Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury

Jörn Karhausen, Hae Woong Choi, Krishna Rao Maddipati, Joseph P. Mathew, Qing Ma, Yacine Boulaftali, Robert Hugh Lee, Wolfgang Bergmeier, Soman N. Abraham

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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.

Original languageEnglish
Article numbereaay6314
JournalScience Advances
Issue number12
Publication statusPublished - 2020

Bibliographical note

Funding Information:
This work was funded by U.S. National Institutes of Health grants 1R56HL126891-01 to J.K.; 1R35 HL144976-01 to W.B.; R01-AI096305, R56-DK095198, and U01-AI082107 to S.N.A.; T32HL007149 to R.H.L.; and 1R01HL130443 to J.K. and J.P.M. Further support came from National Center for Research Resources, National Institutes of Health grant S10RR027926 to K.R.M., the American Heart Association grant 15SDG25080046 to J.K., and a Duke Clinical and Translational Science Institute grant (UL1TR002553) to J.K.

Publisher 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).

ASJC Scopus subject areas

  • General


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