Small Extracellular Vesicles Propagate the Inflammatory Response After Trauma.
Acute Kidney Injury
/ etiology
Animals
Disease Models, Animal
Endothelial Cells
/ immunology
Extracellular Vesicles
/ immunology
Inflammation
/ immunology
Male
Mice
Mice, Inbred C57BL
Multiple Trauma
/ complications
Neutrophil Infiltration
/ physiology
Respiratory Distress Syndrome
/ etiology
Sepsis
/ etiology
endothelium
inflammation
neutrophils
small extracellular vesicles
trauma
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
20
08
2021
received:
07
06
2021
pubmed:
30
10
2021
medline:
17
3
2022
entrez:
29
10
2021
Statut:
ppublish
Résumé
Trauma is the leading cause of death in individuals under 44 years of age. Thorax trauma (TxT) is strongly associated with trauma-related death, an unbalanced innate immune response, sepsis, acute respiratory distress syndrome, and multiple organ dysfunction. It is shown that different in vivo traumata, such as TxT or an in vitro polytrauma cytokine cocktail trigger secretion of small extracellular nanovesicles (sEVs) from endothelial cells with pro-inflammatory cargo. These sEVs transfer transcripts for ICAM-1, VCAM-1, E-selectin, and cytokines to systemically activate the endothelium, facilitate neutrophil-endothelium interactions, and destabilize barrier integrity. Inhibition of sEV-release after TxT in mice ameliorates local as well as systemic inflammation, neutrophil infiltration, and distant organ damage in kidneys (acute kidney injury, AKI). Vice versa, injection of TxT-plasma-sEVs into healthy animals is sufficient to trigger pulmonary and systemic inflammation as well as AKI. Accordingly, increased sEV concentrations and transfer of similar cargos are observed in polytrauma patients, suggesting a fundamental pathophysiological mechanism.
Identifiants
pubmed: 34713625
doi: 10.1002/advs.202102381
pmc: PMC8693079
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2102381Subventions
Organisme : Ulm University
Organisme : DFG
ID : 251293561
Organisme : DFG
ID : 376202546
Organisme : DFG
ID : 380319649
Informations de copyright
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
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