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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1268-1277. Prepublished online as a Blood First Edition Paper on May 10, 2005; DOI 10.1182/blood-2004-11-4434. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-11-4434v1 106/4/1268    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 Sarratt, K. L Articles by Kahn, M. L Search for Related Content PubMed PubMed Citation Articles by Sarratt, K. L Articles by Kahn, M. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 19, 2004 Accepted April 14, 2005 GPVI and 21 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow Kendra L Sarratt, Hong Chen, Mary M Zutter, Samuel A Santoro, Daniel A Hammer, and Mark L Kahn* Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA Department of Medicine, Division of Cardiology, University of Pennsylvania, Philadelphia, PA, USA Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA * Corresponding author; email: markkahn{at}mail.med.upenn.edu. The roles of the two major platelet collagen receptors, glycoprotein VI (GPVI) and integrin 21, have been intensely investigated using a variety of methods over the past decade. In the present study, we have used pharmacologic and genetic approaches to study human and mouse platelet adhesion to collagen under flow conditions. Our studies demonstrate that both GPVI and integrin 21 play significant roles for platelet adhesion to collagen under flow and that the loss of both receptors completely ablates this response. Intracellular signaling mediated by the cytoplasmic adaptor SLP-76 but not by the transmembrane adaptor LAT is critical for platelet adhesion to collagen under flow. In addition, reduced GPVI receptor density results in severe defects in platelet adhesion to collagen under flow. Defective adhesion to collagen under flow is associated with prolonged tail bleeding times in mice lacking one or both collagen receptors. These studies establish platelet collagen responses under physiologic flow as the consequence of a close partnership between two structurally distinct receptors and suggest that both receptors play significant hemostatic roles in vivo. 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