full Text Available Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case  1, whereas a corticosteroid and albendazole were used in Case  2 as induction therapy. Both patients recovered. Albendazole was also used in Case  1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole.

  6. Eosinophilic Colitis: University of Minnesota Experience and Literature Review

    Directory of Open Access Journals (Sweden)

    Wolfgang B. Gaertner

    2011-01-01

    Full Text Available Eosinophilic colitis is a rare form of primary eosinophilic gastrointestinal disease that is poorly understood. Neonates and young adults are more frequently affected. Clinical presentation is highly variable depending on the depth of inflammatory response (mucosal, transmural, or serosal. The pathophysiology of eosinophilic colitis is unclear but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Diagnosis is that of exclusion and differential diagnoses are many because colonic tissue eosinophilia may occur with other colitides (parasitic, drug-induced, inflammatory bowel disease, and various connective tissue disorders. Similar to other eosinophilic gastrointestinal disorders, steroid-based therapy and diet modification achieve very good and durable responses. In this paper, we present our experience with this rare pathology. Five patients (3 pediatric and 2 adults presented with diarrhea and hematochezia. Mean age at presentation was 26 years. Mean duration of symptoms before pathologic diagnosis was 8 months. Mean eosinophil count per patient was 31 per high-power field. The pediatric patients responded very well to dietary modifications, with no recurrences. The adult patients were treated with steroids and did not respond. Overall mean followup was 22 (range, 2–48 months.

  7. Feline familial pedal eosinophilic dermatosis in two littermates

    Directory of Open Access Journals (Sweden)

    Charline Pressanti

    2015-04-01

    Full Text Available In cats, the most common eosinophilic dermatoses are feline miliary dermatitis and eosinophilic granuloma complex. The most commonly identified underlying cause is a hypersensitivity reaction. Few cases of familial forms of eosinophilic dermatoses are reported in the literature. Two young adult cats from the same litter presented 2 years apart with a severe and chronic fluid or tissue infiltration of the distal part of several limbs. Lesions started on the forelegs and developed on the other limbs. Cytological and histopathological examinations showed lesions consistent with an atypical form of feline eosinophilic dermatosis associated with secondary bacterial infection. In both cats, antibiotics combined with immunosuppressive treatment partially improved the lesions, which continued to progress on a waxing and waning course, even in the absence of treatment. Allergy work-up did not permit the identification of an underlying allergic triggering factor. The severity of the lesions, the unusual presentation and the unsatisfactory response to immunosuppressive therapy in two feline littermates suggested a genetic form of eosinophilic dermatosis.

  8. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

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

  9. Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia

    OpenAIRE

    Cubillos-Zapata, Carolina; Avendaño-Ortiz, Jose; Córdoba, Raúl; Hernández-Jiménez, Enrique; Toledano, Victor; Pérez de Diego, Rebeca; López-Collazo, Eduardo

    2016-01-01

    Ibrutinib has emerged as a promising therapy for patients with chronic lymphocytic leukemia (CLL) who are nonresponsive to standard therapies. The refractory state of monocytes and T-cell exhaustion in patients with CLL could explain the morbidity and mortality reported in these patients. We studied the effect of ibrutinib on the immune response of four relapsed patients with CLL during the first treatment cycle. We observed the ability to recover the standard response against bacterial stimu...

  10. In vivo imaging of monocyte trafficking with 18F-fluorodeoxyglucose labeled monocytes

    International Nuclear Information System (INIS)

    Paik, Jin Young; Lee, Kyung Han; Han, Yu Mi; Choe, Yearn Seong; Kim, Byung Tae

    2000-01-01

    Since the ability to monitor in vivo monocyte trafficking would contribute to our understanding of the pathophysiology of various inflammatory disorders, we investigated the feasibility of labeling human monocytes with 18 F-FDG. Human monocytes were separated by Ficoll/Hypaque gradient and purity was assessed by flow cytometry. The influence of insulin and/or glucose on labeling efficiency was evaluated. Cell viability and activation was measured with trypan blue exclusion and hydrogen peroxide assays, respectively. Label stability was measured for up to 18 hr, and the effect of insulin pre-incubation on FDG washout was investigated. PET images were acquired in SD rats at various time points after injection of FDG labeled monocytes. Monocytes were >85% pure, and labeling efficiency was 35% for 1x106 cells after 40 min incubation with 2 mCi 18 F-FDG without insulin. Pre-incubation with 10∼100 nM insulin significantly increased FDG uptake which reached 400% of baseline levels, whereas presence of glucose or serum decreased FDG uptake. Labeled cells were >90% viable for up to 22 hr, and the labeling process did appear to significantly activate cells, Washout studies however, demonstrated gradual washout of the FDG from monocytes after initial uptake PET images of FDG labeled monocytes in SD rats showed consistent findings. Utilizing insulin effects on cellular glucose metabolism may be a feasible way of labeling monocytes with 18 F-FDG for PET imaging. However, gradual washout of FDG after initial uptake poses as a potential problem which needs to be addressed before practical application

  11. Mycobacterium leprae upregulates IRGM expression in monocytes and monocyte-derived macrophages.

    Science.gov (United States)

    Yang, Degang; Chen, Jia; Zhang, Linglin; Cha, Zhanshan; Han, Song; Shi, Weiwei; Ding, Ru; Ma, Lan; Xiao, Hong; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-08-01

    Leprosy is caused by the infection of Mycobacterium leprae, which evokes a strong inflammatory response and leads to nerve damage. Immunity-related GTPase family M protein (IRGM) plays critical roles in controlling inflammation. The objective of the study was to investigate whether IRGM is involved in the infection of M. leprae. Levels of IRGM were assessed in M. leprae-infected CD4(+) T cells, monocytes, and monocyte-derived macrophages. Data revealed that both protein and mRNA levels of IRGM were increased in monocytes after M. leprae infection. Interestingly, monocyte-derived macrophages showed more prominent IRGM expression with M. leprae infection, whereas the bacteria did not affect IRGM in CD4(+) T cells. Furthermore, we assessed levels of IRGM in CD4(+) T cells and monocytes from 78 leprosy patients and 40 healthy controls, and observed upregulated protein level of IRGM in the monocytes from leprosy patients. Also, IRGM expression was inversely correlated with the severity of the disease. These findings suggested a close involvement of IRGM in M. leprae infection and indicated a potential mechanism of defending M. leprae infection.

  12. A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

    DEFF Research Database (Denmark)

    Royer, J F; Schratl, P; Lorenz, S

    2007-01-01

    developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release...... from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD......(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast...

  13. Immunophenotyping of eosinophils recovered from blood and BAL of allergic asthmatics

    NARCIS (Netherlands)

    Mengelers, H. J.; Maikoe, T.; Brinkman, L.; Hooibrink, B.; Lammers, J. W.; Koenderman, L.

    1994-01-01

    Studies of bronchoalveolar lavage (BAL) fluid from patients with allergic asthma have demonstrated active migration of eosinophils into the bronchial lumen after allergen challenge. The mechanisms mediating this eosinophil infiltration and cell activation are largely unexplained. The expression of

  14. Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo

    Science.gov (United States)

    Chu, Derek K.; Jimenez-Saiz, Rodrigo; Verschoor, Christopher P.; Walker, Tina D.; Goncharova, Susanna; Llop-Guevara, Alba; Shen, Pamela; Gordon, Melissa E.; Barra, Nicole G.; Bassett, Jennifer D.; Kong, Joshua; Fattouh, Ramzi; McCoy, Kathy D.; Bowdish, Dawn M.; Erjefält, Jonas S.; Pabst, Oliver; Humbles, Alison A.; Kolbeck, Roland; Waserman, Susan

    2014-01-01

    Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity. PMID:25071163

  15. TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.

    Directory of Open Access Journals (Sweden)

    Seung Jin Lee

    Full Text Available Toll-like receptor 4 (TLR4 is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA, a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.

  16. Monocyte chemotactic protein-4 (MCP-4/CCL-13) and CC ...

    African Journals Online (AJOL)

    EL-HAKIM

    chronic inflammation and local tissue eosinophilia. Atopic asthma is characterized by a 50-fold increase in the number of eosinophils relative to neutrophils in the bronchial mucosa. This is the result of the cumulative and sequential effects of variable increases in selective eosinophil versus neutrophil migration occurring at ...

  17. Canine eosinophilic folliculitis and furunculosis in three cases.

    Science.gov (United States)

    Curtis, C F; Bond, R; Blunden, A S; Thomson, D G; McNeil, P E; Whitbread, T W

    1995-03-01

    The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described. The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle. Skin lesions were confined to the face in two cases. The third dog had more generalised pustular lesions. Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units. Dermal collagen necrosis was evident in two cases. Similar facial lesions have previously been described as 'nasal pyoderma'. The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis. The aetiology of the disease was not determined.

  18. Eosinophilic Gastroenteritis Presenting as Intestinal Obstruction - A Case Series

    Directory of Open Access Journals (Sweden)

    Amita Krishnappa

    2011-07-01

    Full Text Available Eosinophilic Gastroenteritis is a rare disease characterized by infiltration of the gastrointestinal tract by an increased number of eosinophils as compared to the normal. The anatomic location and intensity of the infiltrate decides the varied clinical symptomatology with which these patients present. The present report deals with four cases, all presenting with clinical signs of intestinal obstruction A laparotomy performed revealed a stricture in the first case, superficial ulcers and adhesions in the second case, an ileocaecal mass in the third case and volvulus formation in the fourth case. Eosinophilic gastroenteritis was confirmed on histopathology in all the four cases. All the four patients experienced relief of symptoms after resection. It is essential to diagnose the disease to differentiate it from other conditions presenting as intestinal obstruction. The cases are presented because of the rarity of occurrence and presentation. Relevant literature has been reviewed.

  19. Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis.

    Science.gov (United States)

    Fujiyama, Toshiharu; Tokura, Yoshiki

    2013-06-01

    Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression-associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T-cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T-cell lymphoma resemble EPF. © 2013 Japanese Dermatological Association.

  20. X-ray and CT findings of costal eosinophilic granuloma

    International Nuclear Information System (INIS)

    Tu Zhanhai; Lin Zhengyu; Chen Yiguang

    2010-01-01

    Objective: To study the X-ray and CT features of costal eosinophilic granuloma for a better understanding. Methods: Eight patients with costal eosinophilic granuloma proved by surgery or biopsy were analyzed retrospectively. All patients had X-ray plain film, 6 patients had CT examination, including a case of enhanced CT scan. Results: All 8 lesions were solitary. Six lesions were in the anterior rib and 2 in the posterior rib. On X-ray, all case showed single cavity and oval lesion with clear boundary. On CT images, 5 lesions demonstrated expansile destruction of bone with cortical bone thinning, and 3 were osteolystic destruction with soft tissue mass around. On the patient with enhanced CT scan, the lesions showed a moderate and uniform enhancement. Conclusion: The X-ray and CT findings of costal eosinophilic granuloma are characteristic. (authors)

  1. The imaging diagnosis of costal solitary eosinophilic granuloma

    International Nuclear Information System (INIS)

    Cui Fa; Feng Shiting

    2007-01-01

    Objective: To study the imaging features of costal eosinophilic granuloma so as to improve diagnosis accuracy of the disease. Methods: The clinical and imaging materials of 6 patients with costal solitary eosinophilic granuloma which were proved by surgery or histopathology were analyzed retrospectively. X-ray plain films were performed in all the cases, CT in 3 cases, 2 cases were received CT plain scan and I case received both CT plain scan and enhanced CT scan. Results: 4 cases of them located in the anterior ribs. All the lesions were round-like and 5 were single cavity and 1 was multiple cavities. 3 of them were expansile destruction and 3 were cystic destruction. Soft tissue mass around the lesion was identified. Conclusion: X-ray plain films integrating CT play an important role in diagnosis and differential diagnosis of the costal eosinophilic granuloma. (authors)

  2. Case report 342: Eosinophilic granuloma of the right iliac wing

    International Nuclear Information System (INIS)

    Schlesinger, A.E.; Glass, R.B.J.; Fernbach, S.K.; Young, S.

    1986-01-01

    In summary, this case demonstrates that eosinophilic granuloma may present with findings on CT usually associated with aggressive malignant lesions, while plain films may show the same lesion to have the unequivocal appearance of a benign lesion. It is important, therefore, that eosinophilic granuloma be considered in the differential diagnosis of solitary bone lesions with extraosseous extension, extensive destruction of the cortex and associated periosteal reaction. A local biopsy, as opposed to wide excision, should be performed for diagnosis, prior to any therapy. Of at least equal significance, it is obvious from this case that plain films in many instances still maintain their importance and with few exceptions should be obtained prior to the CT study. In this instance the diagnosis of a benign disorder and even the specific diagnoses of eosinophilic, granuloma was suggested with confidence because of the plain films. (orig.)

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

    Science.gov (United States)

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

    2016-07-01

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

  4. Enterobiliary Fistula as a Complication of Eosinophilic Gastroenteritis: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Han Myun; Woo, Ji Young [Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2008-06-15

    Eosinophilic gastroenteritis is an uncommon disease with variable clinical features characterized by eosinophilic infiltration. Clinical manifestations range from non-specific gastrointestinal complaints such as nausea, vomiting, crampy abdominal pain, and diarrhea to specific findings such as malabsorption, protein loosing enteropathy, luminal obstruction, eosinophilic ascites and effusion. We report here on a case of eosinophilic gastroenteritis causing enterobiliary fistula which is an extremely unusual complication

  5. Enterobiliary Fistula as a Complication of Eosinophilic Gastroenteritis: a Case Report

    International Nuclear Information System (INIS)

    Kim, Han Myun; Woo, Ji Young

    2008-01-01

    Eosinophilic gastroenteritis is an uncommon disease with variable clinical features characterized by eosinophilic infiltration. Clinical manifestations range from non-specific gastrointestinal complaints such as nausea, vomiting, crampy abdominal pain, and diarrhea to specific findings such as malabsorption, protein loosing enteropathy, luminal obstruction, eosinophilic ascites and effusion. We report here on a case of eosinophilic gastroenteritis causing enterobiliary fistula which is an extremely unusual complication

  6. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... that may increase the risk of acute lymphocytic leukemia include: Previous cancer treatment. Children and adults who've had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased ... leukemia. Exposure to radiation. People exposed to very high ...

  7. Eosinophilic pleural effusion: incidence, etiology and prognostic significance.

    Science.gov (United States)

    Ferreiro, Lucía; San José, Esther; González-Barcala, Francisco Javier; Alvarez-Dobaño, José Manuel; Golpe, Antonio; Gude, Francisco; Anchorena, Christian; Pereyra, Marco F; Zamarrón, Carlos; Valdés, Luis

    2011-10-01

    Eosinophilic pleural effusion (EPE) has been associated with less risk for malignancy with a potential causal relationship with the presence of air and/or blood in the pleural space. However, these theories have fallen by the wayside in the light of recent publications. To determine the incidence and etiology of EPE and to observe whether the eosinophils in the pleural liquid (PL) increase in successive thoracocenteses. We analyzed 730 PL samples from 605 patients hospitalized between January 2004 and December 2010. We identified 55 samples with EPE from 50 patients (8.3%). The most frequent etiologies of EPE were: unknown (36%) and neoplasm (30%). There were no significant differences in the incidence of neoplasms between the non-eosinophilic pleural effusions (non-EPE) (25.9%) and the EPE (30%) (p=0.533). One hundred patients (16.5%) underwent a second thoracocentesis. Out of the 9 who had EPE in the first, 6 maintained EPE in the second. Out of the 91 with non-EPE in the first thoracocentesis, 8 (8.8%) had EPE in the repeat thoracocentesis. The percentage of eosinophils did not increase in the successive thoracocenteses (p=0.427). In the EPE, a significant correlation was found between the number of hematites and eosinophils in the PL (r=0.563; p=0.000). An EPE cannot be considered an indicator of benignancy, therefore it should be studied as any other pleural effusion. The number of eosinophils does not seem to increase with the of repetition of thoracocentesis and, lastly, the presence of blood in the PL could explain the existence of EPE. Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.

  8. Beta 2-adrenergic receptors on eosinophils. Binding and functional studies

    International Nuclear Information System (INIS)

    Yukawa, T.; Ukena, D.; Kroegel, C.; Chanez, P.; Dent, G.; Chung, K.F.; Barnes, P.J.

    1990-01-01

    We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand [125I]pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed

  9. Eosinophil count is positively correlated with coronary artery calcification

    International Nuclear Information System (INIS)

    Tanaka, Muhei; Fukui, Michiaki; Yamasaki, Masahiro; Hasegawa, Goji; Oda, Yohei; Nakamura, Naoto; Tomiyasu, Ki-ichiro; Akabame, Satoshi; Nakano, Koji

    2012-01-01

    Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C-reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log (CAC+1), respectively. Positive correlations were found between log (CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log (CAC+1) and eGFR (r=-0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (β=0.314, P<0.0001), sex (β=0.124, P<0.0001), hypertension (β=0.084, P=0.0008), DM (β=0.108, P<0.0001), eGFR (β=-0.079, P=0.0021) and eosinophil count (β=0.147, P<0.0001) were independent determinants of log (CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD. (author)

  10. Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcγ Receptors.

    Science.gov (United States)

    Smith, Kalmia M; Rahman, Raiann S; Spencer, Lisa A

    2016-11-01

    Eosinophils are native to the healthy gastrointestinal tract and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g., food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct Ag engagement elicits eosinophil effector functions, including degranulation and Ag presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food Ags by a columnar epithelium might similarly engage food Ags. Using an intestinal ligated loop model in mice, in this study we determined that resident intestinal eosinophils acquire Ag from the lumen of Ag-sensitized but not naive mice in vivo. Ag acquisition was Ig-dependent; intestinal eosinophils were unable to acquire Ag in sensitized Ig-deficient mice, and passive immunization with immune serum or Ag-specific IgG was sufficient to enable intestinal eosinophils in otherwise naive mice to acquire Ag in vivo. Intestinal eosinophils expressed low-affinity IgG receptors, and the activating receptor FcγRIII was necessary for Ig-mediated acquisition of Ags by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food Ags in sensitized mice via FcγRIII Ag focusing and that they may therefore participate in Ag-driven secondary immune responses to oral Ags. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. Emerging roles of eosinophils and eosinophil-derived lipid mediators in the resolution of inflammation

    Directory of Open Access Journals (Sweden)

    Yosuke eIsobe

    2012-08-01

    Full Text Available Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. Once thought to be a passive process, the resolution of inflammation is now shown to involve active biochemical programs that enable inflamed tissues to return to homeostasis. The mechanisms by which acute inflammation is resolved are of interest, and research in recent years has uncovered new endogenous anti-inflammatory and pro-resolving lipid mediators (i.e. lipoxins, resolvins, protectin, and maresin generated from polyunsaturated fatty acids (PUFAs. This review presents new insights into the cellular and molecular mechanisms of inflammatory resolution, especially the roles of eosinophils, and a series of omega-3 PUFA derived anti-inflammatory lipid mediators that they generate.

