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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 (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 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 Articles by Lindhout, T. Search for Related Content PubMed PubMed Citation Articles by Keuren, J. F Articles by Lindhout, T. Social Bookmarking                   What's this? Submitted July 7, 2003 Accepted October 29, 2003 Von Willebrand factor C1C2 domain is involved in platelet adhesion to polymerized fibrin at high shear rate Jeffrey F Keuren, Dominique Baruch, Paulette Legendre, Cecile V Denis, Peter J Lenting, Jean-Pierre Girma, and Theo Lindhout* Department of Biochemistry, Maastricht University, Maastricht, The Netherlands Unite 143, INSERM, Paris, France Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands * Corresponding author; email: t.lindhout{at}bioch.unimaas.nl. Fibrin is actively involved in platelet reactions essential for thrombus growth, where VWF might be an essential 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 two 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 two 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. Utilizing a VWF-deficient mouse model, it was found that plasma VWF was critical in shortening the time lag for platelet tethering and adhesion to fibrin. These results suggest a dual role of fibrin-bound VWF in thrombus formation: firstly, fibrin-bound vWF is critical in the recruitment of platelets via GP Ib and secondly, it contributes to stationary platelet adhesion via 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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