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

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

  • Nat Commun. 2022 Aug 6;13(1):4583. doi: 10.1038/s41467-022-32325-w.
Wenjie Bao  # 1,  Huayue Xing  # 1,  Shiwei Cao 2,  Xin Long 3,  Haifeng Liu 1,  Junwei Ma 1,  Fan Guo 3 4,  Zimu Deng 5,  Xiaolong Liu 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320, Yueyang Road, Shanghai, China.
  • 2 School of Life Science and Technology, Shanghai Tech University, Shanghai, 200031, China.
  • 3 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 4 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
  • 5 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320, Yueyang Road, Shanghai, China. dengzimu@sibcb.ac.cn.
  • 6 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320, Yueyang Road, Shanghai, China. liux@sibcb.ac.cn.
  • 7 School of Life Science and Technology, Shanghai Tech University, Shanghai, 200031, China. liux@sibcb.ac.cn.
  • 8 Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China. liux@sibcb.ac.cn.
  • # Contributed equally.
PMID: 35933512 DOI: 10.1038/s41467-022-32325-w
Abstract

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.

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