Xiang's Research Shows that Platelets Inhibit Inflammation to Protect from Septic Shock

Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway. Xiang B, Zhang G, Guo L, Li XA, Morris AJ, Daugherty A, Whiteheart SW, Smyth SS, Li Z. Nat Commun. 2013;4:2657. doi: 10.1038/ncomms3657. PMID: 24150174

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 Ibα 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-α 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/PGE₂/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.