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J. Biol. Chem., Vol. 283, Issue 24, 16279-16282, June 13, 2008

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Redundant Mechanism of Platelet Adhesion to Laminin and Collagen under Flow

INVOLVEMENT OF VON WILLEBRAND FACTOR AND GLYCOPROTEIN Ib-IX-V^*

From the Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898 Japan

Although the role of collagen in thrombosis has been extensively investigated, the contribution of other extracellular matrices is still unclear. We have recently reported that laminin stimulates platelet spreading through integrin ₆β₁-dependent activation of the collagen receptor glycoprotein (GP) VI under static condition. Under physiological high and low shear conditions, platelets adhered to laminin, and this was strongly inhibited by an antibody that blocks association between GPIb-IX-V and von Willebrand factor (VWF). Moreover, platelets of type III von Willebrand disease or Bernard-Soulier syndrome adhered to laminin at a low shear condition but not at a high shear condition. The specific binding of laminin to VWF was confirmed by surface plasmin resonance spectroscopy (BIAcore). These findings suggest that laminin supports platelet adhesion depending on the interaction of VWF and GPIb-IX-V under pathophysiological high shear flow. This mechanism is similar to that of collagen. We propose that integrins, GPVI, GPIb-IX-V, and VWF represent a general paradigm for the interaction between platelets and subendothelial matrices.

Received for publication, December 28, 2007 , and in revised form, April 28, 2008.

^* This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants 17924029 and 18890077) (to O. I.), from the University of Yamanashi, Japan (to O. I.), and from the Mitsubishi Pharma Research Foundation, Japan (to O. I). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-55-273-9884; Fax: 81-55-273-6713; E-mail: oinoue{at}yamanashi.ac.jp.

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