  12. A Case Report of Eosinophilic Esophagitis Accompanying Hypereosinophilic Syndrome

    Directory of Open Access Journals (Sweden)

    Mahreema Jawairia

    2012-01-01

    Full Text Available Hypereosinophilic syndrome is a blood disorder characterized by the overproduction of eosinophils in the bone marrow with persistent peripheral eosinophilia, associated with organ damage by the release of eosinophilic mediators. Although HES can involve multiple organ systems, GI tract involvement is very rare. Few cases of HES presenting with gastritis or enteritis have been reported worldwide. To date, HES presenting with esophagus involvement has only been reported once. Here, we present a 39-year-old Hispanic female patient with history of HES presenting with complaints of dysphagia and generalized pruritus.

  13. A pediatric case of Fascioliasis with eosinophilic pneumonia.

    Science.gov (United States)

    Bayhan, Gülsüm İclal; Batur, Abdulsamet; Taylan-Özkan, Ayşegül; Demirören, Kaan; Beyhan, Yunus Emre

    2016-01-01

    Fasciolia spp. are common trematode infestations worldwide. Fasciolia spp. may lead to hepatic diseases in the acute phase and may cause biliary diseases in the chronic phase. In addition, Fasciolia spp. may rarely cause extrahepatic signs and symptoms. The clinical manifestations of fascioliasis are divided into three groups: typical, atypical, and ectopic. Eosinophilic pneumonia is an atypical presentation of acute fascioliasis and it has been reported very rarely. Herein, we report a boy with marked blood eosinophilia and eosinophilic pneumonia who was diagnosed with fascioliasis by serologic tests and abdominal USG. The patient recovered completely following triclabendazole treatment.

  14. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    International Nuclear Information System (INIS)

    Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P.

    1991-01-01

    The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 x 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 ± 0.22 nM; Bmax1 = 966 ± 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 ± 8.9 nM; Bmax2 = 5557 ± 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of [3H]LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 ± 0.14 and 18.14 ± 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 x 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 x 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions

  15. BLOOD EOSINOPHIL NUMBERS AND ACTIVITY DURING 24 HOURS - EFFECTS OF TREATMENT WITH BUDESONIDE AND BAMBUTEROL

    NARCIS (Netherlands)

    WEMPE, JB; TAMMELING, EP; KOETER, GH; HAKANSSON, L; VENGE, P; POSTMA, DS

    1992-01-01

    The effects of the inhaled corticosteroid budesonide and the oral long-acting beta-agonist bambuterol on circadian variation of blood eosinophil numbers, serum levels of eosinophil cationic protein (ECP), serum eosinophil chemotactic activity (ECA), and serum neutrophil chemotactic activity (NCA)

  16. IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.

    Science.gov (United States)

    Hashiguchi, Masaaki; Kashiwakura, Yuji; Kojima, Hidefumi; Kobayashi, Ayano; Kanno, Yumiko; Kobata, Tetsuji

    2015-03-01

    Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. The proliferative human monocyte subpopulation contains osteoclast precursors

    Science.gov (United States)

    Lari, Roya; Kitchener, Peter D; Hamilton, John A

    2009-01-01

    Introduction Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors. Methods Human peripheral blood monocytes were sorted based upon their degree of proliferation and cultured in macrophage colony-stimulating factor (M-CSF or CSF-1) and receptor activator of nuclear factor-kappa-B ligand (RANKL). Results The monocyte subpopulation that is capable of proliferation gave rise to significantly more multinucleated, bone-resorbing osteoclasts than the bulk of the monocytes. Conclusions Human peripheral blood osteoclast precursors reside in the proliferative monocyte subpopulation. PMID:19222861

  18. Morphea and Eosinophilic Fasciitis: An Update.

    Science.gov (United States)

    Mertens, Jorre S; Seyger, Marieke M B; Thurlings, Rogier M; Radstake, Timothy R D J; de Jong, Elke M G J

    2017-08-01

    Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes

  19. Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis.

    Science.gov (United States)

    Petsky, Helen L; Cates, Chris J; Kew, Kayleigh M; Chang, Anne B

    2018-06-01

    Asthma guidelines guide health practitioners to adjust treatments to the minimum level required for asthma control. As many people with asthma have an eosinophilic endotype, tailoring asthma medications based on airway eosinophilic levels (sputum eosinophils or exhaled nitric oxide, FeNO) may improve asthma outcomes. To synthesise the evidence from our updated Cochrane systematic reviews, for tailoring asthma medication based on eosinophilic inflammatory markers (sputum analysis and FeNO) for improving asthma-related outcomes in children and adults. Cochrane reviews with standardised searches up to February 2017. The Cochrane reviews included randomised controlled comparisons of tailoring asthma medications based on sputum analysis or FeNO compared with controls (primarily clinical symptoms and/or spirometry/peak flow). The 16 included studies of FeNO-based management (seven in adults) and 6 of sputum-based management (five in adults) were clinically heterogeneous. On follow-up, participants randomised to the sputum eosinophils strategy (compared with controls) were significantly less likely to have exacerbations (62 vs 82/100 participants with ≥1 exacerbation; OR 0.36, 95% CI 0.21 to 0.62). For the FeNO strategy, the respective numbers were adults OR 0.60 (95% CI 0.43 to 0.84) and children 0.58 (95% CI 0.45 to 0.75). However, there were no significant group differences for either strategy on daily inhaled corticosteroids dose (at end of study), asthma control or lung function. Adjusting treatment based on airway eosinophilic markers reduced the likelihood of asthma exacerbations but had no significant impact on asthma control or lung function. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Lymphocytic Esophagitis: An emerging clinicopathologic disease associated with dysphagia

    Science.gov (United States)

    Pasricha, Sarina; Gupta, Amit; Reed, Craig C.; Speck, Olga; Woosley, John T.; Dellon, Evan S.

    2016-01-01

    Background Lymphocytic Esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. Aim To characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. Methods We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000 and June 1, 2012. Archived pathology slides were re-reviewed and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Results 27 adults were diagnosed with LyE, and the majority were female (63%). The most common symptom was dysphagia (70%). 52% had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37%), erosive esophagitis (33%), rings (26%), and hiatal hernia (26%); 33% of patients required dilation. After histology re-review, 78% of LyE patients were found to have more than 20 lymphs/hpf. In comparison to the normal, reflux and EoE controls, patients with LyE tended to be non-white (pdysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy. PMID:27343035

  1. Lymphocytic Esophagitis: An Emerging Clinicopathologic Disease Associated with Dysphagia.

    Science.gov (United States)

    Pasricha, Sarina; Gupta, Amit; Reed, Craig C; Speck, Olga; Woosley, John T; Dellon, Evan S

    2016-10-01

    Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy.

  2. Transcriptomic analysis of monocytes and macrophages derived from CLL patients which display differing abilities to respond to therapeutic antibody immune complexes

    Directory of Open Access Journals (Sweden)

    M. Burgess

    2016-03-01

    Full Text Available Chronic lymphocytic leukemia (CLL is the most common adult leukemia. While therapeutic antibodies show clinical activity in CLL patients, resistance inevitably develops resulting in treatment failure. Identifying mechanisms of antibody resistance and methods to reduce resistance would be valuable in managing CLL. Monocyte derived cells (MDCs, also known as nurse like cells (NLCs in CLL [1,2], are known to be crucial components of the CLL microenvironment network and following “maturation” in in vitro culture systems are able to provide support for the survival of the malignant B cells from CLL patients. In addition to their protective role, MDCs are key effector cells in mediating responses to therapeutic antibody therapies [3]. We have determined that macrophages from patients with early stable CLL are able to elicit superior cytotoxic response to therapeutic antibodies than macrophages derived from patients with progressive CLL. We have exploited this unique finding to gain insight into antibody resistance. Thus, we have profiled monocytes on day 0 and MDCs on day 7 from antibody sensitive and antibody resistant CLL patients (GEO accession number GEO: GSE71409. We show that there are no significant differences in transcriptomes from the monocytes or MDCs derived from sensitive or resistant patient samples. However, we show that MDCs acquire an M2-like macrophage transcriptomic signature following 7 days culture regardless of whether they were derived from sensitive or resistant patient samples. Keywords: Chronic lymphocytic leukemia, Monocyte derived cells, Antibody resistance, Microarray

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

    Science.gov (United States)

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

    2018-06-08

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

  4. Statins attenuate polymethylmethacrylate-mediated monocyte activation.

    LENUS (Irish Health Repository)

    Laing, Alan J

    2012-02-03

    BACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte\\/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

  5. Eosinophilic Gastrointestinal Disorder in Coeliac Disease: A Case Report and Review

    Directory of Open Access Journals (Sweden)

    Dennis N. F. Lim

    2012-01-01

    Full Text Available Eosinophilic gastrointestinal disorder is a rare disorder characterised by eosinophilic infiltration of the gastrointestinal tract. There are various gastrointestinal manifestations with eosinophilic ascites being the most unusual and rare presentation. Diagnosis requires high index of suspicion and exclusion of various disorders associated with peripheral eosinophilia. There are no previous case reports to suggest an association between eosinophilic gastrointestinal disorder and coeliac disease in adults. We report a case of eosinophilic ascites and gastroenteritis in a 30-year-old woman with a known history of coeliac disease who responded dramatically to a course of steroids.

  6. Detection of eosinophil cationic protein (ECP) by an enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Reimert, C M; Venge, P; Kharazmi, A

    1991-01-01

    Eosinophil cationic protein (ECP) is a highly basic and potent cytotoxic single-chain zinc-containing protein present in the granules of the eosinophilic granulocytes. ECP appears to be involved in defence against parasites and in the tissue damage seen in subjects with allergic and inflammatory...... disease. To investigate ECP release from in vitro activated human eosinophils and to study the involvement of eosinophils in health and disease, we have developed a sensitive and specific enzyme immunoassay. ECP was purified from normal human peripheral blood eosinophils and polyclonal antibodies to ECP...

  7. Non-allergic activation of eosinophils after strenuous endurance ...

    African Journals Online (AJOL)

    Objective. To determine the effect of prolonged endurance exercise on the serum concentrations of eosinophil cationic protein (ECP), immunoglobulin E (IgE) and upper respiratory tract symptoms (URTS). Design. In 11 healthy, experienced volunteers (6 males, 5 females, age 43 ± 9.8 years) the serum concentrations of ...

  8. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

    NARCIS (Netherlands)

    Cottin, Vincent; Bel, Elisabeth; Bottero, Paolo; Dalhoff, Klaus; Humbert, Marc; Lazor, Romain; Sinico, Renato A.; Sivasothy, Pasupathy; Wechsler, Michael E.; Groh, Matthieu; Marchand-Adam, Sylvain; Khouatra, Chahéra; Wallaert, Benoit; Taillé, Camille; Delaval, Philippe; Cadranel, Jacques; Bonniaud, Philippe; Prévot, Grégoire; Hirschi, Sandrine; Gondouin, Anne; Dunogué, Bertrand; Chatté, Gérard; Briault, Amandine; Jayne, David; Guillevin, Loïc; Cordier, Jean-François

    2016-01-01

    The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail.In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease.The study

  9. A Case of Eosinophilic Pneumonia in a Tobacco Harvester

    Directory of Open Access Journals (Sweden)

    Daisuke Yoshioka

    2011-01-01

    Discussion: Green tobacco sickness, a type of nicotine poisoning caused by the dermal absorption of nicotine, is a well known occupational illness of tobacco harvesters. Although it is unclear whether the present case could be identified as a subtype of green tobacco sickness, this is the first report of eosinophilic pneumonia occurred in a tobacco harvester which was possibly induced by tobacco leaf exposure.

  10. Eosinophilic granuloma in jaw bone: a pare pediatric case report ...

    African Journals Online (AJOL)

    Background: Eosinophilic granuloma (EG), one of the three clinical forms of Langerhans cell histiocytosis (LCH), is a benign inflammatory reaction to an unknown etiologic agent. It most commonly occurs in children and young adults. The most frequently involved bones are the skull, the ribs and the femurs. Alongside the ...

  11. Racial differences in eosinophilic gastrointestinal disorders among Caucasian and Asian

    Directory of Open Access Journals (Sweden)

    Jun Ito

    2015-07-01

    Conclusions: We found that EoE occurs more frequently in Caucasian EGID patients than Asian EGID patients, while the reverse is true for EGE. Also, racial disparities in symptoms and eosinophil-infiltrated tissues were observed. Our findings suggest further genetic and environmental studies to elucidate the etiology of EGID.

  12. Eosinophilic enteritis – A diagnostic dilemma | Clegg-Lamptey ...

    African Journals Online (AJOL)

    It may mimic peptic ulcer, subacute (or chronic) intestinal obstruction, gastroenteritis, irritable bowel syndrome, and inflammatory bowel disease. The diagnosis is often ... Finalement laparotomy a revele des segments enflames de petit intestin, une biopsie de qui a montré Eosinophilic enteritis. Le malade a été traite par la ...

  13. Pediatric eosinophilic esophagitis: radiologic findings with pathologic correlation

    International Nuclear Information System (INIS)

    Binkovitz, Larry A.; Lorenz, Emily A.; Di Lorenzo, Carlo; Kahwash, Samir

    2010-01-01

    Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia or food impaction in pediatric patients. It has a high male predominance and is often associated with a history of allergy or asthma. To correlate fluoroscopic findings in eosinophilic esophagitis with the endoscopic and histologic findings. We retrospectively reviewed the upper gastrointestinal (UGI) findings of eosinophilic esophagitis and correlated them with the clinical, endoscopic and histologic findings in a series of 17 children (12 boys, 5 girls). UGI findings were normal in 12 children, including 4 who had a normal UGI exam after endoscopic disimpaction for an obstructing food bolus. Five children had strictures identified on UGI: one was demonstrated with endoscopy. This suggests that the impactions and strictures were due to an esophageal dysmotility rather than a fixed anatomic abnormality. Because the UGI findings are frequently normal in eosinophilic esophagitis, radiologists need to have a high index of suspicion for this disease. In children with a strong clinical history, especially impaction in the absence of an esophageal stricture, endoscopy and biopsy are indicated for further evaluation. (orig.)

  14. Pediatric eosinophilic esophagitis: radiologic findings with pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Binkovitz, Larry A. [Nationwide Children' s Hospital, Columbus, OH (United States); Mayo Clinic, Division of Pediatric Radiology, E-2, Rochester, MN (United States); Lorenz, Emily A. [Nationwide Children' s Hospital, Columbus, OH (United States); Di Lorenzo, Carlo [Nationwide Children' s Hospital, Department of Gastroenterology, Columbus, OH (United States); Kahwash, Samir [Nationwide Children' s Hospital, Department of Pathology, Columbus, OH (United States)

    2010-05-15

    Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia or food impaction in pediatric patients. It has a high male predominance and is often associated with a history of allergy or asthma. To correlate fluoroscopic findings in eosinophilic esophagitis with the endoscopic and histologic findings. We retrospectively reviewed the upper gastrointestinal (UGI) findings of eosinophilic esophagitis and correlated them with the clinical, endoscopic and histologic findings in a series of 17 children (12 boys, 5 girls). UGI findings were normal in 12 children, including 4 who had a normal UGI exam after endoscopic disimpaction for an obstructing food bolus. Five children had strictures identified on UGI: one was demonstrated with endoscopy. This suggests that the impactions and strictures were due to an esophageal dysmotility rather than a fixed anatomic abnormality. Because the UGI findings are frequently normal in eosinophilic esophagitis, radiologists need to have a high index of suspicion for this disease. In children with a strong clinical history, especially impaction in the absence of an esophageal stricture, endoscopy and biopsy are indicated for further evaluation. (orig.)

  15. Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype, or clinical status

    International Nuclear Information System (INIS)

    Han, T.; Bloom, M.L.; Dadey, B.; Bennett, G.; Minowada, J.; Sandberg, A.A.; Ozer, H.

    1982-01-01

    In the present study, there was a complete lack of autologous MLR between responding T cells or T subsets and unirradiated or irradiated leukemic B cells or monocytes in all 20 patients with CLL, regardless of disease status, stage, phenotype, or karyotype of the disease. The stimulating capacity of unirradiated CLL B cells and CLL monocytes or irradiated CLL B cells was significantly depressed as compared to that of respective normal B cells and monocytes in allogeneic MLR. The responding capacity of CLL T cells was also variably lower than that of normal T cells against unirradiated or irradiated normal allogeneic B cells and monocytes. The depressed allogeneic MLR between CLL B cells or CLL monocytes and normal T cells described in the present study could be explained on the basis of a defect in the stimulating antigens of leukemic B cells or monocytes. The decreased allogeneic MLR of CLL T cells might simply be explained by a defect in the responsiveness of T lymphocytes from patients with CLL. However, these speculations do not adequately explain the complete lack of autologous MLR in these patients. When irradiated CLL B cells or irradiated CLL T cells were cocultured with normal T cells and irradiated normal B cells, it was found that there was no suppressor cell activity of CLL B cells or CLL T cells on normal autologous MLR. Our data suggest that the absence or dysfunction of autoreactive T cells within the Tnon-gamma subset account for the lack of autologous MLR in patients with CLL. The possible significance of the autologous MLR, its relationship to in vivo immunoregulatory mechanisms, and the possible role of breakdown of autoimmunoregulation in the oncogenic process of certain lymphoproliferative and autoimmune diseases in man are discussed

  16. Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.

    LENUS (Irish Health Repository)

    Walsh, Marie-Therese

    2011-11-01

    Eosinophils exert many of their inflammatory effects in allergic disorders through the degranulation and release of intracellular mediators, including a set of cationic granule proteins that include eosinophil peroxidase. Studies suggest that eosinophils are involved in remodeling. In previous studies, we showed that eosinophil granule proteins activate mitogen-activated protein kinase signaling. In this study, we investigated the receptor mediating eosinophil peroxidase-induced signaling and downstream effects. Human cholinergic neuroblastoma IMR32 and murine melanoma B16.F10 cultures, real-time polymerase chain reaction, immunoprecipitations, and Western blotting were used in the study. We showed that eosinophil peroxidase caused a sustained increase in both the expression of epidermal growth factor-2 (HER2) and its phosphorylation at tyrosine 1248, with the consequent activation of extracellular-regulated kinase 1\\/2. This, in turn, promoted a focal adhesion kinase-dependent egress of the cyclin-dependent kinase inhibitor p27(kip) from the nucleus to the cytoplasm. Eosinophil peroxidase induced a HER2-dependent up-regulation of cell proliferation, indicated by an up-regulation of the nuclear proliferation marker Ki67. This study identifies HER2 as a novel mediator of eosinophil peroxidase signaling. The results show that eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation, and contribute to tissue remodeling and cell turnover in airway disease. Because eosinophils are a feature of many cancers, these findings also suggest a role for eosinophils in tumorigenesis.

  17. Eosinophilic esophagitis: an Italian experience Esofagitis eosinofílica: una experiencia italiana

    Directory of Open Access Journals (Sweden)

    C. Vindigni

    2010-01-01

    Full Text Available Background: eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. Aims: the purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. Patients and methods: we retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. Results: twenty two patients (14 adults, 8 children, age range 2-59 years were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31-150, associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation. The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. Conclusions: eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries.

