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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1741-1746. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-07-2267. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2267v1 103/5/1741    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 Keuren, J. F. W. Articles by Lindhout, T. Search for Related Content PubMed PubMed Citation Articles by Keuren, J. F. W. Articles by Lindhout, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Von Willebrand factor C1C2 domain is involved in platelet adhesion to polymerized fibrin at high shear rate Jeffrey F. W. Keuren, Dominique Baruch, Paulette Legendre, Cécile V. Denis, Peter J. Lenting, Jean-Pierre Girma, and Theo Lindhout From the Department of Biochemistry, Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) U.143, Le Kremlin Bicêtre, Paris, France; and Laboratory for Thrombosis and Hemostasis, Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. Fibrin is actively involved in platelet reactions essential for thrombus growth, in which von Willebrand factor (VWF) might be an important mediator. The aim of this study was to localize VWF domains that bind to fibrin and to determine their relevance in platelet adhesion. VWF binds specifically to fibrin with an apparent Kd of 2.2 µg/mL. Competition in the presence of 2 complementary fragments, SpIII (residues 1-1365) and SpII (residues 1366-2050), indicated that the high affinity binding site for fibrin is located in the C-terminal part, thus distinct from the A domains. Comparison of 2 deleted rVWF (D4B-rVWF, C1C2-rVWF) suggested that the C1C2 domains contained a fibrin binding site. This site is distinct from RGD, as shown by binding of D1746G-rVWF to fibrin. Perfusion studies at high shear rate demonstrated that C1C2 domains were required for optimal platelet adhesion to fibrin. With the use of a VWF-deficient mouse model, it was found that plasma VWF is critical for platelet tethering and adhesion to fibrin. These results suggest a dual role of fibrin-bound VWF in thrombus formation: first, fibrin-bound VWF is critical in the recruitment of platelets by way of glycoprotein (GP) Ib, and, second, it contributes to stationary platelet adhesion by way of binding to activated IIb3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. T. Roberts, H. Ghebeh, M. A. Chishti, F. Al-Mohanna, R. El-Sayed, F. Al-Mohanna, and A. Bouchama Microvascular Injury, Thrombosis, Inflammation, and Apoptosis in the Pathogenesis of Heatstroke: A Study in Baboon Model Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1130 - 1136. [Abstract] [Full Text] [PDF] H. Choi, K. Aboulfatova, H. J. Pownall, R. Cook, and J.-f. Dong Shear-induced Disulfide Bond Formation Regulates Adhesion Activity of von Willebrand Factor J. Biol. Chem., December 7, 2007; 282(49): 35604 - 35611. [Abstract] [Full Text] [PDF]

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