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, Zhenyu Li

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

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/PGE 2 /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.

Original languageEnglish
Article number2657
JournalNature Communications
Volume4
DOIs
StatePublished - Oct 23 2013

Bibliographical note

Funding Information:
This work was supported by the American Heart Association Midwest Affiliate Grant-in-Aid 0855698G (to Z.L.) and in part supported by the American Society of Hematology (ASH) bridge Grant Award and the NIH/National Center for Research Resources Centers of Biomedical Research Excellence in Obesity and Cardiovascular Disease Grant P20 RR021954. B.X. is a recipient of the American Heart Association Postdoctoral Fellowship Award. This work was support in part by resources provided by the Lexington VA Medical Center. We thank Dr. Richard Charnigo for his assistance with statistical analysis and Dr. Wendy S. Katz for her technical support for the histologic analysis. We thank Dr. Prabhakara R. Nagareddy and Judy F. Glass for their assistance with detection of monocyte depletion by flow cytometry.

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Physics and Astronomy (all)

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