CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo

Wong, C, Liu, Y, Yip, C, Chand, R, Wee, J, Oates, L, Nieswandt, B, Reheman, A, Ni, H, Beauchemin, N and Jackson, D 2009, 'CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo', Blood, vol. 113, no. 8, pp. 1818-1828.


Document type: Journal Article
Collection: Journal Articles

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Title CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo
Author(s) Wong, C
Liu, Y
Yip, C
Chand, R
Wee, J
Oates, L
Nieswandt, B
Reheman, A
Ni, H
Beauchemin, N
Jackson, D
Year 2009
Journal name Blood
Volume number 113
Issue number 8
Start page 1818
End page 1828
Total pages 11
Publisher American Society of Hematology
Abstract 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 immunorecep-tor 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.
Subject Clinical Sciences not elsewhere classified
Keyword(s) C reactive protein
carcinoembryonic antigen related cell adhesion molecule 1
collagen
collagen type 1
Fc receptor
ferric chloride
glycoprotein VI
monoclonal antibody
DOI - identifier 10.1182/blood-2008-06-165043
Copyright notice © 2009 by The American Society of Hematology
ISSN 0006-4971
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