Platelet P2Y Receptor Deletion or Pharmacological Inhibition does not Protect Mice from Sepsis or Septic Shock.

Fiche publication

Date publication

juillet 2021

Journal

TH open : companion journal to thrombosis and haemostasis

Auteurs

Membres identifiés du Cancéropôle Est :
Dr GACHET Christian

Tous les auteurs :
Rabouel Y, Magnenat S, Delabranche X, Gachet C, Hechler B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/34447900

Résumé

Platelets are increasingly appreciated as key effectors during sepsis, raising the question of the usefulness of antiplatelet drugs to treat patients with sepsis. Evaluate the potential contribution of the platelet P2Y receptor in the pathogenesis of polymicrobial-induced sepsis and septic shock in mice. The effects of P2Y inhibition using clopidogrel treatment and of platelet-specific deletion of the P2Y receptor in mice were examined in two severity grades of cecal ligation and puncture (CLP) leading to mild sepsis or septic shock. Twenty hours after induction of the high grade CLP, clopidogrel- and vehicle-treated mice displayed a similar 30% decrease in mean arterial blood pressure (MAP) characteristic of shock. Septic shock-induced thrombocytopenia was not modified by clopidogrel treatment. Plasma concentrations of inflammatory cytokines and myeloperoxidase (MPO) were similarly increased in clopidogrel- and vehicle-treated mice, indicating comparable increase in systemic inflammation. Thrombin-antithrombin (TAT) complexes and the extent of organ damage were also similar. In mild-grade CLP, clopidogrel- and vehicle-treated mice did not display a significant decrease in MAP, while thrombocytopenia and plasma concentrations of TNFα, IL6, IL10, MPO, TAT and organ damage reached similar levels in both groups, although lower than those reached in the high grade CLP. Similarly, mice with platelet-specific deletion of the P2Y receptor were not protected from CLP-induced sepsis or septic shock. The platelet P2Y receptor does not contribute to the pathogenesis of sepsis or septic shock in mice, suggesting that P2Y receptor antagonists may not be beneficial in patients with sepsis or septic shock.