title: CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis.
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.
authors.affiliation: University Clinic, University of Würzburg, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Würzburg, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: May
authors.forename: Ina
authors.initials: I
authors.lastname: Hagedorn
authors.forename: Irina
authors.initials: I
authors.lastname: Pleines
authors.forename: Markus
authors.initials: M
authors.lastname: Bender
authors.forename: Timo
authors.initials: T
authors.lastname: Vögtle
authors.forename: Johannes
authors.initials: J
authors.lastname: Eble
authors.forename: Margitta
authors.initials: M
authors.lastname: Elvers
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D000906:Antibodies; C529518:CLEC-2 protein, mouse; D037181:Lectins, C-Type