  18. Increased eosinophil activity in acute Plasmodium falciparum infection - association with cerebral malaria

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Reimert, C M; Tette, E

    1998-01-01

    To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven...... of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness...... followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM...

  19. Case series of eosinophilic meningoencephalitis from South India

    Directory of Open Access Journals (Sweden)

    Parameswaran K

    2006-01-01

    Full Text Available Eosinophilic meningoencephalitis (EM is a rare type of meningoencephalitis. The objective of this report is to describe a series of EM identified in a specific geographic area over a short period of time. Materials and Methods: This series of cases are described from a neurological center in Central Kerala occuring in the period between February 2004 and June 2006. Results: During this period we had identified ten patients (eight males and two females with EM. Their mean age was 37.1 years (range 15-60 years. Main symptomatologies were fever, severe headache, body pain, abdominal pain and arthralgia. One patient was in akinetic rigid state with coma. All patients had peripheral eosinophilia. The cerebrospinal fluid (CSF of all patients showed eosinophilic pleocytosis. The mean CSF white cell count was 588 cells. CSF differential count showed 50-70% eosinophils. CSF glucose levels were normal but proteins were markedly raised (mean CSF protein was 180 mg/dl. MRI brain showed T2 hyperintensities diffusely in periventricular white matter in the comatose patient. Contrast enhanced CT scan of the brain was normal in others. All eight male patients gave history of eating "raw flesh of Monitor Lizard" (Iguana some three to fourteen days prior to the onset of symptoms. There was no such history for the female patients. Considering the history of exposure and eosinophilic meningitis we suspected a meningoencephalitis with Angiostrongylus cantonensis and treated them with albendazole, steroid and other supportive measures. All of them recovered. Conclusion: Eosinophilic meningitis (EM is a rare condition and in this locality, a CNS infection with Agiostrongylus cantonensis is highly likely. AC is a parasite in monitor lizard. Human infection occurs from consumption of uncooked flesh or blood of infected lizards. Physicians need to maintain a high index of suspicion and enquire for any exposure to uncooked meat or blood of monitor lizard when faced with EM

  20. A Pilot Study of Omalizumab in Eosinophilic Esophagitis

    Science.gov (United States)

    Loizou, Denise; Enav, Benjamin; Komlodi-Pasztor, Edina; Hider, Pamela; Kim-Chang, Julie; Noonan, Laura; Taber, Tabitha; Kaushal, Suhasini; Limgala, Renuka; Brown, Margaret; Gupta, Raavi; Balba, Nader; Goker-Alpan, Ozlem; Khojah, Amer; Alpan, Oral

    2015-01-01

    Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE), once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE) levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy. Trial Registration ClinicalTrials.gov NCT01040598 PMID:25789989

  1. A pilot study of omalizumab in eosinophilic esophagitis.

    Directory of Open Access Journals (Sweden)

    Denise Loizou

    Full Text Available Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE, once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy.

  2. Urinary Eosinophil Protein X in Childhood Asthma : Relation with Changes in Disease Control and Eosinophilic Airway Inflammation

    NARCIS (Netherlands)

    Nuijsink, Marianne; Hop, Wim C. J.; Sterk, Peter J.; Duiverman, Eric J.; De Jongste, Johan C.

    2013-01-01

    The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation. Methods. We measured uEPX at baseline, after 1 year and after 2 years in 205 atopic asthmatic children using inhaled fluticasone.

  3. Urinary eosinophil protein X in childhood asthma: relation with changes in disease control and eosinophilic airway inflammation

    NARCIS (Netherlands)

    Nuijsink, Marianne; Hop, Wim C. J.; Sterk, Peter J.; Duiverman, Eric J.; de Jongste, Johan C.

    2013-01-01

    The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation. Methods. We measured uEPX at baseline, after 1 year and after 2 years in 205 atopic asthmatic children using inhaled fluticasone.

  4. Use of an adaptable cell culture kit for performing lymphocyte and monocyte cell cultures in microgravity

    Science.gov (United States)

    Hatton, J. P.; Lewis, M. L.; Roquefeuil, S. B.; Chaput, D.; Cazenave, J. P.; Schmitt, D. A.

    1998-01-01

    The results of experiments performed in recent years on board facilities such as the Space Shuttle/Spacelab have demonstrated that many cell systems, ranging from simple bacteria to mammalian cells, are sensitive to the microgravity environment, suggesting gravity affects fundamental cellular processes. However, performing well-controlled experiments aboard spacecraft offers unique challenges to the cell biologist. Although systems such as the European 'Biorack' provide generic experiment facilities including an incubator, on-board 1-g reference centrifuge, and contained area for manipulations, the experimenter must still establish a system for performing cell culture experiments that is compatible with the constraints of spaceflight. Two different cell culture kits developed by the French Space Agency, CNES, were recently used to perform a series of experiments during four flights of the 'Biorack' facility aboard the Space Shuttle. The first unit, Generic Cell Activation Kit 1 (GCAK-1), contains six separate culture units per cassette, each consisting of a culture chamber, activator chamber, filtration system (permitting separation of cells from supernatant in-flight), injection port, and supernatant collection chamber. The second unit (GCAK-2) also contains six separate culture units, including a culture, activator, and fixation chambers. Both hardware units permit relatively complex cell culture manipulations without extensive use of spacecraft resources (crew time, volume, mass, power), or the need for excessive safety measures. Possible operations include stimulation of cultures with activators, separation of cells from supernatant, fixation/lysis, manipulation of radiolabelled reagents, and medium exchange. Investigations performed aboard the Space Shuttle in six different experiments used Jurkat, purified T-cells or U937 cells, the results of which are reported separately. We report here the behaviour of Jurkat and U937 cells in the GCAK hardware in ground-based investigations simulating the conditions expected in the flight experiment. Several parameters including cell concentration, time between cell loading and activation, and storage temperature on cell survival were examined to characterise cell response and optimise the experiments to be flown aboard the Space Shuttle. Results indicate that the objectives of the experiments could be met with delays up to 5 days between cell loading into the hardware and initial in flight experiment activation, without the need for medium exchange. Experiment hardware of this kind, which is adaptable to a wide range of cell types and can be easily interfaced to different spacecraft facilities, offers the possibility for a wide range of experimenters successfully and easily to utilise future flight opportunities.

  5. Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice.

    Science.gov (United States)

    Jacobsen, E A; Doyle, A D; Colbert, D C; Zellner, K R; Protheroe, C A; LeSuer, W E; Lee, N A; Lee, J J

    2015-09-01

    Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Wild-type or cytokine-deficient (IL-13(-/-) or IL-4(-/-) ) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4(+) T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4(+) T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

    Science.gov (United States)

    Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

    2017-06-01

    Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright

  7. EMMPRIN (CD147/basigin) mediates platelet-monocyte interactions in vivo and augments monocyte recruitment to the vascular wall.

    Science.gov (United States)

    Schulz, C; von Brühl, M-L; Barocke, V; Cullen, P; Mayer, K; Okrojek, R; Steinhart, A; Ahmad, Z; Kremmer, E; Nieswandt, B; Frampton, J; Massberg, S; Schmidt, R

    2011-05-01

    Platelets play a central role in hemostasis, in inflammatory diseases such as atherosclerosis, and during thrombus formation following vascular injury. Thereby, platelets interact intensively with monocytes and enhance their recruitment to the vascular wall. To investigate the role of the extracellular matrix metalloproteinase inducer (EMMPRIN) in platelet-monocyte interactions. Isolated human monocytes were perfused in vitro over firmly adherent platelets to allow investigation of the role of EMMPRIN in platelet-monocyte interactions under flow conditions. Monocytes readily bound to surface-adherent platelets. Both antibody blockade and gene silencing of monocyte EMMPRIN substantially attenuated firm adhesion of monocytes to platelets at arterial and venous shear rates. In vivo, platelet interactions with the murine monocyte cell line ANA-1 were significantly decreased when ANA-1 cells were pretreated with EMMPRIN-silencing small interfering RNA prior to injection into wild-type mice. Using intravital microscopy, we showed that recruitment of EMMPRIN-silenced ANA-1 to the injured carotid artery was significantly reduced as compared with control cells. Further silencing of EMMPRIN resulted in significantly fewer ANA-1-platelet aggregates in the mouse circulation as determined by flow cytometry. Finally, we identified glycoprotein (GP)VI as a critical corresponding receptor on platelets that mediates interaction with monocyte EMMPRIN. Thus, blocking of GPVI inhibited the effect of EMMPRIN on firm monocyte adhesion to platelets under arterial flow conditions in vitro, and abrogated EMMPRIN-mediated platelet-monocyte aggregate formation in vivo. EMMPRIN supports platelet-monocyte interactions and promotes monocyte recruitment to the arterial wall. Therefore, EMMPRIN might represent a novel target to reduce vascular inflammation and atherosclerotic lesion development. © 2011 International Society on Thrombosis and Haemostasis.

  8. Glucocorticoid suppression of human lymphocyte DNA synthesis. Influence of phytohemagglutinin concentration

    International Nuclear Information System (INIS)

    Segel, G.B.; Lukacher, A.; Gordon, B.R.; Lichtman, M.A.

    1980-01-01

    Glucocorticoids have been shown to suppress lectin-stimulated lymphocyte DNA synthesis in some studies, whereas in other studies, the hormones have had little effect. We have found that the position on the PHA dose-response curve that is studied is the most important determinant of whether cortisol inhibits 3 H-thymidine incorporation into lymphocyte DNA. The proportion of monocytes in culture also influenced the cortisol effect, but it was quantitatively less important than PHA concentration. Cortisol (5 nM to 100 μM) had little effect on blastogenesis or thymidine incorporation into DNA in cultures that contained both a high concentration (14% +- 2 (S.E.)) of monocytes and a concentration of PHA (0.6 to 1.2 μg/ml) that produced maximal stimulation of mitogenesis. When monocytes were reduced from 14 to 1.4%, cortisol (5 μM) caused a 30% reduction in thymidine incorporation in cultures stimulated by 0.6 to 1.2 μg/ml PHA. Much greater cortisol suppression of thymidine incorporation occurred if the concentration of PHA was reduced. For example, reduction of the PHA concentration from 1.2 to 0.075 μg/ml resulted in an increase in suppression by 5 μM cortisol from 5 to 90% even in the presence of 14% monocytes. These data indicate that the suppressive effects of glucocorticoids on blastogenesis and thymidine incorporation in vitro depend principally on the concentration of PHA used to stimulate blastogenesis and secondarily on the proportion of monocytes in the culture system

  9. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2018-01-26

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  10. Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

    Directory of Open Access Journals (Sweden)

    Hohlfeld Reinhard

    2011-10-01

    Full Text Available Abstract Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS and neuromyelitis optica (NMO generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods Myelin oligodendrocyte glycoprotein (MOG peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg and cytokine production of CD11b+ antigen presenting cells (APC were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM. Results We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and

  11. Radiosensitivities of sensitized lymphocytes

    International Nuclear Information System (INIS)

    Taniguchi, Kazuto

    1979-01-01

    Immunization of mice with cell antigens such as allogeneic tumor cells or xenogeneic erythrocytes raises a variety of immune reactions mediated by T lymphocytes: i.e. delayed type hypersensitivity (DTH), cytotoxicity, and antibody production. The radiosensitivities of these reactions were examined in mice exposed to 600 R x-irradiation a few hours before or after immunization. 1) DTH to xenogeneic erythrocytes, as demonstrated by footpad reaction, was not suppressed by irradiation 3 h before or after immunization. DTH to allogeneic tumor cells, as demonstrated by a migration inhibition test, hardly developed in mice that had been irradiated before or after immunization. It may have belonged to distinct types of delayed reactions which were mediated by distinct subpopulations of T lymphocytes. 2) Cytotoxicity against allogeneic cells and xenogeneic erythrocytes showed almost the same radiosensitivity. It was scarcely detected in mice that had been irradiated before immunization. However, a low but definite degree of cytotoxicity was detected in mice that had been irradiated only a few hours after immunization. Solubilized allogeneic cells instead of native cells were used as immunizing antigens. It was also possible for precursor cells with cytotoxicity to acquire a radioresistant nature by immunization of solubilized antigens, but native cells were required as stimulation for radioresistant precursor cells to differentiated into nature cytotoxic effector cells. 3) Antibody production against xenogeneic erythrocytes or allogeneic cells was almost completely depleted in mice that had been irradiated before or after immunization. It is possible that antibody production essentially requires cell division and clonal expansion of B lymphocytes. (Bell, E.)

  12. Abnormal monocyte recruitment and collateral artery formation in monocyte chemoattractant protein-1 deficient mice

    NARCIS (Netherlands)

    Voskuil, Michiel; Hoefer, Imo E.; van Royen, Niels; Hua, Jing; de Graaf, Stijn; Bode, Christoph; Buschmann, Ivo R.; Piek, Jan J.

    2004-01-01

    Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of collateral artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of collateral

  13. Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

    Directory of Open Access Journals (Sweden)

    Harissios Vliagoftis

    2014-01-01

    Full Text Available Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

  14. Proton channel HVCN1 is required for effector functions of mouse eosinophils

    Science.gov (United States)

    2013-01-01

    Background Proton currents are required for optimal respiratory burst in phagocytes. Recently, HVCN1 was identified as the molecule required for the voltage-gated proton channel activity associated with the respiratory burst in neutrophils. Although there are similarities between eosinophils and neutrophils regarding their mechanism for respiratory burst, the role of proton channels in eosinophil functions has not been fully understood. Results In the present study, we first identified the expression of the proton channel HVCN1 in mouse eosinophils. Furthermore, using HVCN1-deficient eosinophils, we demonstrated important cell-specific effector functions for HVCN1. Similar to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils produced significantly less reactive oxygen species (ROS) upon phorbol myristate acetate (PMA) stimulation compared with WT eosinophils. In contrast to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils did not show impaired calcium mobilization or migration ability compared with wild-type (WT) cells. Uniquely, HVCN1-deficient eosinophils underwent significantly increased cell death induced by PMA stimulation compared with WT eosinophils. The increased cell death was dependent on NADPH oxidase activation, and correlated with the failure of HVCN1-deficient cells to maintain membrane polarization and intracellular pH in the physiological range upon activation. Conclusions Eosinophils require proton channel HVCN1 for optimal ROS generation and prevention of activation-induced cell death. PMID:23705768

  15. Asthma Control and Sputum Eosinophils: A Longitudinal Study in Daily Practice.

    Science.gov (United States)

    Demarche, Sophie F; Schleich, Florence N; Paulus, Virginie A; Henket, Monique A; Van Hees, Thierry J; Louis, Renaud E

    Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice. To investigate the relationship between asthma control and sputum eosinophils in clinical practice. A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values. A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort. At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.

    Science.gov (United States)

    Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D; Miyasaka, Masayuki; Yang, Bo-Gie; Jang, Myoung Ho

    2016-04-04

    Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. © 2016 Sugawara et al.

  17. Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils.

    Science.gov (United States)

    Tamaki, Mami; Konno, Yasunori; Kobayashi, Yoshiki; Takeda, Masahide; Itoga, Masamichi; Moritoki, Yuki; Oyamada, Hajime; Kayaba, Hiroyuki; Chihara, Junichi; Ueki, Shigeharu

    2014-07-01

    Sexual dimorphism in asthma links the estrogen and allergic immune responses. The function of estrogen was classically believed to be mediated through its nuclear receptors, i.e., estrogen receptors (ERs). However, recent studies established the important roles of G-protein-coupled estrogen receptor (GPER/GPR30) as a novel membrane receptor for estrogen. To date, the role of GPER in allergic inflammation is poorly understood. The purpose of this study was to examine whether GPER might affect the functions of eosinophils, which play an important role in the pathogenesis of asthma. Here, we demonstrated that GPER was expressed in purified human peripheral blood eosinophils both at the mRNA and protein levels. Although GPER agonist G-1 did not induce eosinophil chemotaxis or chemokinesis, preincubation with G-1 enhanced eotaxin (CCL11)-directed eosinophil chemotaxis. G-1 inhibited eosinophil spontaneous apoptosis and caspase-3 activities. The anti-apoptotic effect was not affected by the cAMP-phospodiesterase inhibitor rolipram or phosphoinositide 3-kinase inhibitors. In contrast to resting eosinophils, G-1 induced apoptosis and increased caspase-3 activities when eosinophils were co-stimulated with IL-5. No effect of G-1 was observed on eosinophil degranulation in terms of release of eosinophil-derived neurotoxin (EDN). The current study indicates the functional capacities of GPER on human eosinophils and also provides the previously unrecognized mechanisms of interaction between estrogen and allergic inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Eosinophilic gastroenteritis with Splendore-Hoeppli material in the ferret (Mustela putorius furo).

    Science.gov (United States)

    Fox, J G; Palley, L S; Rose, R

    1992-01-01

    Eosinophilic gastroenteritis, focal or diffuse with eosinophilic infiltrations of the stomach or intestine, has been described in human beings, cats, dogs, and horses. In this paper, we describe infiltration of the gastrointestinal tract with eosinophils accompanied by a circulating eosinophilia in six ferrets (Mustela putorius furo). Clinical signs included chronic weight loss, anorexia, and diarrhea. The small intestines from five ferrets had diffuse infiltrates of eosinophils. This resulted in focal or multifocal loss of the muscular tunic in three ferrets. Two of these ferrets also had eosinophilic gastritis. Eosinophilic granulomas with Splendore-Hoeppli material were present in mesenteric lymph nodes in four ferrets. Two ferrets had multiple organ involvement; one had eosinophilic granulomas in the liver, mesentery, and choroid plexus as well as moderate parapancreatic segmental arteritis with infiltration of eosinophils and mural thrombosis. The second ferret had, in addition to moderate diffuse gastric and small intestinal eosinophilic mucosal infiltrations, interstitial eosinophilic pulmonary infiltrates. Examination of all tissues failed to reveal an infectious agent.

  19. Assessment of Schistosoma mansoni induced intestinal inflammation by means of eosinophil cationic protein, eosinophil protein X and myeloperoxidase before and after treatment with praziquantel

    DEFF Research Database (Denmark)

    Reimert, Claus Michael; Tukahebwa, Edridah M.; Kabatereine, Narcis B.

    2008-01-01

    Faecal concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO) were measured in extracts of stool samples obtained from a cohort of people (n=182) living in Bugoigo, a fishing community on the Eastern shore of Lake Albert, Buliisa District, in North...

  20. Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

    Science.gov (United States)

    Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

    2015-01-01

    Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

  1. Eosinophils as a novel cell source of prostaglandin D2: autocrine role in allergic inflammation

    Science.gov (United States)

    Luna-Gomes, Tatiana; Magalhães, Kelly G; Mesquita-Santos, Fabio P.; Bakker-Abreu, Ilka; Samico, Rafaela F.; Molinaro, Raphael; Calheiros, Andrea S.; Diaz, Bruno L.; Bozza, Patrícia T.

