炎症
巨噬细胞
吞噬作用
小胶质细胞
先天免疫系统
免疫系统
中性粒细胞胞外陷阱
瓜氨酸化
细胞生物学
免疫学
生物
瓜氨酸
体外
生物化学
精氨酸
氨基酸
作者
Shenwei Gao,Kua Zheng,Jiafei Lou,Yinfang Wu,Fangyi Yu,Qingyu Weng,Yanping Wu,Miao Li,Chen Zhu,Zhongnan Qin,Ruixin Jia,Songmin Ying,Huahao Shen,Zhihua Chen,Wen Li
标识
DOI:10.1016/j.ajpath.2024.05.008
摘要
Accumulating evidence has substantiated the potential of ambient particulate matter (PM) to elicit detrimental health consequences in the respiratory system, notably airway inflammation. Macrophages, a pivotal component of the innate immune system, assume a crucial function in responding to exogenous agents. However, the roles and detailed mechanisms in regulating PM-induced airway inflammation remain unclear. The current study revealed that PM had the ability to stimulate the formation of macrophage extracellular traps (METs) both in vitro and in vivo. This effect was dependent on peptidylarginine deiminase type 4 (PAD4)-mediated histone citrullination. Additionally, reactive oxygen species were involved in the formation of PM-induced METs, in parallel with PAD4. Genetic deletion of PAD4 in macrophages resulted in an up-regulation of inflammatory cytokine expression. Moreover, mice with PAD4-specific knockout in myeloid cells exhibited exacerbated PM-induced airway inflammation. Mechanistically, inhibition of METs suppressed the phagocytic ability in macrophages, leading to airway epithelial injuries and an aggravated PM-induced airway inflammation. The present study demonstrates that METs play a crucial role in promoting the phagocytosis and clearance of PM by macrophages, thereby suppressing airway inflammation. Furthermore, it suggests that activation of METs may represent a novel therapeutic strategy for PM-related airway disorders.
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