Platelets express CD40 ligand (CD40L) and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanism. CD40L-mediated platelet activation requires the family of TNF receptor-associated factor 2 (TRAF2). Here we show that platelet also express TRAF3, which plays a negative role in regulating platelet activation. Thrombin- or collagen-induced platelet aggregation and secretion are increased in TRAF3 knockout mice. The expression of integrin IIb3, GPVI, and PAR4 was similar between TRAF3 knockout platelets and wild type controls, suggesting that increased platelet activation in the TRAF3 knockout mice is not due to increased expression of platelet receptors. TRAF2 expression was not affect by deletion of TRAF3 eitehr. Using the FeCl 3 -induced arterial thrombosis model, we found that time to formation of thrombi in was significantly shortened in TRAF3 knockout mice. Thus, TRAF3 plays a negative role in platelet activation and in thrombus formation in vivo.