    2011-01-01

    Prostaglandin (PG)D2 is a key mediator of allergic inflammatory diseases that is mainly synthesized by mast cells, which constitutively express high levels of the terminal enzyme involved in PGD2 synthesis, the hematopoietic PGD synthase (H-PGDS). Here, we investigated whether eosinophils are also able to synthesize, and therefore, supply biologically active PGD2. PGD2 synthesis was evaluated within human blood eosinophils, in vitro-differentiated mouse eosinophils, and eosinophils infiltrating inflammatory site of mouse allergic reaction. Biological function of eosinophil-derived PGD2 was studied by employing inhibitors of synthesis and activity. Constitutive expression of H-PGDS was found within non-stimulated human circulating eosinophils. Acute stimulation of human eosinophils with A23187 (0.1 – 5 μM) evoked PGD2 synthesis, which was located at the nuclear envelope and was inhibited by pre-treatment with HQL-79 (10 μM), a specific H-PGDS inhibitor. Pre-stimulation of human eosinophils with arachidonic acid (AA; 10 μM) or human eotaxin (6 nM) also enhanced HQL-79-sensitive PGD2 synthesis, which, by acting on membrane-expressed specific receptors (DP1 and DP2), displayed an autocrine/paracrine ability to trigger leukotriene (LT)C4 synthesis and lipid body biogenesis, hallmark events of eosinophil activation. In vitro-differentiated mouse eosinophils also synthesized paracrine/autocrine active PGD2 in response to AA stimulation. In vivo, at late time point of the allergic reaction, infiltrating eosinophils found at the inflammatory site appeared as an auxiliary PGD2-synthesizing cell population. Our findings reveal that eosinophils are indeed able to synthesize and secrete PGD2, hence representing during allergic inflammation an extra cell source of PGD2, which functions as an autocrine signal for eosinophil activation. PMID:22102725

  2. Hematopoietic Overexpression of FOG1 Does Not Affect B-Cells but Reduces the Number of Circulating Eosinophils

    Science.gov (United States)

    Du Roure, Camille; Versavel, Aude; Doll, Thierry; Cao, Chun; Pillonel, Vincent; Matthias, Gabriele; Kaller, Markus; Spetz, Jean-François; Kopp, Patrick; Kohler, Hubertus; Müller, Matthias; Matthias, Patrick

    2014-01-01

    We have identified expression of the gene encoding the transcriptional coactivator FOG-1 (Friend of GATA-1; Zfpm1, Zinc finger protein multitype 1) in B lymphocytes. We found that FOG-1 expression is directly or indirectly dependent on the B cell-specific coactivator OBF-1 and that it is modulated during B cell development: expression is observed in early but not in late stages of B cell development. To directly test in vivo the role of FOG-1 in B lymphocytes, we developed a novel embryonic stem cell recombination system. For this, we combined homologous recombination with the FLP recombinase activity to rapidly generate embryonic stem cell lines carrying a Cre-inducible transgene at the Rosa26 locus. Using this system, we successfully generated transgenic mice where FOG-1 is conditionally overexpressed in mature B-cells or in the entire hematopoietic system. While overexpression of FOG-1 in B cells did not significantly affect B cell development or function, we found that enforced expression of FOG-1 throughout all hematopoietic lineages led to a reduction in the number of circulating eosinophils, confirming and extending to mammals the known function of FOG-1 in this lineage. PMID:24747299

  3. T-helper 2 cytokines, transforming growth factor β1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis.

    Science.gov (United States)

    Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

    2014-05-01

    Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by, and adhesion of human eosinophils to, HEFs and HEMCs. Eosinophil products were tested in an esophageal muscle contraction assay. Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were secreted spontaneously in mucosal biopsy specimens from patients with EoE than controls. Exposure of HEFs and HEMCs to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEFs and HEMCs to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor β1 and p38 mitogen-activated protein kinase signaling. Eosinophil binding to HEFs and HEMCs increased after incubation of mesenchymal cells with eosinophil-derived products, and decreased after blockade of transforming growth factor β1 and p38 mitogen-activated protein kinase blockade. Eosinophil products reduced

  4. A human coronavirus responsible for the common cold massively kills dendritic cells but not monocytes.

    Science.gov (United States)

    Mesel-Lemoine, Mariana; Millet, Jean; Vidalain, Pierre-Olivier; Law, Helen; Vabret, Astrid; Lorin, Valérie; Escriou, Nicolas; Albert, Matthew L; Nal, Béatrice; Tangy, Frédéric

    2012-07-01

    Human coronaviruses are associated with upper respiratory tract infections that occasionally spread to the lungs and other organs. Although airway epithelial cells represent an important target for infection, the respiratory epithelium is also composed of an elaborate network of dendritic cells (DCs) that are essential sentinels of the immune system, sensing pathogens and presenting foreign antigens to T lymphocytes. In this report, we show that in vitro infection by human coronavirus 229E (HCoV-229E) induces massive cytopathic effects in DCs, including the formation of large syncytia and cell death within only few hours. In contrast, monocytes are much more resistant to infection and cytopathic effects despite similar expression levels of CD13, the membrane receptor for HCoV-229E. While the differentiation of monocytes into DCs in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 requires 5 days, only 24 h are sufficient for these cytokines to sensitize monocytes to cell death and cytopathic effects when infected by HCoV-229E. Cell death induced by HCoV-229E is independent of TRAIL, FasL, tumor necrosis factor alpha, and caspase activity, indicating that viral replication is directly responsible for the observed cytopathic effects. The consequence of DC death at the early stage of HCoV-229E infection may have an impact on the early control of viral dissemination and on the establishment of long-lasting immune memory, since people can be reinfected multiple times by HCoV-229E.

  5. Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

    Science.gov (United States)

    Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

    2016-01-01

    Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

  6. Analysis of the Effects of the Bruton's tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcγ Receptor (FcγR) Function.

    Science.gov (United States)

    Ren, Li; Campbell, Amanda; Fang, Huiqing; Gautam, Shalini; Elavazhagan, Saranya; Fatehchand, Kavin; Mehta, Payal; Stiff, Andrew; Reader, Brenda F; Mo, Xiaokui; Byrd, John C; Carson, William E; Butchar, Jonathan P; Tridandapani, Susheela

    2016-02-05

    The irreversible Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma. Fcγ receptors (FcγR) on immune cells such as macrophages play an important role in tumor-specific antibody-mediated immune responses, but many such responses involve Btk. Here we tested the effects of ibrutinib on FcγR-mediated activities in monocytes. We found that ibrutinib did not affect monocyte FcγR-mediated phagocytosis, even at concentrations higher than those achieved physiologically, but suppressed FcγR-mediated cytokine production. We confirmed these findings in macrophages from Xid mice in which Btk signaling is defective. Because calcium flux is a major event downstream of Btk, we tested whether it was involved in phagocytosis. The results showed that blocking intracellular calcium flux decreased FcγR-mediated cytokine production but not phagocytosis. To verify this, we measured activation of the GTPase Rac, which is responsible for actin polymerization. Results showed that ibrutinib did not inhibit Rac activation, nor did the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester). We next asked whether the effect of ibrutinib on monocyte FcγR-mediated cytokine production could be rescued by IFNγ priming because NK cells produce IFNγ in response to antibody therapy. Pretreatment of monocytes with IFNγ abrogated the effects of ibrutinib on FcγR-mediated cytokine production, suggesting that IFNγ priming could overcome this Btk inhibition. Furthermore, in monocyte-natural killer cell co-cultures, ibrutinib did not inhibit FcγR-mediated cytokine production despite doing so in single cultures. These results suggest that combining ibrutinib with monoclonal antibody therapy could enhance chronic lymphocytic leukemia cell killing without affecting macrophage effector function. © 2016 by The American Society for Biochemistry

  7. Analysis of the Effects of the Bruton's tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcγ Receptor (FcγR) Function*

    Science.gov (United States)

    Ren, Li; Campbell, Amanda; Fang, Huiqing; Gautam, Shalini; Elavazhagan, Saranya; Fatehchand, Kavin; Mehta, Payal; Stiff, Andrew; Reader, Brenda F.; Mo, Xiaokui; Byrd, John C.; Carson, William E.; Butchar, Jonathan P.; Tridandapani, Susheela

    2016-01-01

    The irreversible Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma. Fcγ receptors (FcγR) on immune cells such as macrophages play an important role in tumor-specific antibody-mediated immune responses, but many such responses involve Btk. Here we tested the effects of ibrutinib on FcγR-mediated activities in monocytes. We found that ibrutinib did not affect monocyte FcγR-mediated phagocytosis, even at concentrations higher than those achieved physiologically, but suppressed FcγR-mediated cytokine production. We confirmed these findings in macrophages from Xid mice in which Btk signaling is defective. Because calcium flux is a major event downstream of Btk, we tested whether it was involved in phagocytosis. The results showed that blocking intracellular calcium flux decreased FcγR-mediated cytokine production but not phagocytosis. To verify this, we measured activation of the GTPase Rac, which is responsible for actin polymerization. Results showed that ibrutinib did not inhibit Rac activation, nor did the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester). We next asked whether the effect of ibrutinib on monocyte FcγR-mediated cytokine production could be rescued by IFNγ priming because NK cells produce IFNγ in response to antibody therapy. Pretreatment of monocytes with IFNγ abrogated the effects of ibrutinib on FcγR-mediated cytokine production, suggesting that IFNγ priming could overcome this Btk inhibition. Furthermore, in monocyte-natural killer cell co-cultures, ibrutinib did not inhibit FcγR-mediated cytokine production despite doing so in single cultures. These results suggest that combining ibrutinib with monoclonal antibody therapy could enhance chronic lymphocytic leukemia cell killing without affecting macrophage effector function. PMID:26627823

  8. Eosinophilic Otitis Media: CT and MRI Findings and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Won Jung; Lee, Jeong Hyun; Lim, Hyun Kyung; Yoon, Tae Hyun; Cho, Kyung Ja; Baek, Jung Hwan [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    Eosinophilic otitis media (EOM) is a relatively rare, intractable, middle ear disease with extremely viscous mucoid effusion containing eosinophils. EOM is associated with adult bronchial asthma and nasal allergies. Conventional treatments for otitis media with effusion (OME) or for chronic otitis media (COM), like tympanoplasty or mastoidectomy, when performed for the treatment of EOM, can induce severe complications such as deafness. Therefore, it should be differentiated from the usual type of OME or COM. To our knowledge, the clinical and imaging findings of EOM of temporal bone are not well-known to radiologists. We report here the CT and MRI findings of two EOM cases and review the clinical and histopathologic findings of this recently described disease entity.

  9. Eosinophilic Otitis Media: CT and MRI Findings and Literature Review

    International Nuclear Information System (INIS)

    Chung, Won Jung; Lee, Jeong Hyun; Lim, Hyun Kyung; Yoon, Tae Hyun; Cho, Kyung Ja; Baek, Jung Hwan

    2012-01-01

    Eosinophilic otitis media (EOM) is a relatively rare, intractable, middle ear disease with extremely viscous mucoid effusion containing eosinophils. EOM is associated with adult bronchial asthma and nasal allergies. Conventional treatments for otitis media with effusion (OME) or for chronic otitis media (COM), like tympanoplasty or mastoidectomy, when performed for the treatment of EOM, can induce severe complications such as deafness. Therefore, it should be differentiated from the usual type of OME or COM. To our knowledge, the clinical and imaging findings of EOM of temporal bone are not well-known to radiologists. We report here the CT and MRI findings of two EOM cases and review the clinical and histopathologic findings of this recently described disease entity.

  10. Investigation of CT diagnostic imaging of 'Eosinophilic chronic rhinosinusitis'

    International Nuclear Information System (INIS)

    Ogino, Nobuhiro; Matsuwaki, Yoshinori; Ojiri, Hiroya; Kanou, Asami; Fukuda, Kunihiko

    2011-01-01

    'Eosinophilic chronic rhinosinusitis (ECRS)' is a newly developed entity of chronic rhinosinusitis, which shows resistance against conventional treatment and poor prognosis. Pathologically, ECRS is manifested by high-degree of eosinophilic infiltration in the paranasal sinus mucosa. We structure the CT diagnostic criteria of ECRS and assess its availability. This diagnostic criteria consists of disease distribution (bilateral and predominant in the ethmoid sinus), existence of nasal polyp (s) and high attenuation which suggestive of allergic mucine. We retrospectively review CT of clinically diagnosed 14 ECRS cases to see if CT features of each case fit the criteria or not. The current CT diagnostic criteria of ECRS were proven to be useful to evaluate cases with clinical suspicion of ECRS. (author)

  11. Genes Associated with Food Allergy and Eosinophilic Esophagitis

    Science.gov (United States)

    2013-11-01

    esophageal fibrosis in a mouse model of eosinophilic esophagitis. J Allergy Clinical Immunology (2013), 507. Original Manuscripts Jae Youn Cho...Broide MB ChB1 1Allergy and Immunology , Department of Medicine, University of California San Diego. 2Allergy and Immunology , Department of...acetylglucosamine re- peats [1,2]. Chitin is highly expressed in insects and crustacean exoskeletons, fungal cell walls, and microfilarial nematode

  12. Evaluation of the Effectiveness of Antibiotics against Eosinophilic Pustular Folliculitis

    Directory of Open Access Journals (Sweden)

    Sachiko Ono

    2013-05-01

    Full Text Available Eosinophilic pustular folliculitis (EPF is a chronic intractable pruritic dermatosis. Although indomethacin is generally effective against EPF and considered as a first-line therapy, quite a few patients with indomethacin still suffer from the symptoms. Among other therapeutic options, some antibiotics have been reported to be effective; however, there has been no epidemiological description regarding oral antibiotics use in patients with EPF. In this study, we investigated the frequency of antibiotics use and the effectiveness in patients with EPF.

  13. Clinical lesson: eosinophilic oesophagitis, a new diagnosis to swallow

    OpenAIRE

    Lamb, C A; Kanakala, V; Stirling, R W; Attwood, S E A

    2010-01-01

    Eosinophilic oesophagitis (EoE) is a recently described condition that has gained increasing recognition over the past 5 years. Despite this, many clinicians remain unaware of EoE, often leading to diagnostic delay and therefore significant morbidity. The diagnosis of EoE should be considered in any patient with a history of intermittent or continuous dysphagia, or oesophageal food impaction. It should be strongly suspected in young patients, particularly men, presenting with dysphagia and a ...

  14. Reliability of histologic assessment in patients with eosinophilic oesophagitis.

    Science.gov (United States)

    Warners, M J; Ambarus, C A; Bredenoord, A J; Verheij, J; Lauwers, G Y; Walsh, J C; Katzka, D A; Nelson, S; van Viegen, T; Furuta, G T; Gupta, S K; Stitt, L; Zou, G; Parker, C E; Shackelton, L M; D Haens, G R; Sandborn, W J; Dellon, E S; Feagan, B G; Collins, M H; Jairath, V; Pai, R K

    2018-04-01

    The validity of the eosinophilic oesophagitis (EoE) histologic scoring system (EoEHSS) has been demonstrated, but only preliminary reliability data exist. Formally assess the reliability of the EoEHSS and additional histologic features. Four expert gastrointestinal pathologists independently reviewed slides from adult patients with EoE (N = 45) twice, in random order, using standardised training materials and scoring conventions for the EoEHSS and additional histologic features agreed upon during a modified Delphi process. Intra- and inter-rater reliability for scoring the EoEHSS, a visual analogue scale (VAS) of overall histopathologic disease severity, and additional histologic features were assessed using intra-class correlation coefficients (ICCs). Almost perfect intra-rater reliability was observed for the composite EoEHSS scores and the VAS. Inter-rater reliability was also almost perfect for the composite EoEHSS scores and substantial for the VAS. Of the EoEHSS items, eosinophilic inflammation was associated with the highest ICC estimates and consistent with almost perfect intra- and inter-rater reliability. With the exception of dyskeratotic epithelial cells and surface epithelial alteration, ICC estimates for the remaining EoEHSS items were above the benchmarks for substantial intra-rater, and moderate inter-rater reliability. Estimation of peak eosinophil count and number of lamina propria eosinophils were associated with the highest ICC estimates among the exploratory items. The composite EoEHSS and most component items are associated with substantial reliability when assessed by central pathologists. Future studies should assess responsiveness of the score to change after a therapeutic intervention to facilitate its use in clinical trials. © 2018 John Wiley & Sons Ltd.

  15. Elimination diets in the management of eosinophilic esophagitis

    Directory of Open Access Journals (Sweden)

    Wechsler JB

    2014-05-01

    Full Text Available Joshua B Wechsler, Sally Schwartz, Katie Amsden, Amir F Kagalwalla Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, IL, USA Abstract: Eosinophilic esophagitis, an increasingly recognized chronic inflammatory disorder isolated to the esophagus, is triggered by an abnormal allergic response to dietary antigens. Current treatment includes swallowed topical steroids and dietary modification, which aim to resolve symptoms and prevent long-term complications such as formation of strictures. The dietary approach has become more widely accepted because long-term steroid therapy is associated with potential risks. Dietary treatment includes elemental and elimination diets. An exclusive elemental diet, which requires replacement of all intact protein with amino acid-based formula, offers the best response of all available therapies, with remission in up to 96% of subjects proving it to be superior to all other available therapies including topical steroids. However, compliance with this approach is challenging because of poor taste and monotony. The high cost of formula and the associated psychosocial problems are additional drawbacks of this approach. Empiric and allergy test-directed elimination diets have gained popularity given that elimination of a limited number of foods is much easier and as such is more readily acceptable. There is a growing body of literature supporting this type of therapy in both children and adults. This paper reviews the evidence for all types of dietary therapy in eosinophilic esophagitis. Keywords: eosinophilic esophagitis, dietary therapy, empiric elimination, elemental, allergy test-directed

  16. Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice.

    Science.gov (United States)

    Ramanathan, Murugappan; London, Nyall R; Tharakan, Anuj; Surya, Nitya; Sussan, Thomas E; Rao, Xiaoquan; Lin, Sandra Y; Toskala, Elina; Rajagopalan, Sanjay; Biswal, Shyam

    2017-07-01

    Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 μm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 μm/m 3 , a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.

  17. Imaginal diagnosis of eosinophilic granuloma of long bones

    International Nuclear Information System (INIS)

    Cui Fa; Cui Minyi

    2006-01-01

    Objective: To analyze the clinical and imaging features of eosinophilic granuloma of long bones so as to improve diagnosis accuracy of the disease. Methods: The clinic materials and imaging findings of 24 patients with eosinophilic granuloma of long bones proved by surgery or histopathology were analyzed retrospectively. All the patients received radiography; CT scan was performed in 6 cases; and MRI was done in 4 cases. Results: Fifteen patients out of 24 were male and 9 were female, with the average age 14. 7 years old. Solitary lesion was found in 22 cases, and multiple bone destruction was noted in 2 cases. There were 14 lesions located in femur; 5 in tibia; 3 in humer; and 2 in fibula. In total 16 lesions involved diaphysis and in 8 cases the metaphysis was invaded. Bone destruction, the changes of the adjacent cortex, periosteal reaction and soft tissue mass or swelling were demonstrated in images obtained. Conclusion: The imaging features in eosinophilic granuloma of long bones are characteristic. Careful and integrative analysis of imaging findings improves diagnosis accuracy of the disease. (authors)

  18. Point-of-care blood eosinophil count in a severe asthma clinic setting.

    Science.gov (United States)

    Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

    2017-07-01

    One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma

    DEFF Research Database (Denmark)

    Duong, MyLinh; Subbarao, Padmaja; Adelroth, Ellinor

    2008-01-01

    BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double...... and sputum analysis were performed. RESULTS: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated...... eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of eosinophilic groups in the magnitude of improvement in EIB was evident after the first...

