Platelet-derived extracellular vesicles promote endothelial dysfunction in sepsis by enhancing neutrophil extracellular traps

BMC Immunology

Research

Xiuzhe Wang¹  Weidong Wu¹  Jifang Liang¹  Meini Jiang¹  Yanmei Xia¹ 

[1] Department of critical care medicine, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, 030032, Taiyuan, China;Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China;

关键词: Sepsis;    Endothelial dysfunction;    Platelet-derived extracellular vesicles (PEVs);    Neutrophil extracellular traps (NETs);   

DOI  :  10.1186/s12865-023-00560-5

 received in 2022-06-13, accepted in 2023-07-30,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe role of platelet-derived extracellular vesicles (PEVs) in the development of sepsis was investigated in this study.MethodsAfter collection of blood samples from sepsis patients and normal volunteers, the extracellular vesicles (EVs) were separated, followed by the isolation of PEVs from the blood of rats. Next, a sepsis rat model was constructed by cecal ligation and puncture (CLP), and rats received tail vein injection of PEVs to explore the role of PEVs in sepsis. Subsequently, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were adopted to determine the diameter of EVs and observe the morphology of PEVs, respectively; flow cytometry to detect the percentage of CD41-and CD61-positive EVs in isolated EVs; and ELISA to assess neutrophil extracellular trap (NET) formation, endothelial function injury-related markers in clinical samples or rat blood and serum inflammatory factor level.ResultsCompared with normal volunteers, the percentage of CD41- and CD61-positive EVs and the number of EVs were significantly elevated in sepsis patients. Moreover, sepsis patients also presented notably increased histone H3, myeloperoxidase (MPO), angiopoietin-2 and endocan levels in the blood, and such increase was positively correlated with the number of EVs. Also, animal experiments demonstrated that PEVs significantly promoted NET formation, mainly manifested as up-regulation of histone H3, high mobility group protein B1 (HMGB1), and MPO; promoted endothelial dysfunction (up-regulation of angiopoietin-2, endocan, and syndecan-1); and stimulated inflammatory response (up-regulation of interleukin (IL) -1β, IL-6, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP) -1) in the blood of sepsis rats.ConclusionPEVs aggravate endothelial function injury and inflammatory response in sepsis by promoting NET formation.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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