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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-05-1391.

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Submitted May 5, 2003
Accepted July 22, 2003

Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo

Sabine Gruner, Miroslava Prostredna, Valerie Schulte, Thomas Krieg, Beate Eckes, Cord Brakebusch, and Bernhard Nieswandt*

Rudolf Virchow Center for Experimental Biomedicine, University of Wuersburg, Wuerzburg, Germany
Department of Dermatology, University of Cologne, Cologne, Germany
Department of Molecular Medicine, Max-Planck-Institute for Biochemistry, Martinsried, Germany

* Corresponding author; email: bernhard.nieswandt{at}@virchow.uni-wuerzburg.de.

Damage to the integrity of the vessel wall results in exposure of the subendothelial extracellular matrix (ECM), which triggers integrin-dependent adhesion and aggregation of platelets. The role of platelet {beta}1 integrins in these processes remains mostly undefined. Here, we demonstrate by intravital fluorescence microscopy that platelet adhesion and thrombus growth on the exposed ECM of the injured carotid artery is not significantly altered in {alpha}2-null mice and even in mice with a Cre/loxP-mediated loss of all {beta}1 integrins on their platelets. In contrast, inhibition of {alpha}IIb{beta}3 integrin on platelets in wild type mice blocked aggregate formation and reduced platelet adhesion by 60.0%. Strikingly, {alpha}IIb{beta}3 inhibition had a comparable effect in {alpha}2-null mice, demonstrating that other receptors mediate shear-resistant adhesion in the absence of functional {alpha}2{beta}1 and {alpha}IIb{beta}3. These were identified to be {alpha}5{beta}1 and/or {alpha}6{beta}1 as {alpha}IIb{beta}3 inhibition abrogated platelet adhesion in {beta}1-null mice. We conclude that shear-resistant platelet adhesion on the injured vessel wall in vivo is a highly integrated process involving multiple integrin-ligand interactions, none of which by itself is essential.


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