Adhesion of human and mouse platelets to collagen under shear: a unifying model
- 9 March 2005
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 19 (7), 1-22
- https://doi.org/10.1096/fj.04-1940fje
Abstract
There is presently confusion as to the roles of alpha2beta1 and GPVI in supporting platelet adhesion and aggregate formation on collagen at intermediate/high shear. Recent studies have reported essential, partial, or dispensable roles for either receptor in supporting these events, and the possibility that there may be fundamental differences between their roles in human and mouse platelets has been proposed. Further, the recent recognition that Src family tyrosine kinases contribute to signaling by alpha2beta1 and other adhesive receptors, in addition to GPVI, has added to this debate. The present study compares the roles of alpha2beta1, GPVI, and Src-dependent kinases in supporting adhesion and aggregation in human and mouse platelets in whole blood using blocking antibodies, mutant mice, and a novel inhibitor of Src kinases, PD0173952, which is effective in plasma. The results demonstrate that the fundamental processes of adhesion and aggregate formation are conserved in mice and human platelets and that two mechanisms of stable adhesion and activation on collagen exist. These can be distinguished by the contributions of GPVI and alpha2beta1, with GPVI-mediated platelet activation either preceding or following integrin-mediated adhesion. The relative contribution of each pathway depends on environmental conditions and may also reflect platelet heterogeneity. These observations form the basis of a unifying two-state model of platelet adhesion and aggregate formation on collagen that is conserved between human and mouse platelets.Keywords
Funding Information
- British Heart Foundation
This publication has 36 references indexed in Scilit:
- The Platelet Collagen Receptor Glycoprotein VI Is a Member of the Immunoglobulin Superfamily Closely Related to FcαR and the Natural Killer ReceptorsPublished by Elsevier BV ,1999
- Specific Synergy of Multiple Substrate–Receptor Interactions in Platelet Thrombus Formation under FlowCell, 1998
- Physical and Functional Association of the Src Family Kinases Fyn and Lyn with the Collagen Receptor Glycoprotein VI-Fc Receptor γ Chain Complex on Human PlateletsThe Journal of Experimental Medicine, 1998
- A Novel Association of Fc Receptor γ-Chain with Glycoprotein VI and Their Co-expression as a Collagen Receptor in Human PlateletsPublished by Elsevier BV ,1997
- Platelet Adhesion to Collagen: an UpdateThrombosis and Haemostasis, 1997
- The Fc receptor γ-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagenThe EMBO Journal, 1997
- Tyrosine Phosphorylation of the Fc Receptor γ-Chain in Collagen-stimulated PlateletsPublished by Elsevier BV ,1996
- Platelet Adhesion to CollagenThrombosis and Haemostasis, 1995
- Distinct determinants on collagen support alpha 2 beta 1 integrin-mediated platelet adhesion and platelet activation.Cell Regulation, 1991
- Platelet-reactive sites in collagens type I and type III. Evidence for separate adhesion and aggregatory sitesBiochemical Journal, 1989