CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo

Musaed M. Alshahrani, Eunice Yang, Jana Yip, Simona S. Ghanem, Simon L. Abdallah, Anthony M. De Angelis, Cindy J. O'Malley, Fatemeh Moheimani, Sonia M. Najjar, Denise E. Jackson

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    Abstract

    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)-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 a 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.

    Original languageEnglish
    Pages (from-to)2431-2441
    Number of pages11
    JournalBlood
    Volume124
    Issue number15
    DOIs
    Publication statusPublished - 9 Oct 2014

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