Neutrophils restrain sepsis associated coagulopathy via extracellular vesicles carrying superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis

Disseminated intravascular coagulation (DIC) is a complication of sepsis currently lacking effective therapeutic options. Excessive inflammatory responses are emerging triggers of coagulopathy during sepsis, but the interplay between the immune system and coagulation are not fully understood. Here w...

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Vydáno v:Nature communications Ročník 13; číslo 1; s. 4583 - 16
Hlavní autoři: Bao, Wenjie, Xing, Huayue, Cao, Shiwei, Long, Xin, Liu, Haifeng, Ma, Junwei, Guo, Fan, Deng, Zimu, Liu, Xiaolong
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 06.08.2022
Nature Publishing Group
Nature Portfolio
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Accumulation
Animal models
Animals
Antioxidants
Blood Coagulation Disorders
Coagulation
Disease Models, Animal
Disseminated intravascular coagulation
Disseminated Intravascular Coagulation - etiology
Endothelium
Extracellular Vesicles
Humanities and Social Sciences
Immune system
Inflammation
Leukocytes (neutrophilic)
Lipopolysaccharides
Lipopolysaccharides - toxicity
Mice
Mitochondria
multidisciplinary
Neutrophils
Oxidation
Oxygen
Reactive Oxygen Species
Science
Science (multidisciplinary)
Sepsis
Sepsis - complications
Superoxide dismutase
Superoxide Dismutase - metabolism
Vesicles
ISSN:2041-1723, 2041-1723
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Shrnutí:Disseminated intravascular coagulation (DIC) is a complication of sepsis currently lacking effective therapeutic options. Excessive inflammatory responses are emerging triggers of coagulopathy during sepsis, but the interplay between the immune system and coagulation are not fully understood. Here we utilize a murine model of intraperitoneal lipopolysaccharide stimulation and show neutrophils in the circulation mitigate the occurrence of DIC, preventing subsequent septic death. We show circulating neutrophils release extracellular vesicles containing mitochondria, which contain superoxide dismutase 2 upon exposure to lipopolysaccharide. Extracellular superoxide dismutase 2 is necessary to induce neutrophils’ antithrombotic function by preventing endothelial reactive oxygen species accumulation and alleviating endothelial dysfunction. Intervening endothelial reactive oxygen species accumulation by antioxidants significantly ameliorates disseminated intravascular coagulation improving survival in this murine model of lipopolysaccharide challenge. These findings reveal an interaction between neutrophils and vascular endothelium which critically regulate coagulation in a model of sepsis and may have potential implications for the management of disseminated intravascular coagulation. Disseminated intravascular coagulation is associated with sepsis and a number of inflammatory components have been linked to sepsis associated coagulopathy. Here the authors show neutrophils can prevent lethal coagulopathy via the production of extracellular vesicles that carry superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-32325-w