The Journal of Experimental Medicine
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Published online 11 August 2003 doi:10.1084/jem.20030144
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© Rockefeller University Press, 0022-1007/2003/8/661 $5.00
The Journal of Experimental Medicine, Volume 198, Number 4, 661-667

Brief Definitive Report

 A Role of the Fast ATP-gated P2X1 Cation Channel in Thrombosis of Small Arteries In Vivo

Béatrice Hechler1, Nadège Lenain1, Patrizia Marchese2, Catherine Vial4, Véronique Heim1, Monique Freund1, Jean-Pierre Cazenave1, Marco Cattaneo2,3, Zaverio M. Ruggeri2, Richard Evans4 and Christian Gachet1

1 Institut National de la Santé et de la Recherche Médicale (INSERM) U.311, Etablissement Français du Sang (EFS)-Alsace, 67065 Strasbourg Cedex, France
2 The Scripps Research Institute, La Jolla, CA 92037
3 Unit of Hematology and Thrombosis, Ospedale San Paolo, Dipartimento di Medicina Chirurgia e Odontoiatria, University of Milan, 20142 Italy
4 Department of Cell Physiology and Pharmacology, University of Leicester, LE1 9HN Leicester, United Kingdom

Address correspondence to C. Gachet, INSERM U.311, EFS-Alsace 10, rue Spielmann, BP No. 36, 67065 Strasbourg Cedex, France. Phone: 33-388-21-25-25; Fax: 33-388-21-25-21; email: christian.gachet{at}efs-alsace.fr

The P2X1 receptor is a fast ATP-gated cation channel expressed in blood platelets, where its role has been difficult to assess due to its rapid desensitization and the lack of pharmacological tools. In this paper, we have used P2X1-/- and wild-type mouse platelets, treated with apyrase to prevent desensitization, to demonstrate the function of P2X1 in the response to thrombogenic stimuli. In vitro, the collagen-induced aggregation and secretion of P2X1-deficient platelets was decreased, as was adhesion and thrombus growth on a collagen-coated surface, particularly when the wall shear rate was elevated. In vivo, the functional role of P2X1 could be demonstrated using two models of platelet-dependent thrombotic occlusion of small arteries, in which blood flow is characterized by a high shear rate. The mortality of P2X1-/- mice in a model of systemic thromboembolism was reduced and the size of mural thrombi formed after a laser-induced vessel wall injury was decreased as compared with normal mice, whereas the time for complete thrombus removal was shortened. Overall, the P2X1 receptor appears to contribute to the formation of platelet thrombi, particularly in arteries in which shear forces are high.

Key Words: platelet • P2 receptors • arterial thrombosis • knockout mice • shear forces


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