Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
04
07
2019
accepted:
20
12
2019
entrez:
25
3
2020
pubmed:
25
3
2020
medline:
25
11
2020
Statut:
epublish
Résumé
Platelet responses have been associated with end-organ injury and mortality following complex insults such as cardiac surgery, but how platelets contribute to these pathologies remains unclear. Our studies originated from the observation of microvascular platelet retention in a rat cardiac surgery model. Ensuing work supported the proximity of platelet aggregates with perivascular mast cells (MCs) and demonstrated that platelet activation triggered systemic MC activation. We then identified platelet activating factor (PAF) as the platelet-derived mediator stimulating MCs and, using chimeric animals with platelets defective in PAF generation or MCs lacking PAF receptor, defined the role of this platelet-MC interaction for vascular leakage, shock, and tissue inflammation. In application of these findings, we demonstrated that inhibition of platelet activation in modeled cardiac surgery blunted MC-dependent inflammation and tissue injury. Together, our work identifies a previously undefined mechanism of inflammatory augmentation, in which platelets trigger local and systemic responses through activation of perivascular MCs.
Identifiants
pubmed: 32206714
doi: 10.1126/sciadv.aay6314
pii: aay6314
pmc: PMC7080499
doi:
Substances chimiques
Platelet Activating Factor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaay6314Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL130443
Pays : United States
Organisme : NHLBI NIH HHS
ID : R56 HL126891
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL144976
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI082107
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI096305
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027926
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007149
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002553
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK095198
Pays : United States
Organisme : NIDDK NIH HHS
ID : K12 DK100024
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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