HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Platelet depletion in mice increases mortality after thermal injury

Platelets play a fundamental role in main-taining hemostasis and have been shown to participate in innate and adaptive immu-nity. However, the role of platelets in the immune response to injury remains unde-fined. We tested the importance of plate-lets in the host response to serious injury in a newly developed platelet-deficient mouse model. Wild-type and platelet-depleted C57BL/6J mice underwent a 25% full-thickness total body surface area ther-mal or sham injury. Platelet-deficient mice showed survival of 51 % at 48 hours after injury compared with 94 % to 100 % sur-vival in experimental control mice (P <.001). Necropsy and histology ruled out hemorrhage and hypovolemia as causes of death. Percentages of periph-eral blood monocytes (P <.01) and neu-trophils (P <.05) were increased be-tween 36 and 48 hours after thermal injury in platelet-deficient mice compared with control mice. Plasma levels of TNF (P <.001), IL-6 (P <.001), and MCP-1 (P <.05) were also elevated by 24 hours whereas levels of TGF1 were reduced between 24 and 36 hours following injury in platelet-depleted mice (P <.001) com-pared with control mice. Our findings demonstrate for the first time that plate-lets play a critical protective role during the host response to injury. Moreover, our findings suggest that platelets and, more importantly, platelet-derived TGF1 modu-late the systemic inflammatory response occurring after injury. (Blood. 2006;107