中性粒细胞胞外陷阱
中性粒细胞弹性蛋白酶
特发性肺纤维化
纤维化
免疫学
医学
骨髓
肺
趋化因子
髓过氧化物酶
炎症
肺纤维化
弹性蛋白酶
病理
生物
内科学
酶
生物化学
作者
Helen Warheit-Niemi,Gabrielle P Huizinga,Summer J. Edwards,Yizhou Wang,Susan Murray,David N. O’Dwyer,Bethany B. Moore
出处
期刊:ImmunoHorizons
[The American Association of Immunologists]
日期:2022-12-01
卷期号:6 (12): 817-834
标识
DOI:10.4049/immunohorizons.2200083
摘要
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible disease characterized by collagen deposition within the interstitium of the lung. This impairs gas exchange and results in eventual respiratory failure. Clinical studies show a correlation between elevated neutrophil numbers and IPF disease progression; however, the mechanistic roles neutrophils play in this disease are not well described. In the present study, we describe alterations to the trafficking and function of neutrophils after the development of fibrosis. We observed increased numbers of total and aged neutrophils in peripheral tissues of fibrotic mice. This appeared to be driven by an upregulation of neutrophil chemokine Cxcl2 by lung cells. In addition, neutrophil recruitment back to the bone marrow for clearance appeared to be impaired, because we saw decreased aged neutrophils in the bone marrow of fibrotic mice. Neutrophils in fibrosis were activated, because ex vivo assays showed increased elastase and extracellular trap release by neutrophils from fibrotic mice. This likely mediated disease exacerbation, because mice exhibiting a progressive disease phenotype with greater weight loss and mortality had more activated neutrophils and increased levels of extracellular DNA present in their lungs than did mice with a nonprogressive disease phenotype. These findings further our understanding of the dynamics of neutrophil populations and their trafficking in progressive fibrotic lung disease and may help inform treatments targeting neutrophil function for patients with IPF experiencing disease exacerbation in the future.
科研通智能强力驱动
Strongly Powered by AbleSci AI