Distinct roles of GPVI and integrin alpha(2)beta(1) 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 II, III 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.
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT. gavin.jarvis@pharmacology.oxford.ac.uk
Gavin E
GE
Jarvis
Ben T
BT
Atkinson
Daniel C
DC
Snell
Steve P
SP
Watson
D000244:Adenosine Diphosphate / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018955:CD36 Antigens / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D048429:Cell Size; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D025461:Feedback, Physiological; D006801:Humans; D066298:In Vitro Techniques; D038982:Integrin alpha2beta1 / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008854:Microscopy, Electron; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology*; D058919:Purinergic P2 Receptor Antagonists; D038981:Receptors, Collagen / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D038982:Integrin alpha2beta1; D008565:Membrane Proteins; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; C546383:P2ry1 protein, mouse; C548577:P2ry12 protein, mouse; D010980:Platelet Membrane Glycoproteins; D058919:Purinergic P2 Receptor Antagonists; D038981:Receptors, Collagen; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; C098341:platelet membrane glycoprotein VI; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen