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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4346-4353. Prepublished online as a Blood First Edition Paper on January 3, 2006; DOI 10.1182/blood-2005-10-4244. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4244v1 107/11/4346    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mangin, P. Articles by Jackson, S. P. Search for Related Content PubMed PubMed Citation Articles by Mangin, P. Articles by Jackson, S. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcR deficiency Pierre Mangin, Cindy L. Yap, Christelle Nonne, Sharelle A. Sturgeon, Isaac Goncalves, Yuping Yuan, Simone M. Schoenwaelder, Christine E. Wright, Francois Lanza, and Shaun P. Jackson From the Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia; Institut National de la Santé et de la Recherche Médicale (INSERM) U.311, Etablissement Français du Sang (EFS), Strasbourg, France; and the Department of Pharmacology, University of Melbourne, Victoria, Australia. Fibrillar collagens are among the most potent activators of platelets and play an important role in the initiation of thrombosis. The glycoprotein VI (GPVI)/FcR-chain complex is a central collagen receptor and inhibitors of GPVI produce a major defect in arterial thrombogenesis. In this study we have examined arterial thrombus formation in mice lacking the GPVI/FcR-chain complex (FcR–/–). Using 3 distinct arterial thrombosis models involving deep vascular injury, we demonstrate that deficiency of GPVI/FcR is not associated with a major defect in arterial thrombus formation. In contrast, with milder vascular injury deficiency of GPVI/FcR was associated with a 30% reduction in thrombus growth. Analysis of FcR–/– platelets in vitro, using thrombin-dependent and -independent thrombosis models, demonstrated a major role for thrombin in overcoming the thrombosis defect associated with GPVI/FcR deficiency. Inhibition of thrombin in vivo produced a much greater defect in thrombus formation in mice lacking GPVI/FcR compared with normal controls. Similarly, thrombin inhibition produced a marked prolongation in bleeding time in FcR–/– mice relative to wild-type mice. Our studies define an important role for thrombin in overcoming the hemostatic and thrombotic defect associated with GPVI/FcR deficiency. Moreover, they raise the interesting possibility that the full antithrombotic potential of GPVI receptor antagonists may only be realized through the concurrent administration of anticoagulant agents. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: GPVI: no magic bullet for thrombosis Mark L. Kahn Blood 2006 107: 4199. [Full Text] [PDF] This article has been cited by other articles: A. Ono, E. Westein, S. Hsiao, W. S. Nesbitt, J. R. Hamilton, S. M. Schoenwaelder, and S. P. 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Identification of a Unique Co-operative Phosphoinositide 3-Kinase Signaling Mechanism Regulating Integrin {alpha}IIbbeta3 Adhesive Function in Platelets J. Biol. Chem., September 28, 2007; 282(39): 28648 - 28658. [Abstract] [Full Text] [PDF] T. Rabie, D. Varga-Szabo, M. Bender, R. Pozgaj, F. Lanza, T. Saito, S. P. Watson, and B. Nieswandt Diverging signaling events control the pathway of GPVI down-regulation in vivo Blood, July 15, 2007; 110(2): 529 - 535. [Abstract] [Full Text] [PDF] Z. M. Ruggeri and G. L. Mendolicchio Adhesion Mechanisms in Platelet Function Circ. Res., June 22, 2007; 100(12): 1673 - 1685. [Abstract] [Full Text] [PDF] H. Li, S. Lockyer, A. Concepcion, X. Gong, H. Takizawa, M. Guertin, Y. Matsumoto, J. Kambayashi, N. N. Tandon, and Y. Liu The Fab Fragment of a Novel Anti-GPVI Monoclonal Antibody, OM4, Reduces In Vivo Thrombosis Without Bleeding Risk in Rats Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1199 - 1205. [Abstract] [Full Text] [PDF] C. Grothusen, S. Umbreen, I. Konrad, K. Stellos, C. Schulz, B. Schmidt, E. Kremmer, O. Teebken, S. Massberg, M. Luchtefeld, et al. EXP3179 Inhibits Collagen-Dependent Platelet Activation via Glycoprotein Receptor-VI Independent of AT1-Receptor Antagonism: Potential Impact on Atherothrombosis Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1184 - 1190. [Abstract] [Full Text] [PDF] U. J.H. Sachs and B. Nieswandt In Vivo Thrombus Formation in Murine Models Circ. Res., April 13, 2007; 100(7): 979 - 991. [Abstract] [Full Text] [PDF] C. V. Denis and D. D. Wagner Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 728 - 739. [Abstract] [Full Text] [PDF] S. C. Hughan, C. E. Hughes, O. J.T. McCarty, E. Schweighoffer, I. Soultanova, J. Ware, V. L.J. Tybulewicz, and S. P. Watson GPVI Potentiation of Platelet Activation by Thrombin and Adhesion Molecules Independent of Src Kinases and Syk Arterioscler. Thromb. 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