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

Binggang Xiang, Guoying Zhang, Ling Guo, Xiang-An Li, Andrew J. Morris, Alan Daugherty, Sidney W. Whiteheart, Susan S. Smyth and Zhenyu Li ()
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Binggang Xiang: Saha Cardiovascular Center, University of Kentucky
Guoying Zhang: Saha Cardiovascular Center, University of Kentucky
Ling Guo: University of Kentucky
Xiang-An Li: Saha Cardiovascular Center, University of Kentucky
Andrew J. Morris: Saha Cardiovascular Center, University of Kentucky
Alan Daugherty: Saha Cardiovascular Center, University of Kentucky
Sidney W. Whiteheart: University of Kentucky
Susan S. Smyth: Saha Cardiovascular Center, University of Kentucky
Zhenyu Li: Saha Cardiovascular Center, University of Kentucky

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3657

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