  20. Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells.

    Science.gov (United States)

    Lin, Jing-Yi; Ta, Yng-Cun; Liu, I-Lin; Chen, Hsi-Wen; Wang, Li-Fang

    2016-07-01

    Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Atypical lymphocytes in malaria mimicking dengue infection in Thailand

    Directory of Open Access Journals (Sweden)

    Polrat Wilairatana

    2010-09-01

    Full Text Available Polrat Wilairatana1, Noppadon Tangpukdee1, Sant Muangnoicharoen1, Srivicha Krudsood2, Shigeyuki Kano31Department of Clinical Tropical Medicine, 2Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 3Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, JapanAbstract: Patients with uncomplicated falciparum or vivax malaria usually present with acute febrile illness and thrombocytopenia similar to dengue infection. We retrospectively studied atypical lymphocytes (AL and atypical lymphocytosis (ALO, defined as AL > 5% of total white blood cells in 1310 uncomplicated malaria patients. In 718 falciparum malaria patients, AL and ALO on day 0 were found in 53.2% and 5.7% of the patients, respectively, with median AL on admission of 1% (range 0%–10%, whereas in 592 vivax malaria patients, AL and ALO on day 0 were found in 55.4% and 9.5% of the patients, respectively, with median AL on admission of 1% (range 0%–14%. After antimalarial treatment, AL and ALO declined in both falciparum and vivax malaria. However, AL and ALO remained in falciparum malaria on days 7, 14, and 21, whereas AL and ALO remained in vivax malaria on days 7, 14, 21, and 28. In both falciparum and vivax malaria patients, there was a positive correlation between AL and total lymphocytes, but a negative correlation between AL and highest fever on admission, white blood cells, and neutrophils, eosinophils, and platelets (P < 0.05. In conclusion, AL or ALO may be found in uncomplicated falciparum and vivax malaria mimicking dengue infection. In tropical countries where both dengue and malaria are endemic, presence of AL or ALO in any acute febrile patients with thrombocytopenia (similar to the findings in dengue malaria could not be excluded. Particularly if the patients have risk of malaria infection, confirmative microscopic examination for malaria should be carried out

  2. A simple method for human peripheral blood monocyte Isolation

    Directory of Open Access Journals (Sweden)

    Marcos C de Almeida

    2000-04-01

    Full Text Available We describe a simple method using percoll gradient for isolation of highly enriched human monocytes. High numbers of fully functional cells are obtained from whole blood or buffy coat cells. The use of simple laboratory equipment and a relatively cheap reagent makes the described method a convenient approach to obtaining human monocytes.

  3. Monocyte function is severely impaired by the fluorochrome calcein acetomethylester

    International Nuclear Information System (INIS)

    Czepluch, Frauke S.; Olieslagers, Serve J.F.; Waltenberger, Johannes

    2007-01-01

    For rapid chemotaxis quantification, cell prelabelling is often performed with the fluorochrome calcein acetomethylester (calcein AM). We investigated whether calcein AM-prelabelling is reliable for monocyte migration analysis. Human monocytes were either preexposed to calcein AM or unlabelled. Monocyte migration towards the potent chemoattractants transforming growth factor-β1 (TGF-β1) and N-formyl-Methionin-Leucin-Phenylalanin (fMLP) was assessed using a 48-well micro-chemotaxis chamber. For quantification, cells were visualized by light microscopy and counted. Surprisingly, random migration of calcein AM-prelabelled cells was significantly impaired compared to the unlabelled control. Accordingly, monocyte chemotaxis towards either TGF-β1 or fMLP dramatically declined. Adherence of calcein AM-labelled monocytes on plastic was also significantly decreased compared to control cells. As adhesion is regarded as an essential component of monocyte migration, the reduced migration observed in calcein AM-labelled monocytes might be explained by a fluorochrome-induced adhesion defect. Therefore, use of the fluorochrome calcein AM cannot be recommended for functional testing of monocytes

  4. Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jamille Souza Fernandes

    2014-01-01

    Full Text Available A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16−, intermediate (CD14++CD16+, and nonclassical (CD14+CD16++. The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-β was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

  5. Blood monocyte oxidative burst activity in acute P. falciparum malaria

    DEFF Research Database (Denmark)

    Nielsen, H; Theander, T G

    1989-01-01

    The release of superoxide anion from blood monocytes was studied in eight patients with acute primary attack P. falciparum malaria. Before treatment a significant enhancement of the oxidative burst prevailed, which contrasts with previous findings of a depressed monocyte chemotactic responsiveness...

  6. Effect of radiotherapy on lymphocyte populations in lung cancer

    International Nuclear Information System (INIS)

    Gava, A.; Coghetto, F.; Marazzato, G.; Fantin, P.L.; Patrese, P.; Moro, L.; De Angeli, S.

    1988-01-01

    The authors report on the results of the immune monitoring of a study population of 31 patients with lung cancer who were treated with radiotherapy. Asynthetic thymic pentapeptide, Thymopentin, was employed-whose effect was evaluated on the immunological parameters analyzed. After radiotherapy, a considerable and homogeneous decrement was observed in several lymphocytic subset (less sensible in activated T-cells), together with a progressive decrement in the helper/suppressor ratio, in the long run. Monocytes and null cells showed more radioresistance. Thymopentin had no influence on the tested immunological parameters up tp 6 months after radiotherapy; later on, a slightly more balanced helper/suppressor ratio could be noticed in the surviving patients who had benn treated with Thymopentin

  7. [Effects of radiotherapy on lymphocyte populations in lung cancer].

    Science.gov (United States)

    Gava, A; Moro, L; De Angeli, S; Coghetto, F; Marazzato, G; Fantin, P; Patrese, P

    1988-11-01

    The authors report on the results of the immune monitoring of a study population of 31 patients with lung cancer who were treated with radiotherapy. A synthetic thymic pentapeptide, thymopentin, was employed whose effect was evaluated on the immunological parameters analyzed. After radiotherapy, a considerable and homogeneous decrement was observed in several lymphocytic subsets (less sensible in activated T-cells), together with a progressive decrement in the helper/suppressor ratio, in the long run. Monocytes and null cells showed more radioresistance. Thymopentin had no influence on the tested immunological parameters up to 6 months after radiotherapy; later on, a slightly more balanced helper/suppressor ratio could be noticed in the surviving patients who had been treated with thymopentin.

  8. Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to uropathogenic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Benjamin L Duell

    Full Text Available Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10 in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.

  9. Studies on the production of endogenous pyrogen by rabbit monocytes: the role of calcium and cyclic nucleotides.

    Science.gov (United States)

    Sigal, S L; Duff, G W; Atkins, E

    1985-01-01

    Rabbit monocytes stimulated with endotoxin produced endogenous pyrogen, even under conditions of high or low extracellular calcium concentrations. Maximal production occurred when the concentration was in the near-physiological range. Prolonged incubation of cells with a calcium chelator prevented subsequent activation with endotoxin, an effect which was rapidly reversible by re-addition of calcium but not other cations. Addition of small amounts of lanthanum, which acts as a calcium channel blocker, prevented the restoration of pyrogen production, indicating that entry of the added calcium into the monocyte was required. Incorporation of a calcium ionophore into the cell membrane did not stimulate pyrogen production, and no measurable influx or efflux of calcium occurred during stimulation with endotoxin. These observations suggest that a slowly exchangeable calcium pool is necessary for the production of endogenous pyrogen, but that a rise in intracellular calcium is not by itself a necessary or sufficient stimulus. This stands in contrast to other biological systems in which Ca2+ directly couples stimulus and hormone secretion. Incubation of cells with agents shown to increase cyclic 3',5' AMP or cyclic 3',5' GMP levels in monocytes similarly did not stimulate pyrogen production or modulate its production by endotoxin stimulation. Thus, cyclic nucleotides also did not play a detectable role as intracellular messengers in this system. Future work is required to define more clearly the mechanism for the production of endogenous pyrogen, given its marked effects on the immune system through lymphocyte activation and temperature regulation.

  10. Intestinal perforation in a two-year-old child with eosinophilic gastroenteritis

    DEFF Research Database (Denmark)

    Agertoft, A; Husby, S; Høst, A

    1991-01-01

    A two-year-old boy underwent a laparatomy for an intestinal perforation due to eosinophilic gastroenteritis. He had marked peripheral blood eosinophilia and a small duodenal biopsy showed heavy eosinophilic infiltration in the mucosa. After 1 1/2 year on a restricted diet, a control duodenal biopsy...... showed only slight eosinophilia. Perforation of the small intestine is a rare but serious complication in eosinophilic gastroenteritis....

  11. Extracellular microvesicle production by human eosinophils activated by “inflammatory” stimuli

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    Praveen Akuthota

    2016-10-01

    Full Text Available A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs, very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1 and tumor necrosis factor alpha (TNF-α. EV production was investigated by nanoscale flow cytometry, conventional transmission electron microscopy (TEM and pre-embedding immunonanogold EM. The tetraspanins CD63 and CD9 were used as EV biomarkers for both flow cytometry and ultrastructural immunolabeling. Nanoscale flow cytometry showed that human eosinophils produce EVs in culture and that a population of EVs expressed detectable CD9, while CD63 was not consistently detected. When eosinophils were stimulated immediately after isolation and analyzed by TEM, EVs were clearly identified as microvesicles (MVsoutwardly budding off the plasma membrane. Both CCL11 and TNF-α induced significant increases of MVs compared to unstimulated cells.TNF-α induced amplified release of MVs more than CCL11. Eosinophil MV diameters varied from 20-1000 nm. Immunonanogold EM revealed clear immunolabeling for CD63 and CD9 on eosinophil MVs, although not all MVs were labeled. Altogether, we identified, for the first time, that human eosinophils secrete MVs and that this production increases in response to inflammatory stimuli. This is important to understand the complex secretory activities of eosinophils underlying immune

  12. Phenotypic heterogeneity of peripheral monocytes in healthy dogs.

    Science.gov (United States)

    Gibbons, Natalie; Goulart, Michelle R; Chang, Yu-Mei; Efstathiou, Konstantinos; Purcell, Robert; Wu, Ying; Peters, Laureen M; Turmaine, Mark; Szladovits, Balazs; Garden, Oliver A

    2017-08-01

    Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By flow cytometry, we demonstrated that canine monocytes can be subdivided into three separate populations: CD14 pos MHC II neg , CD14 pos MHC II pos and CD14 neg MHC II pos . Both light and transmission electron microscopy confirmed the monocytic identity of all three populations. The CD14 pos MHC II neg population could be distinguished on an ultrastructural level by their smaller size, the presence of more numerous, larger granules, and more pseudopodia than both of the other populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Improvement in the Function of rat Peripheral Blood Monocytes Following Oral Administration of Curcumin

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    H Zirak Marangalu

    2017-06-01

    Conclusions: Collectively, it seems that curcumin is a natural source to intervene the monocytes functions especially in autoimmune diseases so that monocytes hyperactivity causes immunopathological conditions.

  14. Lymphocyte signaling: beyond knockouts.

    Science.gov (United States)

    Saveliev, Alexander; Tybulewicz, Victor L J

    2009-04-01

    The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Although this gene 'knockout' approach is often informative, in many cases, the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to 'knock in' subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully based on structural and biophysical data.

  15. MRI of lymphocytic hypophysitis

    International Nuclear Information System (INIS)

    Feng Feng; Li Mingli; Li Xiaozhen; Meng Chunling; Jin zhengyu

    2005-01-01

    Objective: To describe the MR findings in patients with lymphocytic hypophysitis (LyH), and to discuss MR diagnostic value and limit in this disease entity and its differentiation with pituitary adenoma. Methods: Five pathologically proven cases of LyH were recruited in this study. The main complaints of the patients were polydipsia, polyuria, and headache. The preoperative MR images and clinical manifestations were analyzed retrospectively. Results: MR findings of the 5 patients with LyH included enlargement of pituitary gland, stalk thickening, disappearance of high signal of neurohypophysis on T 1 WI, and marked Gadolinium enhancement of the lesions. Homogeneous enhancement was found in 2 cases, while heterogeneous enhancement was in 3 cases. Involvement of the cavernous sinus and dura mater on dorsum sella and clivus were found in 2 patients. Conclusion: The diagnosis of LyH should be suggested when the enlarged pituitary gland is associated with central diabetes insipidus, and with/without dysfunction of adenohypophysis. (authors)

  16. Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune Fallgaard; Lange, Peter

    2017-01-01

    BACKGROUND: Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated...... with the risk of asthma exacerbations among individuals with asthma from the general population. METHODS: From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during...... with blood eosinophil counts >0.29 × 10(9)/L (highest tertile) vs individuals with blood eosinophil counts

  17. In vivo activation of equine eosinophils and neutrophils by experimental Strongylus vulgaris infections.

    Science.gov (United States)

    Dennis, V A; Klei, T R; Chapman, M R; Jeffers, G W

    1988-12-01

    Eosinophils and neutrophils from ponies with Strongylus vulgaris-induced eosinophilia (eosinophilic ponies; activated eosinophils and neutrophils) were assayed in vitro for chemotactic and chemokinetic responses to zymosan-activated serum (ZAS) using the filter system in Boyden chambers, for Fc and complement (C) receptors using the EA and EAC-rosette assays, respectively, and for phagocytic and bactericidal activities using opsonized Escherichia coli and the acridine orange method. The responses of activated eosinophils and neutrophils in the above assays were compared with those of eosinophils and neutrophils from S. vulgaris-naive ponies without eosinophilia (noneosinophilic ponies; nonactivated eosinophils and neutrophils). Differences in cell density following centrifugation in a continuous Percoll gradient were used to further characterize the heterogeneity of activated eosinophils and neutrophils. Activated and nonactivated eosinophils demonstrated similar chemotactic responses to ZAS while activated and nonactivated neutrophils demonstrated similar chemokinetic responses to ZAS. A higher percentage of activated eosinophils and neutrophils expressed Fc and C receptors compared with nonactivated cells (P less than 0.05). Generally, higher percentages of eosinophils and neutrophils expressed C than Fc receptors. However, the percentage of neutrophils with both receptors was higher than that of eosinophils. Phagocytosis and killing of E. coli by either type of eosinophil were not consistently observed. Both activated and nonactivated neutrophils phagocytized E. coli and significant differences between the two cell types were not observed. The bacterial activity, however, of activated neutrophils was significantly greater than that obtained using nonactivated neutrophils (P less than 0.05). Activated eosinophils and neutrophils were both separated into two distinct fractions based on differences in cell densities. A higher percentage of band 2 eosinophils

  18. Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tashkin DP

    2018-01-01

    Full Text Available Donald P Tashkin,1 Michael E Wechsler2 1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. Keywords: lung disease, pulmonary diseases, corticosteroids, asthma, pneumonia

  19. Bronchoalveolar lavage and technetium-99m glucoheptonate imaging in chronic eosinophilic pneumonia

    International Nuclear Information System (INIS)

    Lieske, T.R.; Sunderrajan, E.V.; Passamonte, P.M.

    1984-01-01

    A patient with chronic eosinophilic pneumonia was evaluated using bronchoalveolar lavage, technetium-99m glucoheptonate, and transbronchial lung biopsy. Bronchoalveolar lavage revealed 43 percent eosinophils and correlated well with results of transbronchial lung biopsy. Technetium-99m glucoheptonate lung imaging demonstrated intense parenchymal uptake. After eight weeks of corticosteroid therapy, the bronchoalveolar lavage eosinophil population and the technetium-99m glucoheptonate uptake had returned to normal. We suggest that bronchoalveolar lavage, with transbronchial lung biopsy, is a less invasive way than open lung biopsy to diagnose chronic eosinophilic pneumonia. The mechanism of uptake of technetium-99m glucoheptonate in this disorder remains to be defined

  20. Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells' syndrome to Churg-Strauss syndrome?

    Science.gov (United States)

    Ratzinger, Gudrun; Zankl, Julia; Eisendle, Klaus; Zelger, Bernhard

    2014-01-01

    Wells' syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates, vasculitis and flame figures. To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process. Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells' syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells' syndrome at least once in the course of their disease. 4 patients were finally diagnosed with Wells' syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells' syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients. Histologically, we find vasculitic features in typical presentations of Wells' syndrome. Clinically, we find typical features of Wells' syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells' syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells' syndrome and Churg Strauss syndrome.

  1. EOSINOPHILIC INFLAMMATORY DISEASES OF THE GASTROINTESTINAL TRACT AND FOOD ALLERGY AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    P.V. Shumilov

    2007-01-01

    Full Text Available Within the structure of the inflammatory diseases of the gastrointestinal tract among children, one may single out a specific group of the chronic pathology of the digestive apparatus — eosinophilic diseases of the gastrointestinal tract and gastroenterological manifestations of the food allergy. The food allergy is characterized by the pathologic immune reactivity among commonly genetically predisposed people. Depending on the peculiarities of the immune reactivity of a sick person and the nature of the allergen, the allergic reaction may evolve with primary involvement of the different mechanisms or th2 IgE-mediated, or Th1 non-igecmediated. Clinical picture of the food allergy is the manifestation of the immunoinflammatory process caused by the interaction of the food antigens with the structures of the lymphoid tissues associated with the mucous membranes of this or that target organ. The morphological basis of the clinical picture is mostly immune inflammation with primarily eosinophilic tissue infiltration. The eosinophilic lesions of the gastrointestinal tract include eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic enteritis, eosinophilic colitis, eosinophilic proctitis and other states. During the food allergy each of the clinical forms of the gastrointestinal tract lesion has its own peculiarities with regards to the primary development mechanism, age of manifestation, character of the run and behaviour tactics.Key words: eosinophilic inflammation, esophagitis, gastroenteritis, colitis, food allergy.

  2. Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

    Science.gov (United States)

    Kawabori, Masashi; Kurihara, Chitaru; Miller, Yair; Heck, Kent A; Bogaev, Roberta C; Civitello, Andrew B; Cohn, William E; Frazier, O H; Morgan, Jeffrey A

    2017-09-01

    Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

  3. Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis

    Science.gov (United States)

    Griseri, Thibault; Arnold, Isabelle C.; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S.; Crocker, Paul R.; Powrie, Fiona

    2015-01-01

    Summary The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. PMID:26200014

  4. Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

    Science.gov (United States)

    Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

    2016-06-01

    Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders.

    Science.gov (United States)

    Barnig, Cindy; Alsaleh, Ghada; Jung, Nicolas; Dembélé, Doulaye; Paul, Nicodème; Poirot, Anh; Uring-Lambert, Béatrice; Georgel, Philippe; de Blay, Fréderic; Bahram, Seiamak

    2015-01-01

    Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology.

  6. Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice

    International Nuclear Information System (INIS)

    Runge, V.M.; Rand, T.H.; Clanton, J.A.; Jones, J.P.; Colley, D.G.; Partain, C.L.; James, A.E. Jr.

