title: Platelets, complement, and contact activation: partners in inflammation and thrombosis.
abstract: Platelet activation during thrombotic events is closely associated with complement and contact system activation, which in turn leads to inflammation. Here we review the interactions between activated platelets and the complement and contact activation systems in clotting blood. Chondroitin sulfate A (CS-A), released from alpha granules during platelet activation, is a potent mediator of crosstalk between 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 . 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 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 is induced by material surfaces. Thus, in addition to their traditional role as initiators of secondary hemostasis, platelets also act as mediators and regulators of inflammation in thrombotic events.
authors.affiliation: Dept of Immunology, Genetics and Pathology, Rudbeck Laboratory C5:3, Uppsala University, SE-751 85 Uppsala, Sweden. osama.hamad@igp.uu.se
authors.forename: Osama A
authors.initials: OA
authors.lastname: Hamad
authors.forename: Jennie
authors.initials: J
authors.lastname: Bäck
authors.forename: Per H
authors.initials: PH
authors.lastname: Nilsson
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
mesh_terms: D001792:Blood Platelets / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015539:Platelet Activation / Q000276:immunology*; D013927:Thrombosis / Q000276:immunology*
chemical_list: D003165:Complement System Proteins