| First Author | Alshahrani MM | Year | 2014 |
| Journal | Blood | Volume | 124 |
| Issue | 15 | Pages | 2431-41 |
| PubMed ID | 25085348 | Mgi Jnum | J:218111 |
| Mgi Id | MGI:5616683 | Doi | 10.1182/blood-2014-04-569707 |
| Citation | Alshahrani MM, et al. (2014) CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo. Blood 124(15):2431-41 |
| abstractText | Carcinoembryonic 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)-FcRgamma-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 alpha 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. |