    1983-01-01

    Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease

  7. Exosome secretion by eosinophils: A possible role in asthma pathogenesis.

    Science.gov (United States)

    Mazzeo, Carla; Cañas, José Antonio; Zafra, Maria Paz; Rojas Marco, Ainara; Fernández-Nieto, Mar; Sanz, Veronica; Mittelbrunn, María; Izquierdo, Manuel; Baixaulli, Francesc; Sastre, Joaquín; Del Pozo, Victoria

    2015-06-01

    Eosinophils secrete several granules that are involved in the propagation of inflammatory responses in patients with pathologies such as asthma. We hypothesized that some of these granules are exosomes, which, when transferred to the recipient cells, could modulate asthma progression. Eosinophils were purified from peripheral blood and cultured with or without IFN-γ or eotaxin. Multivesicular bodies (MVBs) in eosinophils were studied by using fluorescence microscopy, transmission electron microscopy (TEM), and flow cytometry. Exosome secretion was measured and exosome characterization was performed with TEM, Western blotting, and NanoSight analysis. Generation of MVBs in eosinophils was confirmed by using fluorescence microscopy and flow cytometry and corroborated by means of TEM. Having established that eosinophils contain MVBs, our aim was to demonstrate that eosinophils secrete exosomes. To do this, we purified exosomes from culture medium of eosinophils and characterized them. Using Western blot analysis, we demonstrated that eosinophils secreted exosomes and that the discharge of exosomes to extracellular media increases after IFN-γ stimulation. We measured exosome size and quantified exosome production from healthy and asthmatic subjects using nanotracking analysis. We found that exosome production was augmented in asthmatic patients. Our findings are the first to demonstrate that eosinophils contain functional MVBs and secrete exosomes and that their secretion is increased in asthmatic patients. Thus exosomes might play an important role in the progression of asthma and eventually be considered a biomarker. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis.

    Science.gov (United States)

    Braga, Fernanda Gambogi; Ruas, Luciana Pereira; Pereira, Ricardo Mendes; Lima, Xinaida Taligare; Antunes, Edson; Mamoni, Ronei Luciano; Blotta, Maria Heloisa Souza Lima

    2017-05-01

    Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower population of CD80+ cells. We also evaluated the fungicidal capacity of eosinophils in vitro. Our results revealed that eosinophils from PCM patients and controls exhibit similar ability to kill P. brasiliensis yeast cells, although eosinophils of patients were less responsive to IL-5 stimulation than controls. In conclusion, we suggest that eosinophils might play a role in the host response to fungi and in the pathophysiology of PCM by inducing an intense and systemic inflammatory response in the initial phase of the infection.

  9. Chronic eosinophilic pneumonia presenting with ipsilateral pleural effusion: a case report.

    Science.gov (United States)

    Sriratanaviriyakul, Narin; La, Hanh H; Albertson, Timothy E

    2016-08-12

    Chronic eosinophilic pneumonia is a rare idiopathic interstitial lung disease. The nearly pathognomonic radiographic finding is the peripheral distribution of alveolar opacities. Pleural effusions are rarely seen. We report a case of chronic eosinophilic pneumonia with transudative eosinophilic pleural effusion. A 57-year-old Hispanic woman, a nonsmoker with a history of controlled asthma, presented to the hospital with unresolving pneumonia despite three rounds of antibiotics over a 2-month period. She was later diagnosed with chronic eosinophilic pneumonia based on the presence of peripheral blood eosinophilia, the peripheral distribution of alveolar infiltrates on chest radiograph, and a lung parenchymal biopsy with infiltrates of eosinophils. Upon presentation, our patient had a right-sided moderate-sized pleural effusion. The pleural fluid profile was consistent with a transudative effusion with eosinophil predominance. Our patient responded promptly to oral corticosteroid treatment in a few days. The pulmonary infiltrates and pleural effusion subsided on a 1-month follow-up chest radiograph after starting corticosteroid treatment. We report the first case of chronic eosinophilic pneumonia presenting with pneumonia with ipsilateral transudative eosinophilic pleural effusion. Like other cases of chronic eosinophilic pneumonia, early recognition and diagnosis is essential and prompt treatment with corticosteroids is the mainstay of therapy. Pleural effusion resolved without the further need for therapeutic thoracentesis.

  10. Association of Canine Osteosarcoma and Monocyte Phenotype and Chemotactic Function.

    Science.gov (United States)

    Tuohy, J L; Lascelles, B D X; Griffith, E H; Fogle, J E

    2016-07-01

    Monocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA. That OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses. Eighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controls Clinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs. Cell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018). Dogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA. Copyright © 2016 The Authors. Journal of

  11. Radiosensitivity of lymphocytes in vitro

    International Nuclear Information System (INIS)

    Albrecht, S.

    1979-01-01

    The radiation-induced impairment of human T-lymphocytes was studied after in vitro exposure to 25.8 - 825.6 mC/kg (100 - 3200 R) of 60 Co γ-radiation by ascertaining the change in lymphocyte response to phytohaemagglutin stimulation. Following methods were used: (1) measurement of 3 H-thymidine uptake, (2) E-rosette test, and (3) morphological examination of transformed T-cells. The results revealed a dose-dependent decline in T-cell number which was still somewhat more marked with lymphocytes purified over Ficoll-Isopaque prior to irradiation. (author)

  12. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

  13. Review of idiopathic eosinophilic meningitis in dogs and cats, with a detailed description of two recent cases in dogs : review and clinical communication

    Directory of Open Access Journals (Sweden)

    J.H. Williams

    2008-05-01

    Full Text Available Eosinophilic meningoencephalitis (EME has been described in various species of animals and in humans. In dogs it has been associated with protozoal infections, cuterebral myiasis and various other aetiologies. Ten cases of idiopathic eosinophilic meningoencephalitis have been reported in dogs and one in a cat where the origin was uncertain or unknown. The dogs were all males, of various breeds but with a predominance of Golden Retrievers and Rottweilers; they generally had a young age of onset. Two cases with no apparent underlying aetiology were diagnosed on post mortem examination. The 18-month-old, male Boerboel presented with sudden onset of cerebellar ataxia, as well as various asymmetrical cranial nerve deficits of 2 weeks' duration and without progression. Haematology revealed a peripheral eosinophilia. Necropsy showed extreme generalised congestion especially of the meninges and blood smear and histological sections of various tissues showed intravascular erythrocyte fragmentation with the formation of microcytes. Histopathology revealed severe diffuse cerebrocortical subarachnoidal meningitis and submeningeal encephalitis, the exudate containing variable numbers of eosinophils together with neutrophils and mononuclear cells. There was also deeper white matter and hippocampal multifocal perivascular mononuclear encephalitis and multifocal periventricular malacia, gliosis and phagocytosis of white matter. The cerebellum, brain stem and spinal cord showed only mild multifocal oedema or scattered occasional axon and myelin degeneration respectively, with no inflammation. Immunohistochemical staining of central nervous tissue for Toxoplasma gondii failed to show any antigen in the central nervous tissue. Ultrastructure of a single submeningeal suspected parasitic cyst showed it to be chromatin clumping within a neuron nucleus indicating karyorrhexis. Gram stain provided no evidence of an aetiological agent. The 3-year-old Beagle bitch had a

  14. Monocyte transferrin-iron uptake in hereditary hemochromatosis

    International Nuclear Information System (INIS)

    Sizemore, D.J.; Bassett, M.L.

    1984-01-01

    Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells

  15. Distinct functional programming of human fetal and adult monocytes.

    Science.gov (United States)

    Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

    2014-03-20

    Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

  16. Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

    Science.gov (United States)

    Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

    2015-08-01

    Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

  17. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... of the lymph system . Having relatives who are Russian Jews or Eastern European Jews. Signs and symptoms ... information about clinical trials is also available. To Learn More About Chronic Lymphocytic Leukemia For more information ...

  18. Peripheral blood eosinophil counts and risk of colorectal cancer mortality in a large general population-based cohort study

    NARCIS (Netherlands)

    Taghizadeh, N.; Vonk, J.M.; Boezen, H.M.

    2011-01-01

    1583 Background: Few epidemiological studies have investigated the association between blood eosinophil counts and colorectal cancer incidence. The current prospective cohort study aims to investigate the association between peripheral blood eosinophils and colorectal cancer mortality risk. METHODS:

  19. Eosinophilic cellulitis (Wells’ syndrome) caused by a temporary henna tattoo

    Science.gov (United States)

    Celegen, Mehmet; Karkıner, Canan Sule Unsal; Günay, Ilker; Diniz, Güllden; Can, Demet

    2014-01-01

    Eosinophilic cellulitis (Wells’ syndrome) is an uncommon condition of unknown etiology. Wells’ syndrome is usually seen in adulthood but very rare in childhood. Although pathogenesis of the disease is not very clear, it is a hypersensitivity reaction developing against a variety of exogenous and endogenous antigenic stimuli. Paraphenylenediamine is a strong allergen frequently used as a temporary henna tattoo, which makes the color darker. Here, a 9-year-old male patient with Wells’ syndrome is presented, which developed following a temporary henna tattoo and shown by the patch test sensitivity to paraphenylenediamine. PMID:25395929

  20. Eosinophilic Granulomatosis with Polyangiitis and Diffuse Gastrointestinal Involvement

    Directory of Open Access Journals (Sweden)

    Diana L. Franco

    2014-10-01

    Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA, formerly named Churg-Strauss syndrome, is a rare systemic small- and medium-sized-vessel vasculitis, characterized by the presence of severe asthma as well as blood and tissue eosinophilia. Gastrointestinal (GI symptoms, like diarrhea and abdominal pain, are common; however, there are few reports of histologic evidence of GI involvement. We report the case of a patient on treatment for EGPA who presented with recurrent small bowel obstruction and choledocholithiasis. Biopsies of the esophagus, small bowel and common bile duct showed diffuse eosinophilia, with clear EGPA in the GI tract. Improved awareness of GI EGPA may allow for timely management of this disorder.

  1. Generalized morphea/eosinophilic fasciitis overlap after epoxy exposure

    Directory of Open Access Journals (Sweden)

    Warren H. Chan, MS

    2018-03-01

    Full Text Available Generalized morphea is associated with epoxy resin vapors and is characterized by the development of lesions shortly after exposure. Morphea presenting along with eosinophilic fasciitis (EF, or morphea/EF overlap, is rare and an indicator of poor prognosis and resistance to treatment. Here we present a case of generalized morphea/EF overlap linked to epoxy exposure. Our patient received multiple therapies—ultraviolet A1 phototherapy, prednisone, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab—none of which led to a significant response. The refractory nature of this disease warrants vigilance in its association with epoxy exposure.

  2. The effects of Strongylus vulgaris parasitism on eosinophil distribution and accumulation in equine large intestinal mucosa.

    Science.gov (United States)

    Rötting, A K; Freeman, D E; Constable, P D; Moore, R M; Eurell, J C; Wallig, M A; Hubert, J D

    2008-06-01

    Eosinophilic granulocytes have been associated with parasite or immune-mediated diseases, but their functions in other disease processes remain unclear. Cause and timing of eosinophil migration into the equine gastrointestinal mucosa are also unknown. To determine the effects of intestinal parasitism on eosinophils in equine large intestinal mucosa. Large intestinal mucosal samples were collected from horses and ponies (n = 16) from the general veterinary hospital population, ponies (n = 3) raised in a parasite-free environment, ponies experimentally infected with 500 infective Strongylus vulgaris larvae and treated with a proprietary anthelmintic drug (n = 14), and a similar group of ponies (n = 7) that received no anthelmintic treatment. Total eosinophil counts and eosinophil distribution in the mucosa were determined by histological examination. A mixed model analysis was performed and appropriate Bonferroni adjusted P values used for each family of comparisons. Pvulgaris and those raised in a parasite-free environment. Experimental infection with S. vulgaris, with or without subsequent anthelmintic treatment, did not change eosinophil counts, and counts were similar to those for horses from the general population. Migration of eosinophils to the equine large intestinal mucosa appears to be independent of exposure to parasites. Large intestinal mucosal eosinophils may have more functions in addition to their role in defence against parasites.

  3. Pyloric obstruction due to massive eosinophilic infiltration in a young adult dog.

    Science.gov (United States)

    Konstantinidis, Alexandros O; Mylonakis, Mathios E; Psalla, Dimitra; Soubasis, Nectarios; Papadimitriou, Dimitrios; Rallis, Timoleon S

    2017-11-01

    A 16-month-old dog was presented with chronic vomiting, anorexia, progressive weight loss, and melena. Exploratory laparotomy revealed a massive pyloric eosinophilic infiltration leading to pyloric obstruction that was treated successfully with pylorectomy. This is a novel clinical presentation of eosinophilic gastritis and highlights the need to consider it as a differential diagnosis for pyloric obstruction.

  4. Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

    Directory of Open Access Journals (Sweden)

    Alves Alessandra C

    1997-01-01

    Full Text Available In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF and leukotriene B4 (LTB4 in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

  5. Eosinophilic meningitis caused by infection of Angiostrongylus cantonensis in a traveler

    Institute of Scientific and Technical Information of China (English)

    GUAN Hongzhi; HOI Chupeng; CUI Liying; CHEN Lin

    2013-01-01

    A 55 - year - old female traveler returning from South China with acute onset of meningitis, presenting with eosinophilic pleocytosis in the cerebrospinal fluid was reported. The etiological diagnosis of angiostrongyliasis was confirmed by detection of specific serum antibody against Angiostrongylus cantonensis. Angiostrongyliasis should be considered as a major differential diagnosis for eosinophilic meningitis in the travelers to endemic regions.

  6. Regulation of Spontaneous Eosinophil Apoptosis—A Neglected Area of Importance

    Directory of Open Access Journals (Sweden)

    Pinja Ilmarinen

    2014-01-01

    Full Text Available Asthma is characterized by the accumulation of eosinophils in the airways in most phenotypes. Eosinophils are inflammatory cells that require an external survival-prolonging stimulus such as granulocyte macrophage-colony-stimulating factor (GM-CSF, interleukin (IL-5, or IL-3 for survival. In their absence, eosinophils are programmed to die by spontaneous apoptosis in a few days. Eosinophil apoptosis can be accelerated by Fas ligation or by pharmacological agents such as glucocorticoids. Evidence exists for the relevance of these survival-prolonging and pro-apoptotic agents in the regulation of eosinophilic inflammation in inflamed airways. Much less is known about the physiological significance and mechanisms of spontaneous eosinophil apoptosis even though it forms the basis of regulation of eosinophil longevity by pathophysiological factors and pharmacological agents. This review concentrates on discussing the mechanisms of spontaneous eosinophil apoptosis compared to those of glucocorticoid- and Fas-induced apoptosis. We aim to answer the question whether the external apoptotic stimuli only augment the ongoing pathway of spontaneous apoptosis or truly activate a specific pathway.

  7. A case of eosinophilic granuloma of the calvarium and the diagnostic value of the bone scintigraphy

    International Nuclear Information System (INIS)

    Sugiyama, Hirotaka; Nakashima, Yasutaka; Takahashi, Shozo; Oyama, Teruo; Nishimura, Kenichi.

    1981-01-01

    An operative case of eosinophilic granuloma in a 2 year and 3 month old boy was presented. The authors found that bone scintigraphy using sup(99m)Tc-diphosphonate is valuable in determining the spread of eosinophilic granulomatous lesion in the skull. We recommend this procedure before and after operation on this disease. (author)

  8. Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

    Science.gov (United States)

    Huang, Lu; Beiting, Daniel P; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Lee, Nancy A; Lee, James J; Appleton, Judith A

    2015-12-01

    It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.

  9. Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

    Science.gov (United States)

    Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

    2015-01-01

    Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

  10. Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome.

    Science.gov (United States)

    Wada, Taizo; Matsuda, Yusuke; Toma, Tomoko; Koizumi, Eiko; Okamoto, Hiroyuki; Yachie, Akihiro

    2016-01-01

    Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES. © 2016 S. Karger AG, Basel.

  11. An ultrastructural study of the interaction of human eosinophils with respiratory syncytial virus

    NARCIS (Netherlands)

    Kimpen, JLL; Garofalo, R; Welliver, RC; Fujihara, K; Ogra, PL

    It was shown previously that eosinophils are activated in vivo and in vitro by respiratory syncytial virus (RSV) (Garofalo et al., J Pediatr 1992: 120: 28-32; Kimpen et al., Pediatr Res 1992: 32: 160-4). For study of the interaction of eosinophils and RSV on the ultrastructural level, normodense

  12. Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia

    Science.gov (United States)

    Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a beta2 integrin expressed on human monocytes and a subset of mouse monocytes, has been shown to play a distinct role in human monocyte adhesion on endothelial c...

  13. CD14CD16 Monocyte Subset Levels in Heart Failure Patients

    Directory of Open Access Journals (Sweden)

    Chiara Barisione

    2010-01-01

    Full Text Available Our aim was to define the distribution of monocyte subsets in a cohort of congestive heart failure (CHF patients, to verify whether increased severity of CHF is linked to the expansion of specific monocyte subsets, and finally to investigate the relationship between monocyte subset relative frequencies, laboratory parameters of inflammation, and monocyte ACE expression.

  14. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

    DEFF Research Database (Denmark)

    Withers, Sarah B.; Forman, Ruth; Meza-Perez, Selene

    2017-01-01

    Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils...... in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability...... of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source...

  15. High resolution autoradiographic studies of RNA, protein and DNA synthesis during human eosinophil granulocytopoiesis

    International Nuclear Information System (INIS)

    Wickramasinghe, S.N.; Hughes, M.

    1978-01-01

    Human bone marrow cells which had been incubated with [ 3 H] uridine or [ 3 H]leucine for 1 h were studied using the technique of electron microscope-autoradiography. The autoradiographs revealed the presence of newly-synthesized RNA and protein molecules within or on a proportion of (1) the primary and secondary granules in all classes of eosinophil precursors and (2) the secondary granules in eosinophil granulocytes. It is suggested that the granule-associated RNA molecules may be concerned with the synthesis of at least some of the new protein molecules which were incorporated into the limiting membrane or substance of eosinophil granules long after the immature primary granule stage. Studies of eosinophil precursors which had been incubated with [ 3 H]thymidine for 1 h showed that the eosinophil granules did not label with this DNA precursor. (author)

  16. Isolation of Eosinophils from the Lamina Propria of the Murine Small Intestine.

    Science.gov (United States)

    Berek, Claudia; Beller, Alexander; Chu, Van Trung

    2016-01-01

    Only recently has it become apparent that eosinophils play a crucial role in mucosal immune homeostasis. Although eosinophils are the main cellular component of the lamina propria of the gastrointestinal tract, they have often been overlooked because they express numerous markers, which are normally used to characterize macrophages and/or dendritic cells. To study their function in mucosal immunity, it is important to isolate them with high purity and viability. Here, we describe a protocol to purify eosinophils from the lamina propria of the murine small intestine. The method involves preparation of the small intestine, removal of epithelial cells and digestion of the lamina propria to release eosinophils. A protocol to sort eosinophils is included.

