Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway.

ABSTRACT: Although it has long been known that patients with sepsis often have thrombocytopenia and that septic patients with severe thrombocytopenia have a poor prognosis and higher mortality, the role of platelets in the pathogenesis of sepsis is poorly understood. Here we report a protective role of platelets in septic shock. We show that experimental thrombocytopenia induced by intraperitoneal injection of an anti-glycoprotein Ib? monoclonal antibody increases mortality and aggravates organ failure, whereas transfusion of platelets reduces mortality in lipopolysaccharide-induced endotoxemia and a bacterial infusion mouse sepsis model. Plasma concentrations of proinflammatory cytokines TNF-? and IL-6 are elevated by thrombocytopenia and decreased by platelet transfusion in septic mice. Furthermore, we identify that platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the COX1/PGE?/EP4-dependent pathway. Thus, these findings demonstrate a previously unappreciated role for platelets in septic shock and suggest that platelet transfusion may be effective in treating severely septic patients.

SUBMITTER: Xiang B 

PROVIDER: S-EPMC4217311 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature