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

Publication ,  Journal Article
Karhausen, J; Choi, HW; Maddipati, KR; Mathew, JP; Ma, Q; Boulaftali, Y; Lee, RH; Bergmeier, W; Abraham, SN
Published in: Sci Adv
March 2020

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.

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Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

March 2020

Volume

6

Issue

12

Start / End Page

eaay6314

Location

United States

Related Subject Headings

  • Rats
  • Platelet Activation
  • Platelet Activating Factor
  • Organ Specificity
  • Mast Cells
  • Inflammation
  • Disease Susceptibility
  • Cell Degranulation
  • Blood Platelets
  • Animals
 

Citation

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Karhausen, J., Choi, H. W., Maddipati, K. R., Mathew, J. P., Ma, Q., Boulaftali, Y., … Abraham, S. N. (2020). Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury. Sci Adv, 6(12), eaay6314. https://doi.org/10.1126/sciadv.aay6314
Karhausen, Jörn, Hae Woong Choi, Krishna Rao Maddipati, Joseph P. Mathew, Qing Ma, Yacine Boulaftali, Robert Hugh Lee, Wolfgang Bergmeier, and Soman N. Abraham. “Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury.Sci Adv 6, no. 12 (March 2020): eaay6314. https://doi.org/10.1126/sciadv.aay6314.
Karhausen J, Choi HW, Maddipati KR, Mathew JP, Ma Q, Boulaftali Y, et al. Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury. Sci Adv. 2020 Mar;6(12):eaay6314.
Karhausen, Jörn, et al. “Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury.Sci Adv, vol. 6, no. 12, Mar. 2020, p. eaay6314. Pubmed, doi:10.1126/sciadv.aay6314.
Karhausen J, Choi HW, Maddipati KR, Mathew JP, Ma Q, Boulaftali Y, Lee RH, Bergmeier W, Abraham SN. Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury. Sci Adv. 2020 Mar;6(12):eaay6314.

Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

March 2020

Volume

6

Issue

12

Start / End Page

eaay6314

Location

United States

Related Subject Headings

  • Rats
  • Platelet Activation
  • Platelet Activating Factor
  • Organ Specificity
  • Mast Cells
  • Inflammation
  • Disease Susceptibility
  • Cell Degranulation
  • Blood Platelets
  • Animals