  17. Airway eosinophils accumulate in the mediastinal lymph nodes but lack antigen-presenting potential for naive T cells

    NARCIS (Netherlands)

    van Rijt, Leonie S.; Vos, Nanda; Hijdra, Daniëlle; de Vries, Victor C.; Hoogsteden, Henk C.; Lambrecht, Bart N.

    2003-01-01

    Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed

  18. Changes in CD11b and L-selectin expression on eosinophils are mediated by human lung fibroblasts in vitro

    NARCIS (Netherlands)

    Spoelstra, FM; Hovenga, H; Noordhoek, JA; Postma, DS; Kauffman, HF

    Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronchoalveolar fluid show an activated phenotype, e.g., increased CD11b and decreased L-selectin expression. We investigated whether lung fibroblasts are able to activate eosinophils in vitro, and if so,

  19. MHC Class II and CD9 in Human Eosinophils Localize to Detergent-Resistant Membrane Microdomains

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C. N.; Spencer, Lisa A.

    2012-01-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor–stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR–containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4+ T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils. PMID:21885678

  20. The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review.

    Science.gov (United States)

    Eng, Stephanie S; DeFelice, Magee L

    2016-04-01

    The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposures as well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review.

  1. MHC Class II and CD9 in human eosinophils localize to detergent-resistant membrane microdomains.

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C N; Spencer, Lisa A; Weller, Peter F

    2012-02-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor-stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils.

  2. Vasoactive intestinal peptide (VIP) binds to guinea pig peritoneal eosinophils: A single class of binding sites with low affinity and high capacity

    International Nuclear Information System (INIS)

    Sakakibara, H.; Shima, K.; Takamatsu, J.; Said, S.I.

    1990-01-01

    VIP binds to specific receptors on lymphocytes and mononuclear cells and exhibits antiinflammatory properties. Eosinophils (Eos) contribute to inflammatory reactions but the regulation of Eos function is incompletely understood. The authors examined the binding of monoradioiodinated VIP, [Tyr( 125 I) 10 ] VIP ( 125 I-VIP), to Eos in guinea pigs. The interaction of 125 i-VIP with Eos was rapid, reversible, saturable and linearly dependent on the number of cells. At equilibrium the binding was competitively inhibited by native peptide or by the related peptide helodermin. Scatchard analysis suggested the presence of a single class of VIP binding sites with a low affinity and a high capacity. In the presence of isobutyl-methylxanthine, VIP, PHI or helodermin did not stimulate cyclic AMP accumulation in intact Eos, while PGE 2 or 1-isoproterenol did. VIP also did not inhibit superoxide anion generation from Eos stimulated by phorbol myristate acetate. The authors conclude that: (1) VIP binds to low-affinity, specific sites on guinea pig peritoneal eosinophils; (2) this binding is not coupled to stimulation of adenylate cyclase; and (3) the possible function of these binding sites is at present unknown

  3. Immunological studies in acquired immunodeficiency syndrome. Functional studies of lymphocyte subpopulations

    DEFF Research Database (Denmark)

    Hofmann, B; Ødum, Niels; Platz, P

    1985-01-01

    The lymphocyte transformation response in vitro to mitogens (phytohaemagglutinin, concanavalin A, and pokeweed mitogen) and antigens (purified protein derivative and tetanus) was studied in three patients with acquired immunodeficiency syndrome (AIDS), three patients with pre-AIDS, and six healthy...... controls before and after depletion of T4- or T8-positive cells. In controls, T8-depleted lymphocytes responded as well as peripheral blood mononuclear cells (PBMC) when monocytes were added, whereas T4-depleted cells gave about 50% of this response to mitogens and no response at all to antigens....... No evidence of suppression was seen when various mixtures of T4- and T8-depleted cells were made. In particular, there was a virtually linear relationship between the percentage of T8-depleted cells and the response to antigens. The PBMC of all AIDS and pre-AIDS patients had very low or absent responses...

  4. Ultrastructural findings in Hashimoto's thyroiditis and focal lymphocytic thyroiditis with reference to giant cell formation.

    Science.gov (United States)

    Knecht, H; Hedinger, C E

    1982-09-01

    Ultrastructural findings in two cases of Hashimoto's disease and two cases of focal lymphocytic thyroiditis are reported. Stimulated thyrocytes, oncocytes and degenerating thyrocytes were observed in all cases. Multinucleated thyrocytes and epithelial pseudogiant cells were identified in Hashimoto's disease only. Infiltrating lymphocytes, plasma cells, monocytes and macrophages were present in all cases. The ultrastructure of germinal centres was similar to that seen in lymphatic organs. Giant cells of both intra- and extrafollicular localization were seen in Hashimoto's disease. Most of the giant cells were macrophage-derived. Two different ways of giant cell formation were identified: besides the familiar dissolution of plasma membranes of adjacent macrophages, another mechanism of fusion was observed. At sites of contact, peculiar membrane structures were developed and disintegration of plasma membranes occurred in parts adjacent to these structures. These are not identical to desmosomes and are different from Langerhans' granules. They probably represent special organelles for the initiation of cellular fusion.

  5. Esophageal motor disorders in adults with eosinophilic esophagitis.

    Science.gov (United States)

    Moawad, Fouad J; Maydonovitch, Corinne L; Veerappan, Ganesh R; Bassett, John T; Lake, Jason M; Wong, Roy K H

    2011-05-01

    An association between eosinophilic esophagitis (EoE) and esophageal motility disorders has been described in small studies. The aim of this study was to describe the prevalence of esophageal motor disorders in a large cohort of adults with EoE and examine whether an association exists between esophageal dysmotility and dysphagia. A retrospective review of esophageal manometry studies in adult EoE patients was performed. Tracings were reviewed for abnormalities including nutcracker esophagus and ineffective swallows, defined as low amplitude peristalsis (esophagus was found in three patients. There was no significant difference in eosinophil count among the motility groups: normal 46.5 ± 3.1, mild IEM 56.9 ± 36.9, moderate IEM 45.5 ± 23.7, severe IEM 34.3 ± 12.6 (P = 0.157). In this cohort of EoE patients, the majority had normal esophageal motility studies, although a subset of these patients had some esophageal dysmotility. It is unlikely that esophageal dysmotility is a major contributing factor to dysphagia, although it is reasonable to consider esophageal manometry testing in EoE patients to identify potential abnormalities of the smooth muscle esophagus.

  6. Measurement of guinea pig eosinophil major basic protein by radioimmunoassay

    International Nuclear Information System (INIS)

    Wassom, D.L.; Loegering, D.A.; Gleich, G.J.

    1979-01-01

    Guinea pig eosinophil major basic protein (MBP) was measured by radioimmunoassay (RIA) using 131 I-MBP. Two critical features of the assay were: (1) alkylation of the MBP with iodoacetamide prior to radioiodination and (2) inclusion of another basic protein, either protamine or histone, in the phosphate buffer. Freshly isolated non-alkylated MBP was immunologically deficient when compared to alkylated or reduced MBP, but its reactivity could be redtores by reduction with dithiothreitol and alkylation. Reduction and alkylation also restored the immunoreactivity of polymerized MBP. MBP levels were not elevated in sera from guinea pigs parasitized with Trichinella spiralis and having peripheral blood eosinophilia. Muscle extracts from Trichinella infected animals showed significantly higher levels of MBP activity than normal controls. MBP was measurable in extracts of untreated eosinophils, but reduction and alkylation of these extracts increased MBP activity several fold. The RIA permits detection of MBP in body fluids and tissues at levels as low as 2 ng./ml. The RIA is useful in assessing increased or decreased levels of MBP activity in samples from experimental animals when compared to samples from controls. (author)

  7. Eosinophilic Esophagitis in Two Patients with Systemic Sclerosis

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    Tracy M. Frech

    2016-01-01

    Full Text Available The gastrointestinal tract (GIT is the most common extracutaneous organ system damaged in systemic sclerosis (SSc and is the presenting feature in 10% of patients. The esophagus as the portion of the GIT is the most commonly affected and there is an association of gastroesophageal reflux (GER with SSc interstitial lung disease (ILD. Thus, an aggressive treatment for GER is recommended in all SSc patients with ILD; however, it is recognized that a long-term benefit to this treatment is needed to understand its impact. In this case report we discuss the presence of eosinophilic esophagitis (EoE in two SSc patients and discuss the role for early EGD in SSc patients with moderate-severe GER symptoms for tissue study. Assessment of esophageal biopsy specimens for the presence of eosinophils and possibly ANA can help elucidate disease pathogenesis and direct therapy, as the presence of EoE in SSc has important management considerations, particularly with regards to dietary modification strategies.

  8. Elimination diets in the management of eosinophilic esophagitis.

    Science.gov (United States)

    Wechsler, Joshua B; Schwartz, Sally; Amsden, Katie; Kagalwalla, Amir F

    2014-01-01

    Eosinophilic esophagitis, an increasingly recognized chronic inflammatory disorder isolated to the esophagus, is triggered by an abnormal allergic response to dietary antigens. Current treatment includes swallowed topical steroids and dietary modification, which aim to resolve symptoms and prevent long-term complications such as formation of strictures. The dietary approach has become more widely accepted because long-term steroid therapy is associated with potential risks. Dietary treatment includes elemental and elimination diets. An exclusive elemental diet, which requires replacement of all intact protein with amino acid-based formula, offers the best response of all available therapies, with remission in up to 96% of subjects proving it to be superior to all other available therapies including topical steroids. However, compliance with this approach is challenging because of poor taste and monotony. The high cost of formula and the associated psychosocial problems are additional drawbacks of this approach. Empiric and allergy test-directed elimination diets have gained popularity given that elimination of a limited number of foods is much easier and as such is more readily acceptable. There is a growing body of literature supporting this type of therapy in both children and adults. This paper reviews the evidence for all types of dietary therapy in eosinophilic esophagitis.

  9. Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel

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    Ting Wen

    2017-07-01

    Full Text Available Eosinophilic esophagitis (EoE is a recently recognized upper gastrointestinal allergic disorder characterized by esophageal dysfunction (e.g., dysphagia and esophageal eosinophilia of ≥15 eosinophils/high-power field in patients who have persistent esophagitis even on proton pump inhibitor (PPI therapy. The histologic method is the gold standard of EoE diagnosis. However, EoE clinical symptoms do not always correlate with histology, and the histologic method has sensitivity and specificity issues due to the patchiness of EoE and the subjective nature of the method. The “EoE transcriptome” was initially discovered in 2006, which led to the invention of the EoE diagnostic panel (EDP. In addition to providing a definitive EoE diagnosis with high accuracy, the EDP has been useful in elucidating several key elements about the disease including the efficacy of specific drugs such as swallowed glucocorticoids and anti-IL-13 humanized antibody therapy, the relationship between EoE and PPI-responsive esophageal eosinophilia, and predicting the disease course and responsiveness to therapy. The EDP’s long-term potential arises from its plasticity to incorporate new genes and uncover novel disease pathogenesis. We expect that the EDP will be increasingly helpful for personalized medicine approaches and improved diagnostics and disease monitoring.

  10. Esophageal Rupture as a Primary Manifestation in Eosinophilic Esophagitis

    Directory of Open Access Journals (Sweden)

    Natalia Vernon

    2014-01-01

    Full Text Available Eosinophilic esophagitis (EoE is a chronic inflammatory process characterized by symptoms of esophageal dysfunction and, histologically, by eosinophilic infiltration of the esophagus. In adults, it commonly presents with dysphagia, food impaction, and chest or abdominal pain. Chronic inflammation can lead to diffuse narrowing of the esophageal lumen which may cause food impaction. Endoscopic procedures to relieve food impaction may lead to complications such as esophageal perforation due to the friability of the esophageal mucosa. Spontaneous transmural esophageal rupture, also known as Boerhaave’s syndrome, as a primary manifestation of EoE is rare. In this paper, we present two adult patients who presented with esophageal perforation as the initial manifestation of EoE. This rare complication of EoE has been documented in 13 other reports (11 adults, 2 children and only 1 of the patients had been previously diagnosed with EoE. A history of dysphagia was present in 1 of our patients and in the majority of previously documented patients. Esophageal perforation is a potentially severe complication of EoE. Patients with a history of dysphagia and patients with spontaneous esophageal perforation should warrant an evaluation for EoE.

  11. Methimazole associated eosinophilic pleural effusion: a case report.

    Science.gov (United States)

    Gaspar-da-Costa, Pedro; Duarte Silva, Filipa; Henriques, Júlia; do Vale, Sónia; Braz, Sandra; Meneses Santos, João; M M Victorino, Rui

    2017-03-21

    Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain. He had elevated C-reactive protein and erythrocyte sedimentation rate and normal white blood cell count and liver enzymes. Chest radiography showed a moderate right pleural effusion and the ultrasound revealed a loculated effusion that was shown to be an eosinophilic exudate. The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimazole. The thionamide was stopped and corticosteroid was started with complete resolution of the pleural effusion in 3 months. Awareness of this rare adverse reaction of anti-thyroid drugs is important and methimazole can be added to the list of possible etiologies of drug-induced eosinophilic pleural effusion.

  12. Lactic acid delays the inflammatory response of human monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peter, Katrin, E-mail: katrin.peter@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Rehli, Michael, E-mail: michael.rehli@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Singer, Katrin, E-mail: katrin.singer@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Renner-Sattler, Kathrin, E-mail: kathrin.renner-sattler@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Kreutz, Marina, E-mail: marina.kreutz@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany)

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

  13. Lactic acid delays the inflammatory response of human monocytes

    International Nuclear Information System (INIS)

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-01-01

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors

  14. Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors

    International Nuclear Information System (INIS)

    Ruemke, H.C.; Terpstra, F.G.; Huis, B.; Out, T.A.; Zeijlemaker, W.P.

    1982-01-01

    When human peripheral blood lymphocytes (PBL) are cultured in the presence of irradiated allogeneic lymphocytes, the resulting mixed lymphocyte reaction (MLR) leads to the secretion into the supernatant of substantial amounts of IgM and IgG, derived from nonirradiated responder B lymphocytes. Our data indicate that stimulation to Ig production by responder B cells may result from different types of of interactions. First, B cells and monocytes among the irradiated stimulator cells activate T responder B cells to produce Ig; second, ''responder'' B cells activate irradiated ''stimulator'' T cells, leading to a ''helper'' signal, back to the responder B cells and leading to Ig production. The latter system is radiosensitive, because allogeneic T cells, irradiated at a dose of 4000 rad or more, failed to induce Ig production by responder B cells. In some combinations of human allogeneic lymphocytes, the co-culture of the cells leads to inhibition of Ig production, both in the presence and in the absence of PWM. Thus, co-culture of allogeneic cells may cause ''positive'' as well as ''negative'' allogeneic effects. The implications of these findings for the interpretation of co-cultures that are aimed at establishing defects in lymphocytes from patients with, for example, immunodeficiencies, who fail to produce Ig in the presence of PWM are discussed

  15. PECAM-1 polymorphism affects monocyte adhesion to endothelial cells.

    Science.gov (United States)

    Goodman, Reyna S; Kirton, Christopher M; Oostingh, Gertie J; Schön, Michael P; Clark, Michael R; Bradley, J Andrew; Taylor, Craig J

    2008-02-15

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) plays an important role in leukocyte-endothelial cell adhesion and transmigration. Single nucleotide polymorphisms of PECAM-1 encoding amino acid substitutions at positions 98 leucine/valine (L/V), 536 serine/asparagine (S/N), and 643 arginine/glycine (R/G) occur in strong genetic linkage resulting in two common haplotypes (LSR and VNG). These PECAM-1 polymorphisms are associated with graft-versus-host disease after hematopoietic stem cell transplantation and with cardiovascular disease, but whether they influence PECAM-1 function is unknown. We examined the effect of homozygous and heterozygous expression of the PECAM-1 LSR and VNG genotypes on the adhesive interactions of peripheral blood monocytes and activated endothelial cell monolayers under shear stress in a flow-based cell adhesion assay. There was no difference in monocyte adhesion between the two homozygous genotypes of PECAM-1 but when monocytes expressed both alleles in heterozygous form, firm adhesion of monocytes to endothelial cells was markedly increased. PECAM-1 polymorphism expressed in homozygous or heterozygous form by endothelial cells did not influence monocyte adhesion. This is, to our knowledge, the first demonstration that PECAM-1 genotype can alter the level of monocyte binding to endothelial cells and a demonstration that heterozygous expression of a polymorphic protein may lead to altered function.

  16. Flow Cytometric Analysis of Leishmania Reactive CD4+/CD8+ Lymphocyte Proliferation in Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    H Keshavarz

    2008-12-01

    Full Text Available Background: Determination of the division history of T cells in vitro is helpful in the study of effector mechanisms against infections. Technique described here uses the intracellular fluorescent label carboxyfluorescein diacetate succinimidyl ester (CFSE to monitor the proliferation. Methods: In a cross sectional study, blood samples were collected from 7 volunteers with history of cutaneous leishmania­sis (CL and one healthy control from endemic areas in Isfahan province who referred to the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL, then CD4+/CD8+ lymphocytes and CD14+ monocytes were isolated from peri­pheral blood mononuclear cells (PBMC using mAbs and magnetic nanoparticles. CFSE labeled CD4+ or CD8+ lympho­cytes cultured with autologous monocytes in the presence of PHA, SLA, live Leishmania major or as control with­out sti­mulation. Cells were harvested after 7 days and were analyzed using flow cytometry. Results: Five consecutive divisions were monitored separately. Stimulation of CD4+ or CD8+ lymphocytes from CL sub­jects with SLA showed a significant difference in proliferation comparing with unstimulated cells (P< 0.05. The signifi­cant difference in the percentages of CD4+ cells stimulated with SLA was revealed at different divisions for each subject. In CD8+ lymphocyte, significant stronger stimulation of SLA was evident later in the proliferation process. The mean number of divisions in both CD4+/CD8+ lymphocytes stimulated with SLA was significantly greater than when stimulated with live L. major (P=0.007 / P=0.012, respectively Conclusion: The percentage of divided cells might be calculated separately in each division. The cells remained active following CFSE staining and there is possibility of functional analysis simultaneously.

  17. Eosinophil granule proteins ECP and EPX as markers for a potential early-stage inflammatory lesion in female genital schistosomiasis (FGS)

    DEFF Research Database (Denmark)

    Ramarokoto, Charles Emile; Kildemoes, Anna M. O.; Randrianasolo, Bodo Sahondra

    2014-01-01

    pathology, as viable schistosome egg granulomas often are eosinophil rich. Here it was investigated whether eosinophil granule proteins ECP (eosinophil cationic protein) and EPX (eosinophil protein-X) in urine and genital lavage can be used as markers for active FGS lesions. METHODS: Uro-genital samples...

