HMGB1-Mediated Neutrophil Extracellular Trap Formation Exacerbates Intestinal Ischemia/Reperfusion-Induced Acute Lung Injury
HMGB1-Mediated Neutrophil Extracellular Trap Formation Exacerbates Intestinal Ischemia/Reperfusion-Induced Acute Lung Injury
复制标题
HMGB1 介导的中性粒细胞胞外陷阱形成加剧肠缺血/再灌注引起的急性肺损伤
DOI：
10.4049/jimmunol.2100593
复制
发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Wen ShiHong
中科院分区：
文献类型：
--
作者：
Zhan YaQing;Ling YiHong;Deng QiWen;Qiu YuXin;Shen JianTong;Lai HanJin;Chen ZhaoRong;Huang ChanYan;Liang LiQun;Li Xiang;Wu JianFeng;Huang WenQi;Wen ShiHong
要点：活化的中性粒细胞流入和中性粒细胞胞外诱捕网（NETosis）形成促成肠缺血再灌注（I/R）诱导的急性肺损伤（ALI）。针对NETosis和高迁移率族蛋白B1（HMGB1）信号传导进行干预可有效减轻肠I/R诱导的ALI。活化的中性粒细胞流入肺部是组织病理学特征。
Key Points Activated neutrophil influx and NETosis contribute to intestinal I/R-induced ALI. Targeting NETosis and HMGB1 signaling effectively reduces intestinal I/R-induced ALI. Influx of activated neutrophils into the lungs is the histopathologic hallmark of acute lung injury (ALI) after intestinal ischemia/reperfusion (I/R). Neutrophils can release DNA and granular proteins to form cytotoxic neutrophil extracellular traps (NETs), which promotes bystander tissue injury. However, whether NETs are responsible for the remote ALI after intestinal I/R and the mechanisms underlying the dissemination of harmful gut-derived mediators to the lungs are unknown. In the C57BL/6J mouse intestinal I/R model, DNase I–mediated degradation and protein arginine deiminase 4 (PAD4) inhibitor–mediated inhibition of NET treatments reduced NET formation, tissue inflammation, and pathological injury in the lung. High-mobility group protein B1 (HMGB1) blocking prevented NET formation and protected against tissue inflammation, as well as reduced cell apoptosis and improved survival rate. Moreover, recombinant human HMGB1 administration further drives NETs and concurrent tissue toxic injury, which in turn can be reversed by neutrophil deletion via anti-Ly6G Ab i.p. injection. Furthermore, global MyD88 deficiency regulated NET formation and alleviated the development of ALI induced by intestinal I/R. Thus, HMGB1 released from necroptotic enterocytes caused ALI after intestinal I/R by inducing NET formation. Targeting NETosis and the HMGB1 pathway might extend effective therapeutic strategies to minimize intestinal I/R-induced ALI.
登录
查看更多内容
影响因子：
5
作者：
Liang Y;Pan B;Alam HB;Deng Q;Wang Y;Chen E;Liu B;Tian Y;Williams AM;Duan X;Wang Y;Zhang J;Li Y
通讯作者：
Li Y
细胞外组蛋白是败血症死亡的主要介体。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.3
作者：
通讯作者：
--
影响因子：
29.4
作者：
Merza, Mohammed;Hartman, Hannes;Thorlacius, Henrik
通讯作者：
Thorlacius, Henrik
影响因子：
19.6
作者：
Doi, Kent;Ishizu, Tomoko;Noiri, Eisei
通讯作者：
Noiri, Eisei