近日，中南大学湘雅三医院吕奔课题组发现，细菌内毒素通过Gasdermin D依赖的磷脂酰丝氨酸暴露激活凝血级联。 该研究于2019年12月10日在线发表于国际一流学术期刊《免疫》。

研究人员检查了脂多糖（LPS）激活凝血的基础机制，LPS是革兰氏阴性细菌的主要细胞壁成分。研究人员发现，胞浆LPS受体caspase-11激活了凝血级联反应。caspase-11以与细胞死亡无关的方式，通过触发GSDMD（gasdermin D）孔的形成和随后的磷脂酰丝氨酸的暴露，增强了凝血的起始因子组织因子（TF）的活化。GSDMD孔介导了钙内流，从而通过跨膜蛋白16F（一种钙依赖性磷脂稀疏酶）诱导了磷脂酰丝氨酸的暴露。Casp11的敲除、Gsdmd的减少、磷脂酰丝氨酸或TF的中和阻止了LPS诱导的弥散性血管内凝血（DIC）。在败血病患者中，血清白介素（IL）-1α和IL-1β（GSSDD活化的生物标志物）的浓度与外周血白细胞中磷脂酰丝氨酸的暴露和DIC评分相关。这些发现将LPS的免疫识别与凝结机制联系起来，对DIC的治疗有一定影响。

据了解，凝血系统的过度激活导致危及生命的DIC。

附：英文原文

Title: Bacterial Endotoxin Activates the Coagulation Cascade through Gasdermin D-Dependent Phosphatidylserine Exposure

Author: Xinyu Yang, Xiaoye Cheng, Yiting Tang, Xianhui Qiu, Yupeng Wang, Haixia Kang, Jianfeng Wu, Zhongtai Wang, Yukun Liu, Fangping Chen, Xianzhong Xiao, Nigel Mackman, Timothy R. Billiar, Jiahuai Han, Ben Lu

Issue&Volume: December 10, 2019

Abstract: Excessive activation of the coagulation system leads to life-threatening disseminatedintravascular coagulation (DIC). Here, we examined the mechanisms underlying the activationof coagulation by lipopolysaccharide (LPS), the major cell-wall component of Gram-negativebacteria. We found that caspase-11, a cytosolic LPS receptor, activated the coagulationcascade. Caspase-11 enhanced the activation of tissue factor (TF), an initiator ofcoagulation, through triggering the formation of gasdermin D (GSDMD) pores and subsequentphosphatidylserine exposure, in a manner independent of cell death. GSDMD pores mediatedcalcium influx, which induced phosphatidylserine exposure through transmembrane protein16F, a calcium-dependent phospholipid scramblase. Deletion of Casp11, ablation of Gsdmd, or neutralization of phosphatidylserine or TF prevented LPS-induced DIC. In septicpatients, plasma concentrations of interleukin (IL)-1α and IL-1β, biomarkers of GSDMDactivation, correlated with phosphatidylserine exposure in peripheral leukocytes andDIC scores. Our findings mechanistically link immune recognition of LPS to coagulation,with implications for the treatment of DIC.

DOI: 10.1016/j.immuni.2019.11.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30463-7