Bacteria-released outer membrane vesicles promote disseminated intravascular coagulation. Issue 178 (June 2019)

• Record Type: Journal Article
• Authors: Wang, Erhua; Liu, Yukun; Qiu, Xianhui; Tang, Yiting; Wang, Huadong; Xiao, Xianzhong; Chen, Fangping; Lu, Ben
• Is Part Of: Thrombosis research. Issue 178(2019)
• Page Start: 26
• Page End: 33
• Publication Date: 2019-06
• Subjects: DIC disseminated intravascular coagulation -- OMVs outer membrane vesicles -- PAI-1 plasminogen activator inhibitor type 1 -- TAT thrombin-antithrombin complex -- E.coli Escherichia coli -- TNF tumor necrosis factor -- LPS lipopolysaccharide -- LB Luria-Bertani broth -- LAL Limulus Amebocyte Lysate -- H&E stain hematoxylin and eosin stain -- ALT alanine transaminase -- AST aspartate aminotransferase -- CRE creatinine -- DAB 3, 3-diaminobenzidin -- TF tissue factor -- MPs microparticles -- PT prothrombin time -- APTT activated partial thromboplastin time -- TLR4 Toll-like receptor 4; Disseminated intravascular coagulation -- Sepsis -- Outer membrane vesicles -- Extracellular vesicles; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2019.03.019
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Sepsis is frequently complicated by disseminated intravascular coagulation (DIC), which promotes multiple organ dysfunctions and significantly increase the mortality of patients with sepsis. How bacteria cause DIC is not fully understood. Outer membrane vesicles (OMVs) are membrane-enclosed microvesicles released by variety of bacteria. The aim of this study is to determine whether OMVs contribute to the pathogenesis of DIC during bacterial infection. Methods: Wild-type (WT) or Toll-like receptor 4 (TLR4) knock-out mice were intraperitoneally injected with purified Escherichia coli ( E.coli ) derived OMVs, or with either wild type E.coli or E.coli with genetic deletion of ypjA, which is critical for OMV's production. Blood samples, liver and lung tissues were collected. The development of DIC was assessed in terms of the occurrence of coagulopathy, the thrombi deposition in livers and lungs, the multiple organ injuries, and the lethality. Results: Genetic deletion of ypjA significantly attenuated E.coli -induced coagulopathy, intravascular thrombi deposition, multiple organ injuries and mortality, whereas injection of purified E.coli -derived OMVs resulted in the development of DIC in a TLR4-dependent manner. Conclusions: OMVs importantly contribute to the pathogenesis of DIC during Gram-negative bacterial infection. These findings might open a new avenue to prevent infection-associated coagulopathy by targeting OMVs production. Highlights: Inhibition of OMVs formation attenuates E.coli -induced DIC. Injection of purified E.coli -derived OMVs could induce DIC. OMVs-induced DIC requires TLR4.