中性粒细胞胞外诱捕网与肺部炎症性疾病的关系
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摘要
中性粒细胞募集/浸润是肺部炎症性疾病的特征性表现,是肺部抵抗病原微生物入侵的第一道防线,主要通过吞噬作用杀灭病原微生物.然而,新近的研究发现,中性粒细胞被刺激后可形成一种以DNA为骨架并镶嵌有大量活性蛋白质的网状物质——中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs),这种特殊形式的生物结构能捕获并杀灭病原微生物.尽管就NETs的生物学功能而言,其对肺部炎症性疾病应该是有益的,但是越来越多的研究表明,NETs对肺上皮细胞和内皮细胞均具有直接的细胞毒性作用,并可能促进肺部炎症性疾病的发生发展.为了系统地了解NETs与肺部相关炎症性疾病的关系,本综述首先简述了NETs的结构、功能和形成过程,然后分别叙述了NETs与哮喘、慢性阻塞性肺病、细菌性肺炎、肺结核、肺囊性纤维化、间质性肺疾病、流感病毒感染和急性肺损伤的关系.最后总结、展望了NETs在肺部炎症性疾病中的潜在研究方向和针对性治疗策略.
Neutrophil recruitment/infiltration is a characteristic manifestation of pulmonary inflammatory diseases and is the first line of defense against pathogenic microbial invasion in the lungs, killing pathogenic microorganisms mainly through phagocytosis. However, new research has found that neutrophils can form a network called neutrophil extracellular traps(NETs) that are DNA-based and inlaid with a large amount of active protein. This biological structure can capture and kill pathogenic microorganisms. Although it is beneficial for lung inflammatory diseases in terms of the biological function of NETs, more and more studies have shown that NETs have direct cytotoxic effects on lung epithelial cells and endothelial cells, and may promote the lung inflammatory diseases. In order to systematically understand the relationship between NETs and lung-related inflammatory diseases, this review first briefly describes the structure, function and formation process of NETs,and then describes the relationship of NETs and asthma, chronic obstructive pulmonary disease, bacterial pneumonia, tuberculosis, cystic fibrosis, interstitial lung disease, influenza virus infection and acute lung injury,finally summarizes the potential research directions and targeted treatment strategies of NETs in pulmonary inflammatory diseases.
Neutrophil recruitment/infiltration is a characteristic manifestation of pulmonary inflammatory diseases and is the first line of defense against pathogenic microbial invasion in the lungs, killing pathogenic microorganisms mainly through phagocytosis. However, new research has found that neutrophils can form a network called neutrophil extracellular traps(NETs) that are DNA-based and inlaid with a large amount of active protein. This biological structure can capture and kill pathogenic microorganisms. Although it is beneficial for lung inflammatory diseases in terms of the biological function of NETs, more and more studies have shown that NETs have direct cytotoxic effects on lung epithelial cells and endothelial cells, and may promote the lung inflammatory diseases. In order to systematically understand the relationship between NETs and lung-related inflammatory diseases, this review first briefly describes the structure, function and formation process of NETs,and then describes the relationship of NETs and asthma, chronic obstructive pulmonary disease, bacterial pneumonia, tuberculosis, cystic fibrosis, interstitial lung disease, influenza virus infection and acute lung injury,finally summarizes the potential research directions and targeted treatment strategies of NETs in pulmonary inflammatory diseases.
引文
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[33]Tashkin D P,Murray R P.Smoking cessation in chronic obstructive pulmonary disease.Respir Med,2009,103(7):963-974
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[35]Sabbione F,Keitelman I A,Iula L,et al.Neutrophil extracellular traps stimulate proinflammatory responses in human airway epithelial cells.J Innate Immun,2017,9(4):387-402
[36]Qiu S L,Zhang H,Tang Q Y,et al.Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells.Thorax,2017,72(12):1084-1093
[37]Zou Y,Chen X,Xiao J,et al.Neutrophil extracellular traps promote lipopolysaccharide-induced airway inflammation and mucus hypersecretion in mice.Oncotarget,2018,9(17):13276-13286
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[41]Mori Y,Yamaguchi M,Terao Y,et al.alpha-Enolase of Streptococcus pneumoniae induces formation of neutrophil extracellular traps.J Biol Chem,2012,287(13):10472-10481
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