中性粒细胞胞外诱捕网在急性肺损伤及急性呼吸窘迫综合征气道炎症中的研究进展

Progress of neutrophil extracellular traps in airway inflammation of acute lung injury/acute respiratory distress syndrome:Review

急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是由多种因素导致的急性、进行性加重的弥漫性炎症性肺损伤,最终引起呼吸功能不全或呼吸衰竭的临床表现。在多种刺激因子作用下,炎症环境中活化的中性粒细胞可释放包含基因组DNA、组蛋白、髓过氧化物酶、中性粒细胞弹性蛋白酶、瓜氨酸化组蛋白和组织蛋白酶在内的多种成分,上述物质构成的纤维网状结构即中性粒细胞胞外诱捕网;后者的过量产生参与肺组织炎症损伤的病理过程。我们通过对中性粒细胞胞外诱捕网的基本特征、产生机制、在肺部炎症中的调控作用,以及以中性粒细胞胞外诱捕网的形成通路、构成组分为靶点治疗ALI/ARDS的可能性等研究内容进行总结和分析,为研发治疗肺部炎症损伤的潜在药物提供新的思路。

Acute lung injury(ALI)or acute respiratory distress syndrome(ARDS)is defined as pulmonary diffuse inflammatory injury characterized by acute onset and progressive exacerbation,which is caused by various factors and leads to respiratory insufficiency or respiratory failure eventually.In response to a variety of stimulis,activated neutrophils can release many components including genomic DNA,histones,myeloperoxidase,neutrophil elastase,citrullinated histones,and cathepsins to the inflammatory environment.All the above substances constitute a fibrous meshwork that is named neutrophil extracellular traps(NETs).The overproduction of the NETs is involved in the inflammatory injury in lung tissues.We reviewed the basic features of NETs and its generation mechanism as well as regulatory role in lung inflammation.Besides,we analyzed the components and celluar singal pathway involed in the formation of NETs in order to find appropriate therapeutic targets,which would shed light on developing potential drugs and designing new strategies.