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Osric A. Forrest Daniel M. Chopyk Yael Gernez Milton R. Brown Carol K. Conrad Richard B. Moss Vin Tangpricha Limin Peng Rabindra Tirouvanziam 《Journal of cystic fibrosis》2019,18(1):64-70
Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献4.
Alice Bertocchi Sara Carloni Paola Simona Ravenda Giovanni Bertalot Ilaria Spadoni Antonino Lo Cascio Sara Gandini Michela Lizier Daniele Braga Francesco Asnicar Nicola Segata Chris Klaver Paola Brescia Elio Rossi Achille Anselmo Silvia Guglietta Annalisa Maroli Paola Spaggiari Maria Rescigno 《Cancer cell》2021,39(5):708-724.e11
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Leishmaniasis is a neglected infectious disease with clinical presentations ranging from asymptomatic or mild symptoms to chronic infection and eventual death. The mechanisms of disease susceptibility and pathology have been extensively studied, but there are no steadfast rules regarding leishmaniasis. A Th1 response is usually associated with infection control, while a predominant Th2 response is detrimental to the patient. In this scenario, the enzymes arginase and inducible nitric oxide synthase represent two possible pathways of immune response. While the former contributes to parasite replication, the latter is crucial for its control. In the present review, we collected study results that associate arginase expression in patients and in experimental models with disease susceptibility/chronicity and show some proposed mechanisms that explain the role of arginase in maintaining Leishmania infection, including polyamine and thiol synthesis, tissue-resident macrophage (TRM) proliferation and activation and T-cell suppression and exhaustion. 相似文献
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J. Ventura‐Juarez MR. Campos‐Esparza J. Pacheco‐Yepez J. A López‐Blanco A. Adabache‐Ortíz M. Silva‐Briano R. Campos‐Rodríguez 《Parasite immunology》2016,38(8):503-509
Entamoeba histolytica invades the intestine and other organs during the pathogenesis of amoebiasis. In the early stages, the host organism responds with an inflammatory infiltrate composed mostly of neutrophils. It has been reported that these immune cells, activated by E. histolytica, exert a protective role by releasing proteolytic enzymes and generating reactive oxygen/nitrogen species (ROS/RNS) and antimicrobial peptides. It is now known that neutrophils also produce neutrophil extracellular traps (NETs), which are able to damage and kill pathogens. Studies have shown that intracellular protozoan pathogens, including Toxoplasma gondi, Plasmodium falciparum and Leishmania spp, induce neutrophils to release NETs and are damaged by them. However, the action of this mechanism has not been explored in relation to E. histolytica trophozoites. Through scanning electron, epifluorescence microscopy and viability assays, we show for first time that during in vitro interaction with E. histolytica trophozoites, human neutrophils released NETs that covered amoebas and reduced amoebic viability. These NETs presented histones, myeloperoxidase and decondensed chromatin. The results suggest that NETs participate in the elimination of the parasite. 相似文献
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目的观察难治性慢性丙型肝炎标准治疗过程中血常规的变化与抗病毒疗效的关系。方法收集2011年9月-2012年12月于首都医科大学附属北京佑安医院就诊的难治性慢性丙型肝炎初治患者63例,给予聚乙二醇干扰素α-2a(180μg/周)联合利巴韦林治疗48周,分别在基线、治疗4、12、24、48周和随访24周时进行HCV RNA及血常规的检测,分析血常规与疗效的相关性。根据是否获得持续病毒学应答(SVR),分为SVR组和n SVR组。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验;采用简单线性相关分析法进行相关性分析。结果 63例患者有3例失访,余下60例均完成抗病毒治疗和24周随访,其中46例获得SVR,SVR率为76.7%;SVR组患者治疗4、12、24周时的淋巴细胞计数(LYPH)、白细胞计数(WBC)及中性粒细胞计数(NUET)均低于n SVR组,并且在12周时差异均有统计学意义(t值分别为3.398、2.766、2.037,P值均0.05),在24周时两组WBC及NUET差异亦均有统计学意义(t值分别为2.559、2.151,P值均0.05);此外SVR组患者在治疗4周时上述3项指标较基线的下降幅度均大于n SVR组,其中LYPH下降幅度在两组间差异有统计学意义(t=2.26,P=0.03)。LYPH、WBC、NUET在治疗4、12周时与HCV RNA的下降幅度呈正相关(r值分别为0.36、0.45、0.37、0.47、0.61、0.33,P值均0.05)。结论血常规中LYPH、WBC及NEUT的变化及下降幅度在一定程度上可作为难治性慢性丙型肝炎抗病毒疗效的预测指标。 相似文献
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Kian Fan Chung 《Journal of internal medicine》2016,279(2):192-204
Asthma is a common heterogeneous disease with a complex pathophysiology that carries a significant mortality rate and high morbidity. Current therapies based on inhaled corticosteroids and long‐acting β‐agonists remain effective in a large proportion of patients with asthma, but ~10% (considered to have ‘severe asthma’) do not respond to these treatments even at high doses or with the use of oral corticosteroids. Analytical clustering methods have revealed phenotypes that include dependence on high‐dose corticosteroid treatment, severe airflow obstruction and recurrent exacerbations associated with an allergic background and late onset of disease. One severe phenotype is eosinophilic inflammation‐predominant asthma, with late‐onset disease, rhinosinusitis, aspirin sensitivity and exacerbations. Blood and sputum eosinophilia have been used to distinguish patients with high Th2 inflammation and to predict therapeutic response to treatments targeted towards Th2‐associated cytokines. New therapies in the form of humanized antibodies against Th2 targets, such as anti‐IgE, anti‐IL4Rα, anti‐IL‐5 and anti‐IL‐13 antibodies, have shown encouraging results in terms of reduction in exacerbations and improvement in airflow in patients with a ‘Th2‐high’ expression profile and blood eosinophilia. Research efforts are now focusing on elucidating the phenotypes underlying the non‐Th2‐high (or Th2‐low) group, which constitutes ~50% of severe asthma cases. There is an increasing need to use biomarkers to indicate the group of patients who will respond to a specifically targeted treatment. The use of improved tools to measure activity of disease, a better definition of severe asthma and the delineation of inflammatory pathways with omics analyses using computational tools, will lead to better‐defined phenotypes for specific therapies. 相似文献