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

Alshahrani, M, Yang, E, Yip, C, Ghanem, S, Abdallah, S, deAngelis, A, O'Malley, C, Moheimani, F, Najjar, S and Jackson, D 2014, 'CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo', Blood, vol. 124, no. 15, pp. 2431-2441.


Document type: Journal Article
Collection: Journal Articles

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Title CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo
Author(s) Alshahrani, M
Yang, E
Yip, C
Ghanem, S
Abdallah, S
deAngelis, A
O'Malley, C
Moheimani, F
Najjar, S
Jackson, D
Year 2014
Journal name Blood
Volume number 124
Issue number 15
Start page 2431
End page 2441
Total pages 11
Publisher American Society of Hematology
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)-FcRy-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 α 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.
Subject
DOI - identifier 10.1182/blood-2014-04-569707
Copyright notice © 2014 by The American Society of Hematology
ISSN 0006-4971
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