中性粒细胞胞外陷阱
肺
胞浆
线粒体
再灌注损伤
细胞外
生物
缺血
发病机制
细胞生物学
体内
炎症
药理学
免疫学
医学
生物化学
酶
内科学
生物技术
作者
Chen Zhao,Fangrong Liang,Mengling Ye,Siyi Wu,Yi Qin,Lu Zhao,Lu Zhang,Jingni He,Liming Cen,Fei Lin
标识
DOI:10.1038/s41420-023-01663-z
摘要
Abstract Lung ischemia/reperfusion injury (LIRI) is a complex pathophysiological process, with the histopathological hallmark of neutrophils migrating into the lungs. Neutrophil extracellular traps (NETs) have been suggested to exert a critical role in the pathogenesis of inflammation and infection in humans and animals, while the exact functions and underlying mechanisms of NETs in LIRI remain insufficiently elucidated. In this study, we investigated the role of pore-forming protein gasdermin D (GSDMD) on NETs release in LIRI induced by lung ischemia/reperfusion (I/R). We found that disulfiram, a GSDMD inhibitor, dramatically reduced NETs release and pathological injury in lung I/R in vivo and in vitro. Additionally, GSDMD caused mitochondrial DNA (mtDNA) leaking into the neutrophil cytosol, and then the cytoplasmic mtDNA activated the cGAS-STING signaling pathway and stimulated NETs formation in lung I/R. Furthermore, inhibition of cGAS/STING pathway could inhibit cytosol mtDNA mediated NETs formation.
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