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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-10-3242. This Article Full Text (PDF) All Versions of this Article: 2002-10-3242v1 101/10/3948    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 Schulte, V. Articles by Nieswandt, B. Search for Related Content PubMed PubMed Citation Articles by Schulte, V. Articles by Nieswandt, B. Social Bookmarking                   What's this? Submitted October 28, 2002 Accepted January 2, 2003 Targeting of the collagen-binding site on glycoprotein VI is not essential for in vivo depletion of the receptor Valerie Schulte, Tamer Rabie, Miroslava Prostredna, Barsom Aktas, Sabine Gruener, and Bernhard Nieswandt* Department of Vascular Biology, Rudolf Virchow Center, University of Wuerzburg, Wuerzburg, Germany * Corresponding author; email: bernhard.nieswandt{at}virchow.uni-wuerzburg.de. Glycoprotein (GP) VI is an essential collagen receptor on platelets and may serve as an attractive target for antithrombotic therapy. We have previously shown that a monoclonal antibody (mAb) against the major collagen binding site on mouse GPVI (JAQ1) induces irreversible down-regulation of the receptor and, consequently, long-term antithrombotic protection in vivo. To determine whether this unique in vivo effect of JAQ1 is based on its interaction with the ligand binding site on GPVI, we generated new mAbs against different epitopes on GPVI (JAQ2, JAQ3) and tested their in vitro and in vivo activity. We show that none of the mAbs inhibited platelet activation by collagen or the collagen related peptide in vitro. Unexpectedly, however, injection of either antibody induced depletion of GPVI with the same efficacy and kinetics as JAQ1. Importantly, this effect was also seen with monovalent F(ab) fragments of JAQ2 and JAQ3, excluding the involvement of the Fc part or the dimeric form of anti-GPVI antibodies in this process. This indicates that anti-GPVI agents, irrespective of their binding site may generally induce down-regulation of the receptor in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. May, I. Hagedorn, I. Pleines, M. Bender, T. Vogtle, J. 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