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Blood, 1 August 2006, Vol. 108, No. 3, pp. 908-914. Prepublished online as a Blood First Edition Paper on March 28, 2006; DOI 10.1182/blood-2005-07-2937. This Article Full Text (PDF) All Versions of this Article: 2005-07-2937v1 108/3/908    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 Boylan, B. Articles by Newman, P. J Search for Related Content PubMed PubMed Citation Articles by Boylan, B. Articles by Newman, P. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 21, 2005 Accepted March 13, 2006 Activation-independent, antibody-mediated removal of GPVI from circulating human platelets: Development of a novel NOD/SCID mouse model to evaluate the in vivo effectiveness of anti-human platelet agents Brian Boylan, Michael C Berndt, Mark L Kahn, and Peter J Newman* Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA; Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Cellular Biology, Medical College of Wisconsin, Milwaukee, WI, USA * Corresponding author; email: peter.newman{at}bcw.edu. GPVI is a 62 kDa membrane glycoprotein expressed in non-covalent association with the Fc receptor chain on human and murine platelets, and serves as the major activating receptor for collagen. GPVI-specific antibodies have the capacity to specifically deplete GPVI from mouse and human platelets in vivo, rendering them unresponsive to collagen and GPVI-specific agonists. Such antibodies do not remove GPVI from non-circulating platelets in vitro, however, making it difficult to evaluate their anti-thrombotic potential and mechanism of action, particularly in human platelets. We devised a model system in which human platelets are introduced into the retro-orbital plexus of NOD/SCID mice, allowed to circulate, and evaluated for the effects of GPVI-specific murine monoclonal antibodies (mAbs) on platelet survival and function. GPVI-specific mAbs triggered depletion of GPVI from human, but not murine, platelets. Soluble truncated human GPVI appeared concomitantly in mouse plasma. GPVI-depleted human platelets had markedly diminished responses to GPVI-specific agonists, and unexpectedly exhibited somewhat depressed responses to G-protein-coupled agonists. The ability to evaluate in living mice the in vivo function and survival of circulating human platelets may prove valuable for determining mechanisms of antibody-mediated platelet passivation, and aid in the development of novel anti-platelet therapeutics. 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. Eble, M. Elvers, and B. Nieswandt CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis Blood, October 15, 2009; 114(16): 3464 - 3472. [Abstract] [Full Text] [PDF] H. H. Wandall, K. M. Hoffmeister, A. L. Sorensen, V. Rumjantseva, H. Clausen, J. H. Hartwig, and S. J. 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