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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1492-1499. Prepublished online as a Blood First Edition Paper on October 26, 2004; DOI 10.1182/blood-2004-06-2391. This Article Full Text (PDF) All Versions of this Article: 2004-06-2391v1 105/4/1492    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 Gruner, S. Articles by Nieswandt, B. Search for Related Content PubMed PubMed Citation Articles by Gruner, S. Articles by Nieswandt, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 23, 2004 Accepted September 26, 2004 Relative antithrombotic effect of soluble GPVI dimer versus anti-GPVI antibodies in mice Sabine Gruner, Miroslava Prostredna, Martina Koch, Yoshiki Miura, Valerie Schulte, Stephanie M Jung, Masaaki Moroi, and Bernhard Nieswandt* Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume, Fukuoka, Japan * Corresponding author; email: bernhard.nieswandt{at}virchow.uni-wuerzburg.de. Glycoprotein (GP)VI is an essential platelet collagen receptor; therefore, the inhibition of GPVI-collagen interactions may be an attractive antithrombotic strategy. We have previously shown that targeting of GPVI with antibodies leads to depletion of the receptor and long-term antithrombotic protection in mice. An alternative agent to interfere with GPVI-collagen interactions might be soluble GPVI acting as a competitive inhibitor, thereby avoiding undesired effects on platelets. To test this, we expressed soluble dimeric human GPVI, comprising the extracellular domain of the receptor fused to human immunoglobulin Fc domain (GPVI-Fc) and compared its antithrombotic potential with that of anti-GPVI antibodies in mice. In contrast to a recent report, we found by intravital fluorescence microscopy and ultrasonic flow measurements that GPVI-Fc had no effect on platelet adhesion and thrombus formation at the injured arterial wall whereas anti-GPVI antibodies profoundly inhibited these processes. Similar results were obtained with a fusion protein comprising the extracellular domain of mouse GPVI and human IgG-Fc. This indicates that direct targeting of GPVI provides signifiantly stronger protection against arterial thrombosis than soluble GPVI dimer. 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