Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis
- PMID: 28916704
- PMCID: VSports在线直播 - PMC5771859
- DOI: 10.1136/thoraxjnl-2017-210134
"V体育平台登录" Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis
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Background: Cystic fibrosis (CF) lung disease is defined by large numbers of neutrophils and associated damaging products in the airway. Delayed neutrophil apoptosis is described in CF although it is unclear whether this is a primary neutrophil defect or a response to chronic inflammation. Increased levels of neutrophil extracellular traps (NETs) have been measured in CF and we aimed to investigate the causal relationship between these phenomena and their potential to serve as a driver of inflammation. We hypothesised that the delay in apoptosis in CF is a primary defect and preferentially allows CF neutrophils to form NETs, contributing to inflammation. VSports手机版.
Methods: Blood neutrophils were isolated from patients with CF, CF pigs and appropriate controls. Neutrophils were also obtained from patients with CF before and after commencing ivacaftor. Apoptosis was assessed by morphology and flow cytometry. NET formation was determined by fluorescent microscopy and DNA release assays. NET interaction with macrophages was examined by measuring cytokine generation with ELISA and qRT-PCR. V体育安卓版.
Results: CF neutrophils live longer due to decreased apoptosis. This was observed in both cystic fibrosis transmembrane conductance regulator (CFTR) null piglets and patients with CF, and furthermore was reversed by ivacaftor (CFTR potentiator) in patients with gating (G551D) mutations V体育ios版. CF neutrophils formed more NETs and this was reversed by cyclin-dependent kinase inhibitor exposure. NETs provided a proinflammatory stimulus to macrophages, which was enhanced in CF. .
Conclusions: CF neutrophils have a prosurvival phenotype that is associated with an absence of CFTR function and allows increased NET production, which can in turn induce inflammation VSports最新版本. Augmenting neutrophil apoptosis in CF may allow more appropriate neutrophil disposal, decreasing NET formation and thus inflammation. .
Keywords: Cystic Fibrosis; Neutrophil Biology V体育平台登录. .
© 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 VSports注册入口. .
Conflict of interest statement (VSports在线直播)
Competing interests: None declared.
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References
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- Morgan WJ, Butler SM, Johnson CA, et al. . Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada. Pediatr Pulmonol 1999;28:231–41. 10.1002/(SICI)1099-0496(199910)28:4<231::AID-PPUL1>3.0.CO;2-2 - DOI - PubMed
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