The Journal of Experimental Medicine
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Published online 23 December 2002 doi:10.1084/jem.20020945
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© Rockefeller University Press, 0022-1007/2003/1/41 $5.00
The Journal of Experimental Medicine, Volume 197, Number 1, 41-49

A Crucial Role of Glycoprotein VI for Platelet Recruitment to the Injured Arterial Wall In Vivo

Steffen Massberg1, Meinrad Gawaz1, Sabine Grüner1, Valerie Schulte2, Ildiko Konrad1, Dietlind Zohlnhöfer1, Ulrich Heinzmann3 and Bernhard Nieswandt2

1 Deutsches Herzzentrum und 1. Medizinische Klinik, Technische Universität München, D-80636 München, Germany
2 Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, 97078 Würzburg, Germany
3 GSF National Research Center for Environment and Health, Institute of Pathology, D-85764 Neuherberg, Germany

Address correspondence to Bernhard Nieswandt, Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany. Phone: 49-931-201-48996; Fax: 49-931-201-48978; E-mail: bernhard.nieswandt{at}virchow.uni-wuerzburg.de; or Meinrad Gawaz, Deutsches Herzzentrum und 1. Medizinische Klinik, Technische Universität München, Lazarettstraße 36, D-80636 München, Germany. Phone: 49-89-1218-4012; Fax: 49-89-1218-4003; E-mail: gawaz{at}dhm.mhn.de

Platelet adhesion and aggregation at sites of vascular injury is crucial for hemostasis but may lead to arterial occlusion in the setting of atherosclerosis and precipitate diseases such as myocardial infarction. A current hypothesis suggests that platelet glycoprotein (GP) Ib interaction with von Willebrand factor recruits flowing platelets to the injured vessel wall, where subendothelial fibrillar collagens support their firm adhesion and activation. However, so far this hypothesis has not been tested in vivo. Here, we demonstrate by intravital fluorescence microscopy of the mouse carotid artery that inhibition or absence of the major platelet collagen receptor, GPVI, abolishes platelet–vessel wall interactions after endothelial denudation. Unexpectedly, inhibition of GPVI by the monoclonal antibody JAQ1 reduced platelet tethering to the subendothelium by ~89%. In addition, stable arrest and aggregation of platelets was virtually abolished under these conditions. Using different models of arterial injury, the strict requirement for GPVI in these processes was confirmed in GPVI-deficient mice, where platelets also failed to adhere and aggregate on the damaged vessel wall. These findings reveal an unexpected role of GPVI in the initiation of platelet attachment at sites of vascular injury and unequivocally identify platelet–collagen interactions (via GPVI) as the major determinant of arterial thrombus formation.

Key Words: arterial thrombosis • collagen • receptor • GPVI • mouse


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