CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis

Blood - Tập 114 Số 16 - Trang 3464-3472 - 2009
Frauke May1, Ina Hagedorn1, Irina Pleines1, Markus Bender1, Timo Vögtle1, Johannes A. Eble2, Margitta Elvers1, Bernhard Nieswandt1
1University Clinic, University of Würzburg, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Würzburg; and
2Center for Molecular Medicine, Department of Vascular Matrix Biology, Excellence Cluster Cardio-Pulmonary System, Frankfurt University Hospital, Frankfurt, Germany

Tóm tắt

Abstract Damage to the integrity of the vessel wall leads to exposure of the subendothelial extracellular matrix (ECM), triggering platelet activation and aggregation. This process is essential for primary hemostasis but it may also lead to arterial thrombosis. Although the mechanisms underlying platelet activation on the ECM are well explored, it is less clear which receptors mediate cellular activation in a growing thrombus. Here we studied the role of the recently identified C-type lectin-like receptor 2 (CLEC-2) in this process. We show that anti–CLEC-2 antibody treatment of mice leads to complete and highly specific loss of CLEC-2 in circulating platelets for several days. CLEC-2–deficient platelets displayed normal adhesion under flow, but subsequent aggregate formation was severely defective in vitro and in vivo. As a consequence, CLEC-2 deficiency was associated with increased bleeding times and profound protection from occlusive arterial thrombus formation. These results reveal an essential function of CLEC-2 in hemostasis and thrombosis.

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Blood

Tập 114 Số 16

3464-3472

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