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Critical Care
Published in: Critical Care 1/2020

01-12-2020 | Septicemia | Research

Platelet-derived exosomes promote neutrophil extracellular trap formation during septic shock

Authors: Yang Jiao, Weiwei Li, Wei Wang, Xingyu Tong, Ran Xia, Jie Fan, Jianer Du, Chengmi Zhang, Xueyin Shi

Published in: Critical Care | Issue 1/2020

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Abstract

Background

Platelets have been demonstrated to be potent activators of neutrophil extracellular trap (NET) formation during sepsis. However, the mediators and molecular pathways involved in human platelet-mediated NET generation remain poorly defined. Circulating plasma exosomes mostly originating from platelets may induce vascular apoptosis and myocardial dysfunction during sepsis; however, their role in NET formation remains unclear. This study aimed to detect whether platelet-derived exosomes could promote NET formation during septic shock and determine the potential mechanisms involved.

Methods

Polymorphonuclear neutrophils (PMNs) were cocultured with exosomes isolated from the plasma of healthy controls and septic shock patients or the supernatant of human platelets stimulated ex vivo with phosphate buffer saline (PBS) or lipopolysaccharide (LPS). A lethal cecal ligation and puncture (CLP) mouse model was used to mimic sepsis in vivo; then, NET formation and molecular pathways were detected.

Results

NET components (dsDNA and MPO-DNA complexes) were significantly increased in response to treatment with septic shock patient-derived exosomes and correlated positively with disease severity and outcome. In the animal CLP model, platelet depletion reduced plasma exosome concentration, NET formation, and lung injury. Mechanistic studies demonstrated that exosomal high-mobility group protein 1 (HMGB1) and/or miR-15b-5p and miR-378a-3p induced NET formation through the Akt/mTOR autophagy pathway. Furthermore, the results suggested that IκB kinase (IKK) controls platelet-derived exosome secretion in septic shock.

Conclusions

Platelet-derived exosomes promote excessive NET formation in sepsis and subsequent organ injury. This finding suggests a previously unidentified role of platelet-derived exosomes in sepsis and may lead to new therapeutic approaches.
Appendix
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Metadata
Title
Platelet-derived exosomes promote neutrophil extracellular trap formation during septic shock
Authors
Yang Jiao
Weiwei Li
Wei Wang
Xingyu Tong
Ran Xia
Jie Fan
Jianer Du
Chengmi Zhang
Xueyin Shi
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-03082-3

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