Carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) is a surface glycoprotein expressed on various blood cells, epithelial cells, and vascular cells. CEACAM1 possesses adhesive and signaling properties mediated by its intrinsic immunoreceptor tyrosine-based inhibitory motifs that recruit SHP-1 protein-tyrosine phosphatase. In this study, we demonstrate that CEACAM1 is expressed on the surface and in intracellular pools of platelets. In addition, CEACAM1 serves to negatively regulate signaling of platelets by collagen through the glycoprotein VI (GPVI)/Fc receptor (FcR)-␥-chain. ceacam1 ؊/؊ platelets displayed enhanced type I collagen and GPVI-selective ligand, collagen-related peptide (CRP), CRPmediated platelet aggregation, enhanced platelet adhesion on type I collagen, and elevated CRP-mediated alpha and dense granule secretion. Platelets derived from ceacam1 ؊/؊ mice form larger thrombi when perfused over a collagen matrix under arterial flow compared with wild-type mice. Furthermore, using intravital microscopy to ferric chloride-injured mesenteric arterioles, we show that thrombi formed in vivo in ceacam1 ؊/؊ mice were larger and were more stable than those in wild-type mice. GPVI depletion using monoclonal antibody JAQ1 treatment of ceacam1 ؊/؊ mice showed a reversal in the more stable thrombus growth phenotype. ceacam1 ؊/؊ mice were more susceptible to type I collagen-induced pulmonary thromboembolism than wild-type mice. Thus, CEACAM1 acts as a negative regulator of platelet-collagen interactions and of thrombus growth involving the collagen GPVI receptor in vitro and in vivo. (Blood.

No abstract

Summary. Background: This study was designed to determine the role of CD151 in platelet thrombus formation in vivo and define the contribution of platelet vs. endothelial CD151 in regulating platelet thrombus formation in vivo. Methods and Results: Using intravital microscopy and ferric chloride (FeCl 3 ) injury of mesenteric arterioles, we found that thrombi formed in CD151 +/) and CD151 )/) mice were smaller and less stable, than those formed in CD151 +/+ mice, with a tendency for embolization. Similarly, in FoltÕs FeCl 3 )induced carotid injury model, both CD151 +/) and CD151 )/) mice showed more prolonged times to 95% vessel occlusion than CD151 +/+ mice. In addition, laser-induced injury of cremaster muscle arterioles showed that thrombi formed in CD151 +/) and CD151 )/) mice were smaller and less stable than those formed in CD151 +/+ mice. Following platelet depletion/reconstitution with ex vivolabeled donor platelets, platelet-depleted CD151 +/+ mice that received reconstitution with CD151 )/) platelets had smaller thrombi that were unstable and embolized. In contrast, plateletdepleted CD151 )/) mice that received reconstitution with CD151 +/+ platelets had normal thrombi that were stable. Conclusions: These data provide evidence that platelet CD151 is required for regulating thrombus formation in vivo.