Distinct roles of GPVI and integrin α2β1 in platelet shape change and aggregation induced by different collagens

1 Various platelet membrane glycoproteins have been proposed as receptors for collagen, in some cases as receptors For specific collagen types. In this study we have compared the ability of a range of collagen types to activate platelets. 2 Bovine collagen types I-V, native equine tendon collagen fibrils and collagen-related peptide (CRP) all induced platelet aggregation and shape change. 3 Responses were abolished in FcRgamma chain-deficient platelets, which also lack GPVI, indicating a critical dependence on the GPVI/FcRgamma chain complex. 4 Responses to all collagens were unaffected in CD36-deficient platelets. 5 A monoclonal antibody (6F1) which binds to the alpha(2) integrin subunit of human platelets had a minimal effect on the rate and extent of aggregation induced by the collagens; however, it delayed the onset of aggregation following addition of all collagens. For shape change, 6F1 abolished the response induced by collagen types I and IV, substantially attenuated that to collagen types 11, 111 and V, but only partially inhibited Horm collagen. 6 Simultaneous blockade of the P2Y(1) and P2Y(12) receptors, and inhibition of cyclo-oxygenase demonstrated that CRP can activate platelets independently of ADP and TxA(2); however, responses to the collagens were dependent on these mediators. 7 This study confirms the importance of the GPVI/FcRgamma chain complex in platelet responses induced by a range of collagen agonists, while providing no evidence for collagen type-specific receptors. It also provides evidence for a modulatory role Of alpha(2)beta(1), the significance of which depends on the collagen preparation.