  18. Successful Treatment For Chronic Eosinophilic Leukemia (CEL With Imatinib Mesylate

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    Rayane da Silva Souza

    2017-12-01

    Full Text Available We report a case of a patient with Chronic Eosinophilic Leukemia (CEL with mutation in alfa PDGFR gene exhibiting a satisfactory response to treatment with imatinib mesylate. A 25-year-old man presented in a hematology service with a persistent cough and hemogram alterations. His blood count showed a hemoglobin level of 12.5 g/dL and a white blood cell count of 94,030/mm3, eosinophils were 68% of all cells. Bone marrow aspiration and biopsy showed hypercellularity with marked eosinophilia (77% and erythroid differentiation series was hypocellular with normoblast maturation. The immunohistochemically of the bone biopsy was positive for myeloperoxidase and negative for CD34/CD99, consistent with CEL. Fluorescence in situ hybridization (FISH for the beta-fraction of platelet-derived growth factor (PDGFRβ and Philadelphia chromosome (Ph 1 were negative and the alfa PDGFR (Platelet-Derived Growth Factor was positive and showed heterozygosis in c.2531T>C on 18 Exon and homozygous in C.2562+1G>A at the region of the splicing site at the 18 intron. Treatment was initiated and maintained by administering 400mg/day imatinib mesylate. Laboratory findings returned to normal ranges, with clinical improvement and a hematological response observed after the second month of therapy. Currently, the patient’s blood count shows the white blood cell count (5,400 total leukocytes, eosinophils (8.6/mm3, hemoglobin (15.5 g/dl, hematocrit (45.4% and platelets (298,000/mm3 within normal ranges. The mutation search was negative in in peripheral blood one year after the initial treatment. Our work corroborates other studies on the efficacy of imatinib mesylate in the treatment of patients with CSF PDGFR alpha positive. We emphasize the importance of molecular studies, considering its relevance for the correct staging of the disease. Since CEL is a rare disease, it is important to define its etiology and anticipate its treatment, thus minimizing the damage induced by

  19. Severe Rhabdomyolysis without Systemic Involvement: A Rare Case of Idiopathic Eosinophilic Polymyositis

    Directory of Open Access Journals (Sweden)

    Ayesha Farooq

    2015-01-01

    Full Text Available Introduction. Eosinophilic polymyositis (EPM is a rare cause of rhabdomyolysis characterized by eosinophilic infiltrates in the muscle. We describe the case of a young patient with eosinophilic polymyositis causing isolated severe rhabdomyolysis without systemic involvement. Case Presentation. A 22-year-old Haitian female with no past medical history presented with progressive generalized muscle aches without precipitating factors. Examination of the extremities revealed diffuse muscle tenderness. Laboratory findings demonstrated peripheral eosinophilia and high creatinine phosphokinase (CPK and transaminase levels. Workup for the common causes of rhabdomyolysis were negative. Her CPK continued to rise to greater than 100,000 units/L so a muscle biopsy was performed which showed widespread eosinophilic infiltrate consistent with eosinophilic polymyositis. She was started on high dose systemic corticosteroids with improvement of her symptoms, eosinophilia, and CPK level. Discussion. This case illustrates a systematic workup of rhabdomyolysis in the presence of peripheral eosinophilia. Many differential diagnoses must be considered before establishing a diagnosis of idiopathic eosinophilic polymyositis. To our knowledge, our case of eosinophilic polymyositis is unique as it presented with severe rhabdomyolysis without another organ involvement. Clinicians should maintain a high index of suspicion for this physically debilitating disease to aid in prompt diagnosis.

  20. TLR-Stimulated Eosinophils Mediate Recruitment and Activation of NK Cells In Vivo.

    Science.gov (United States)

    O'Flaherty, S M; Sutummaporn, K; Häggtoft, W L; Worrall, A P; Rizzo, M; Braniste, V; Höglund, P; Kadri, N; Chambers, B J

    2017-06-01

    Eosinophils like many myeloid innate immune cells can provide cytokines and chemokines for the activation of other immune cells upon TLR stimulation. When TLR-stimulated eosinophils were inoculated i.p. into wild-type mice, and NK cells were rapidly recruited and exhibited antitumour cytotoxicity. However, when mice depleted of CD11c + cells were used, a marked decrease in the number of recruited NK cells was observed. We postulated that CpG or LPS from the injected eosinophils could be transferred to host cells, which in turn could recruit NK cells. However, by inoculating mice deficient in TLR4 or TLR9 with LPS or CpG-stimulated eosinophils respectively, NK cell recruitment was still observed alongside cytotoxicity and IFNγ production. CpG stimulation of eosinophils produced the pro-inflammatory cytokine IL-12 and the chemokine CXCL10, which are important for NK cell activation and recruitment in vivo. To demonstrate the importance of CXCL10 in NK cell recruitment, we found that CpG-stimulated eosinophils pretreated with the gut microbial metabolite butyrate had reduced expression and production of CXCL10 and IL-12 and concomitantly were poor at recruitment of NK cells and inducing IFNγ in NK cells. Therefore, eosinophils like other innate immune cells of myeloid origin can conceivably stimulate NK cell activity. In addition, products of the gut microbiota can be potential inhibitors of NK cell. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  1. Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

    Science.gov (United States)

    Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

    2017-03-01

    Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

  2. The expanding role(s) of eosinophils in health and disease

    Science.gov (United States)

    Jacobsen, Elizabeth A.; Helmers, Richard A.

    2012-01-01

    Surprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review argues that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrates that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy persons. We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement “Did you know …?” PMID:22936660

  3. Synergic production of neutrophil chemotactic activity by colonic epithelial cells and eosinophils.

    Science.gov (United States)

    Dent, Gordon; Loweth, Sam C; Hasan, Anwar Matar; Leslie, Fiona M

    2014-10-01

    The presence of eosinophils in the lumen and mucosa of the intestine is characteristic of both ulcerative colitis (UC) and Crohn's disease (CD). There is evidence of eosinophil activation in the intestine during acute inflammatory episodes of these diseases; these episodes are also characterized by an influx of neutrophils, which have the potential to cause extensive tissue damage. We undertook a study to determine whether eosinophils in contact with colonic epithelial cells produce factors that may attract neutrophils in response to immunological stimulation. Neutrophil chemotactic activity (NCA) and concentrations of three neutrophil-attracting CXC chemokines - CXCL1 (Groα), CXCL5 (Ena78) and CXCL8 (IL8) - were measured in supernatants of T84 colonic epithelial cells and blood eosinophils or eosinophil-like myeloid leukaemia cells (AML14.3D10), alone or in combination. Cells were stimulated with serum-opsonized zymosan (OZ) particles. NCA (Peosinophil co-cultures were significantly higher than in the supernatants of either cell type alone. Release of CXCL1 (Peosinophils but not higher than from OZ-stimulated epithelial cells. Eosinophils and colonic epithelial cells exhibit synergy in production of neutrophil chemoattractants in response to immunological stimulation. This may represent a mechanism for exaggerated recruitment of neutrophils to the intestine in response to acute infection in conditions that are characterized by the presence of eosinophils in the bowel. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. Antibody-secreting cells in respiratory tract tissues in the absence of eosinophils as supportive partners.

    Science.gov (United States)

    Sealy, Robert E; Surman, Sherri L; Vogel, Peter; Hurwitz, Julia L

    2016-11-01

    Antibody-secreting cells (ASCs) in respiratory tract tissues provide a first line of defense against invading pathogens. These cells often secrete IgA that is efficiently transcytosed across epithelial barriers into the airway lumen where pathogens can be blocked at their point of entry. Previous literature has reported that in the bone marrow, eosinophils are required for the maintenance of ASCs, and that eosinophils co-localize with ASCs as nearest neighbors. To determine if these rules similarly apply to the maintenance of ASCs in respiratory tract tissues, we evaluated virus-specific responses 1 month and 4 months following an intranasal virus infection of eosinophil-null (∆dblGATA-1) mice. Results showed that ASCs were fractionally reduced, but were nonetheless observed in respiratory tract tissues in the absence of eosinophils. Virus-specific antibodies were similarly observed in the airways of eosinophil-deficient mice. Respiratory tract ASCs were also present in mice lacking neutrophils (Mcl1 ∆M ). The staining of tissue sections from the upper respiratory tract of wild-type mice following viral infections demonstrated that virus-specific ASCs were most frequently situated adjacent to epithelial cells rather than eosinophils or neutrophils. Taken together, these data emphasize that rules for cell maintenance are not absolute and that ASCs can survive in the respiratory tract without eosinophils or neutrophils as their nearest neighbors. © The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Elevated Systemic Levels of Eosinophil, Neutrophil, and Mast Cell Granular Proteins in Strongyloides Stercoralis Infection that Diminish following Treatment.

    Science.gov (United States)

    Rajamanickam, Anuradha; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandra Kumar; Nutman, Thomas B; Babu, Subash

    2018-01-01

    Infection with the helminth parasite Strongyloides stercoralis ( Ss ) is commonly clinically asymptomatic that is often accompanied by peripheral eosinophilia. Granulocytes are activated during helminth infection and can act as immune effector cells. Plasma levels of eosinophil and neutrophil granular proteins convey an indirect measure of granulocyte degranulation and are prominently augmented in numerous helminth-infected patients. In this study, we sought to examine the levels of eosinophil, neutrophil, and mast cell activation-associated granule proteins in asymptomatic Ss infection and to understand their kinetics following anthelmintic therapy. To this end, we measured the plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, neutrophil elastase, myeloperoxidase, neutrophil proteinase-3, mast cell tryptase, leukotriene C4, and mast cell carboxypeptidase-A3 in individuals with asymptomatic Ss infection or without Ss infection [uninfected (UN)]. We also estimated the levels of all of these analytes in infected individuals following definitive treatment of Ss infection. We demonstrated that those infected individuals have significantly enhanced plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, elastase, myeloperoxidase, mast cell tryptase, leukotriene C4, and carboxypeptidase-A3 compared to UN individuals. Following the treatment of Ss infection, each of these granulocyte-associated proteins drops significantly. Our data suggest that eosinophil, neutrophil, and mast cell activation may play a role in the response to Ss infection.

  6. Isolation of monocytes from leukapheretic products for large-scale GMP-grade generation of cytomegalovirus-specific T-cell lines by means of an automated elutriation device.

    Science.gov (United States)

    Perseghin, Paolo; D'Amico, Giovanna; Dander, Erica; Gaipa, Giuseppe; Dassi, Maria; Biagi, Ettore; Biondi, Andrea

    2008-08-01

    Dendritic cells (DC) act as antigen-presenting cells in immune response-mediated mechanisms against malignant cells and/or viral or fungal pathogens. CD14+ monocytes have been so far isolated by techniques of plastic adherence or by using immunomagnetic methods. Here the effectiveness of a commercially available cell separation system (Elutra, Gambro BCT) in the separation of monocytes and the large-scale production of cytomegalovirus (CMV)-specific T-cell lines were investigated. Six mononuclear cell (MNC) collections were processed with the Elutra system. Monocyte-enriched fraction was differentiated into DCs by addition of granulocyte-macrophage-colony-stimulating factor and interleukin (IL)-4. After 6 days of culture, DCs were matured in the presence of interferon (IFN)-gamma, IFN-alpha, IL-1beta, tumor necrosis factor-alpha, and poly(I:C) and pulsed with a pool of 48 MHC Class I and II-binding CMV peptides. Lymphocytes were then stimulated with mature autologous CMV peptide-pulsed DCs. After elutriation, the mean monocyte yield was 0.89 x 10(9) +/- 0.65 x 10(9), with a 51.0 +/- 31.6 percent recovery and a 51.1 +/- 35.4 percent purity. A significant correlation was observed when basal monocyte content was related to the postelutriation recovery (p < 0.0116). More than 60 percent of plated monocytes were differentiated into DCs, which after pulsing with CMV peptides, were able to stimulate a robust enrichment in CMV antigen-specific T cells in all tested samples (mean percentage of pentamer-positive CD8+ cells, 35% compared to the initial 2%). Our findings might be helpful for an appropriate MNC collection, to maximize the efficiency of the elutriation system and subsequently obtain an optimal monocyte-enriched yield for further DC generation and T-cell stimulation.

  7. Lymphocytic esophagitis: Report of three cases and review of the literature

    Science.gov (United States)

    Jideh, Bilel; Keegan, Andrew; Weltman, Martin

    2016-01-01

    Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema (“spongiosis”). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn’s disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. LyE has been reported to run a benign course; however there has been a case of esophageal perforation associated with LyE. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature. PMID:28035315

  8. STAT3 activation in monocytes accelerates liver cancer progression

    International Nuclear Information System (INIS)

    Wu, Wen-Yong; Li, Jun; Wu, Zheng-Sheng; Zhang, Chang-Le; Meng, Xiang-Ling

    2011-01-01

    Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor ubiquitously expressed in different cell types. STAT3 plays an essential role in cell survival, proliferation, and differentiation. Aberrantly hyper-activated STAT3 signaling in cancer cells and in the tumor microenvironment has been detected in a wide variety of human cancers and is considered an important factor for cancer initiation, development, and progression. However, the role of STAT3 activation in monocytes in the development of HCC has not been well understood. Immunohistochemical analysis of phosphorylated STAT3 was performed on tissue microarray from HCC patients. Using a co-culture system in vivo, HCC cell growth was determined by the MTT assay. In vivo experiments were conducted with mice given diethylinitrosamine (DEN), which induces HCC was used to investigate the role of STAT3 expression in monocytes on tumor growth. Real-time PCR was used to determine the expression of cell proliferation and cell arrest associated genes in the tumor and nontumor tissue from liver. Phosphorylated STAT3 was found in human hepatocellular carcinoma tissue samples and was expressed in tumor cells and also in monocytes. Phosphorylated STAT3 expression in monocyte was significantly correlated to advanced clinical stage of HCC and a poor prognosis. Using a co-culture system in vivo, monocytes promoted HCC cell growth via the IL-6/STAT3 signaling pathway. The STAT3 inhibitor, NSC 74859, significantly suppressed tumor growth in vivo in mice with diethylinitrosamine (DEN)-induced HCC. In this animal model, blockade of STAT3 with NSC 74859 induced tumor cell apoptosis, while inhibiting both tumor cells and monocytes proliferation. Furthermore, NSC 74859 treatment suppressed cancer associated inflammation in DEN-induce HCC. Our data suggest constitutively activated STAT3 monocytes promote liver tumorigenesis in clinical patients and animal experiments. Thus, STAT3 in tumor

  9. Mycobacterium leprae alters classical activation of human monocytes in vitro.

    Science.gov (United States)

    Fallows, Dorothy; Peixoto, Blas; Kaplan, Gilla; Manca, Claudia

    2016-01-01

    Macrophages play a central role in the pathogenesis of leprosy, caused by Mycobacterium leprae. The polarized clinical presentations in leprosy are associated with differential immune activation. In tuberculoid leprosy, macrophages show a classical activation phenotype (M1), while macrophages in lepromatous disease display characteristics of alternative activation (M2). Bacille Calmette-Guérin (BCG) vaccination, which protects against leprosy, can promote sustained changes in monocyte response to unrelated pathogens and may preferentially direct monocytes towards an M1 protective phenotype. We previously reported that M. leprae can dampen the response of naïve human monocytes to a strong inducer of pro-inflammatory cytokines, such as BCG. Here, we investigated the ability of the pathogen to alter the direction of macrophage polarization and the impact of BCG vaccination on the monocyte response to M. leprae. We show that in vitro exposure of monocytes from healthy donors to M. leprae interferes with subsequent M1 polarization, indicated by lower levels of M1-associated cytokine/chemokines released and reduced expression of M1 cell surface markers. Exposure to M. leprae phenolic glycolipid (PGL) 1, instead of whole bacteria, demonstrated a similar effect on M1 cytokine/chemokine release. In addition, we found that monocytes from 10-week old BCG-vaccinated infants released higher levels of the pro-inflammatory cytokines TNF-α and IL-1β in response to M. leprae compared to those from unvaccinated infants. Exposure to M. leprae has an inhibitory effect on M1 macrophage polarization, likely mediated through PGL-1. By directing monocyte/macrophages preferentially towards M1 activation, BCG vaccination may render the cells more refractory to the inhibitory effects of subsequent M. leprae infection.

  10. Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma.

    Science.gov (United States)

    Koh, Y I; Choi, S

    2002-02-01

    It has been suggested that airway eosinophilic inflammation is associated with the severity of exercise-induced bronchospasm (EIB). Blood eosinophils are known to be an indirect marker of airway inflammation in asthma. The aim of this study is to investigate that a simple and easy blood test for blood eosinphil counts may predict the severity of EIB in asthma. Seventy-seven men with perennial asthma (age range 18-23 years) were included. Lung function test, skin prick test, and blood tests for eosinophils counts and total IgE levels were performed. Methacholine bronchial provocation test and, 24 h later, free running test were carried out. EIB was defined as a 15% reduction or more in post-exercise FEV1 compared with pre-exercise FEV1 value. Atopy score was defined as a sum of mean wheal diameters to allergens. EIB was observed in 60 (78%) of 77 subjects. Asthmatics with EIB showed significantly increased percentages of eosinophils (P 700 microl(-1) (36.9 +/- 12.7%) had significantly greater maximal % fall in FEV1 after exercise than asthmatics with eosinophils of 350 microl(-1) yielded the specificity of 88% and positive predictive value of 93% for the presence of EIB. When a multiple regression analysis of maximal % fall in FEV1 according to log eosinophil counts, log PC20, log IgE and atopy score was performed, only blood eosinophil counts were significant factor contributing to the maximal % fall in FEV1 after exercise. These findings not only suggest that a simple blood test for eosinophils may be useful in the prediction of the severity of EIB, but also reinforce the view that airway eosinophilic inflammation may play a major role in EIB in asthma.

  11. Eosinophil Resistance to Glucocorticoid-Induced Apoptosis is Mediated by the Transcription Factor NFIL3

    Science.gov (United States)

    Pazdrak, Konrad; Moon, Young; Straub, Christof; Stafford, Susan; Kurosky, Alexander

    2016-01-01

    The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired prop-aptoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex). IL-5-activated eosinophils showed contrasting responses to CpdA and Dex, as IL-5-treated eosinophils showed no increase in apoptosis compared to cells treated with Dex alone, while CpdA elicited an apoptotic response regardless of IL-5 stimulation. Proteomic analysis revealed that both Nuclear Factor IL-3 (NFIL3) and Map Kinase Phosphatase 1 (MKP1) were inducible by IL-5 and enhanced by Dex; however, CpdA had no effect on NFIL3 and MKP1 expression. We found that inhibiting NFIL3 with specific siRNA or by blocking the IL-5-inducible Pim-1 kinase abrogated the protective effect of IL-5 on Dex-induced apoptosis, indicating crosstalk between IL-5 anti-apoptotic pathways and GR-mediated TA signaling occurring via the NFIL3 molecule. Collectively, these results indicate that 1) GCs' TA pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3; and 2) functional inhibition of IL-5 signaling (anti-Pim1) or the use of selective GR agonists that don't upregulate NFIL3 may be effective strategies for the restoring pro-apoptotic effect of GCs on IL-5-activated eosinophils. PMID:26880402

  12. Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

    Science.gov (United States)

    de Graauw, E; Sitaru, C; Horn, M; Borradori, L; Yousefi, S; Simon, H-U; Simon, D

    2017-07-01

    Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab') 2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P eosinophil extracellular trap (EET) formation (P = 0.048). Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodi