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Elsevier Science

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. 2019 Dec 17;51(6):983-996.e6.

doi: 10.1016/j.immuni.2019.11.005. Epub 2019 Dec 10.

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

Xinyu Yang¹, Xiaoye Cheng¹, Yiting Tang², Xianhui Qiu¹, Yupeng Wang³, Haixia Kang⁴, Jianfeng Wu⁵, Zhongtai Wang¹, Yukun Liu¹, Fangping Chen¹, Xianzhong Xiao⁶, Nigel Mackman⁷, Timothy R Billiar⁸, Jiahuai Han⁵, Ben Lu⁹

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¹ Department of Hematology and Critical Care Medicine, The 3rd Xiangya Hospital, Central South University, Changsha 410000, P.R. China.
² Department of Physiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province 410000, P.R. China.
³ National Institute of Biological Sciences, Beijing, 102206 Beijing, China.
⁴ Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai 200025, P.R. China.
⁵ State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
⁶ Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province 410000, P.R. China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan Province 410000, P.R. China.
⁷ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁸ Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
⁹ Department of Hematology and Critical Care Medicine, The 3rd Xiangya Hospital, Central South University, Changsha 410000, P.R. China; Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province 410000, P.R. China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan Province 410000, P.R. China. Electronic address: xybenlu@qiuluzeuv.cn.

PMID: 31836429
DOI: 10.1016/j.immuni.2019.11.005

Free article

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

Xinyu Yang et al. Immunity. 2019.

Free article

. 2019 Dec 17;51(6):983-996.e6.

doi: 10.1016/j.immuni.2019.11.005. Epub 2019 Dec 10.

"VSports" Authors

Xinyu Yang¹, Xiaoye Cheng¹, Yiting Tang², Xianhui Qiu¹, Yupeng Wang³, Haixia Kang⁴, Jianfeng Wu⁵, Zhongtai Wang¹, Yukun Liu¹, Fangping Chen¹, Xianzhong Xiao⁶, Nigel Mackman⁷, Timothy R Billiar⁸, Jiahuai Han⁵, Ben Lu⁹

Affiliations

¹ Department of Hematology and Critical Care Medicine, The 3rd Xiangya Hospital, Central South University, Changsha 410000, P.R. China.
² Department of Physiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province 410000, P.R. China.
³ National Institute of Biological Sciences, Beijing, 102206 Beijing, China.
⁴ Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai 200025, P.R. China.
⁵ State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
⁶ Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province 410000, P.R. China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan Province 410000, P.R. China.
⁷ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁸ Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
⁹ Department of Hematology and Critical Care Medicine, The 3rd Xiangya Hospital, Central South University, Changsha 410000, P.R. China; Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province 410000, P.R. China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan Province 410000, P.R. China. Electronic address: xybenlu@qiuluzeuv.cn.

PMID: 31836429
DOI: 10.1016/j.immuni.2019.11.005

Abstract

Excessive activation of the coagulation system leads to life-threatening disseminated intravascular coagulation (DIC). Here, we examined the mechanisms underlying the activation of coagulation by lipopolysaccharide (LPS), the major cell-wall component of Gram-negative bacteria. We found that caspase-11, a cytosolic LPS receptor, activated the coagulation cascade. Caspase-11 enhanced the activation of tissue factor (TF), an initiator of coagulation, through triggering the formation of gasdermin D (GSDMD) pores and subsequent phosphatidylserine exposure, in a manner independent of cell death. GSDMD pores mediated calcium influx, which induced phosphatidylserine exposure through transmembrane protein 16F, a calcium-dependent phospholipid scramblase. Deletion of Casp11, ablation of Gsdmd, or neutralization of phosphatidylserine or TF prevented LPS-induced DIC VSports手机版. In septic patients, plasma concentrations of interleukin (IL)-1α and IL-1β, biomarkers of GSDMD activation, correlated with phosphatidylserine exposure in peripheral leukocytes and DIC scores. Our findings mechanistically link immune recognition of LPS to coagulation, with implications for the treatment of DIC. .

Keywords: caspase-11; coagulation; non-canonical inflammasome; phosphatidylserine exposure; sepsis. V体育安卓版.

Copyright © 2019 Elsevier Inc. All rights reserved. V体育ios版.

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