Current Topics in Innate Immunity II

Osama A. Hamad, Jennie Bäck, Per H. Nilsson, Bo Nilsson, Kristina N. Ekdahl

John D. Lambris, George Hajishengallis

Platelet activation during thrombotic events is closely associated with complement and contact system activation, which in turn leads to inflammation inflammation . Here we review the interactions between activated platelets platelets and the complement and contact activation contact activation systems in clotting blood. Chondroitin sulfate Chondroitin sulfate Chondroitin sulfate A (CS-A), released from alpha granules during platelet activation, is a potent mediator of crosstalk between platelets platelets and the complement system. CS-A activates complement in the fluid phase, generating anaphylatoxins that mediate leukocyte activation. No complement activation seems to occur on the activated platelet surface, but C3 in the form of C3(H(2)O) is bound to the surfaces of activated platelets platelets . This finding is consistent with the strong expression of membrane-bound complement regulators present at the platelet surface. CS-A exposed on the activated platelets platelets is to a certain amount responsible for recruiting soluble regulators to the surface. Platelet-bound C3(H(2)O) acts as a ligand for leukocyte CR1 (CD35), potentially enabling platelet-leukocyte interactions. In addition, platelet activation leads to the activation of contact system enzymes, which are specifically inhibited by antithrombin, rather than by C1INH, as is the case when contact activation contact activation is induced by material surfaces. Thus, in addition to their traditional role as initiators of secondary hemostasis, platelets platelets also act as mediators and regulators of inflammation inflammation in thrombotic events.