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Blood, 19 February 2009, Vol. 113, No. 8, pp. 1818-1828. Prepublished online as a Blood First Edition Paper on November 13, 2008; DOI 10.1182/blood-2008-06-165043. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-06-165043v1 113/8/1818    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wong, C. Articles by Jackson, D. E. Search for Related Content PubMed PubMed Citation Articles by Wong, C. Articles by Jackson, D. E. Related Collections Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo Cyndi Wong1,*, Yong Liu1,*, Jana Yip1, Rochna Chand1, Janet L. Wee1, Lisa Oates1, Bernhard Nieswandt2, Adili Reheman3, Heyu Ni3, Nicole Beauchemin4, and Denise E. Jackson1 1 Burnet Institute incorporating the Austin Research Institute, Heidelberg, Australia; 2 Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany; 3 Department of Laboratory Medicine and Pathobiology, St Michael's Hospital, University of Toronto and Canadian Blood Services, Toronto, ON; and 4 McGill Cancer Centre, McGill University, Montreal, QC 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), CRP-mediated 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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