上睑下垂
炎症
溶解循环
坏死性下垂
程序性细胞死亡
蛋白酵素
免疫学
细胞凋亡
传出细胞增多
免疫系统
中性粒细胞胞外陷阱
细胞生物学
巨噬细胞
生物
炎症体
病毒
体外
酶
生物化学
作者
Apurwa Singhal,Sachin Kumar
出处
期刊:Immunology
[Wiley]
日期:2021-11-09
卷期号:165 (1): 22-43
被引量:42
摘要
Neutrophil-centred inflammation and flawed clearance of neutrophils cause and exuberate multiple pathological conditions. These most abundant leukocytes exhibit very high daily turnover in steady-state and stress conditions. Various armours including oxidative burst, NETs and proteases function against pathogens, but also dispose neutrophils to spawn pro-inflammatory responses. Neutrophils undergo death through different pathways upon ageing, infection, executing the intruder's elimination. These include non-lytic apoptosis and other lytic deaths including NETosis, necroptosis and pyroptosis with distinct disintegration of the cellular membrane. This causes release and presence of different intracellular cytotoxic, and tissue-damaging content as cell remnants in the extracellular environment. The apoptotic cells and apoptotic bodies get cleared with non-inflammatory outcomes, while lytic deaths associated remnants including histones and cell-free DNA cause pro-inflammatory responses. Indeed, the enhanced frequencies of neutrophil-associated proteases, cell-free DNA and autoantibodies in diverse pathologies including sepsis, asthma, lupus and rheumatoid arthritis, imply disturbed neutrophil resolution programmes in inflammatory and autoimmune diseases. Thus, the clearance mechanisms of neutrophils and associated remnants are vital for therapeutics. Though studies focused on clearance mechanisms of senescent or apoptotic neutrophils so far generated a good understanding of the same, clearance of neutrophils undergoing distinct lytic deaths, including NETs, are being the subjects of intense investigations. Here, in this review, we are providing the current updates in the clearance mechanisms of apoptotic neutrophils and focusing on not so well-defined recognition, uptake and degradation of neutrophils undergoing lytic death and associated remnants that may provide new therapeutic approaches in inflammation and autoimmunity.
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