Abstract
AbstractCarcinoembryonic antigen–related cell adhesion molecule-2 (CEACAM2) is a cell-surface glycoprotein expressed on blood, epithelial, and vascular cells. CEACAM2 possesses adhesive and signaling properties mediated by immunoreceptor tyrosine-based inhibitory motifs. In this study, we demonstrate that CEACAM2 is expressed on the surface and in intracellular pools of platelets. Functional studies of platelets from Ceacam2−/−-deficient mice (Cc2−/−) revealed that CEACAM2 serves to negatively regulate collagen glycoprotein VI (platelet) (GPVI)-FcRγ–chain and the C-type lectinlike receptor 2 (CLEC-2) signaling. Cc2−/− platelets displayed enhanced GPVI and CLEC-2–selective ligands, collagen-related peptide (CRP), collagen, and rhodocytin (Rhod)-mediated platelet aggregation. They also exhibited increased adhesion on type I collagen, and hyperresponsive CRP and CLEC-2–induced α and dense granule release compared with wild-type platelets. Furthermore, using intravital microscopy to ferric chloride (FeCl3)–injured mesenteric arterioles and laser-induced injury of cremaster muscle arterioles, we herein show that thrombi formed in Cc2−/− mice were larger and more stable than wild-type controls in vivo. Thus, CEACAM2 is a novel platelet immunoreceptor that acts as a negative regulator of platelet GPVI-collagen interactions and of ITAM receptor CLEC-2 pathways.
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