CEACAM1 regulates integrin alphallbbeta3-mediated functions in platelets

Yip, C, Alshahrani, M, Beauchemin, N and Jackson, D 2015, 'CEACAM1 regulates integrin alphallbbeta3-mediated functions in platelets', Platelets, vol. 27, no. 2, pp. 168-177.


Document type: Journal Article
Collection: Journal Articles

Title CEACAM1 regulates integrin alphallbbeta3-mediated functions in platelets
Author(s) Yip, C
Alshahrani, M
Beauchemin, N
Jackson, D
Year 2015
Journal name Platelets
Volume number 27
Issue number 2
Start page 168
End page 177
Total pages 10
Publisher Informa Healthcare
Abstract Previous studies have implicated that the Ig-ITIM superfamily member, CEACAM1 may regulate integrin function. While CEACAM1 has been demonstrated to play a role as an inhibitory co-receptor of ITAM-associated GPVI/FcR g-chain signaling pathways in platelets, its physiologic role in integrin alphallbbeta3-mediated platelet function is unclear. In this study, we investigate the functional importance of Ceacam1 in murine platelets. We show that CEACAM1 is constitutively associated with integrin alphallbbeta3 in resting human and mouse platelets as demonstrated by co-immunoprecipitation studies. Using Ceacam1-deficient mice, we show that they have prolonged tail bleeding times and volume of blood lost that is corrected by reconstitution with platelet Ceacam1. Ceacam1/ platelets have moderate integrin alphallbbeta3-mediated functional defects with impaired kinetics of platelet spreading on fibrinogen and failure to retract fibrin clots in vitro. This functional integrin alphallbbeta3 defect could not be attributed to altered integrin alphallbbeta3 expression. Ceacam1/ platelets displayed normal ''inside-out'' signaling properties as demonstrated by normal agonist-induced binding of soluble (fluorescein isothiocyanate) FITCfibrinogen, JON/A antibody binding, and increases in cytosolic free calcium levels. This study provides direct evidence that Ceacam1 is essential for normal integrin alphallbbeta3-mediated platelet function and that disruption of mouse Ceacam1 induced moderate integrin alphallbbeta3-mediated functional defects.
Subject Haematology
Clinical Sciences not elsewhere classified
Keyword(s) CEACAM1
integrin aIIbb3 platelet functional defects
DOI - identifier 10.3109/09537104.2015.1064102
Copyright notice © 2015 Crown Copyright.
ISSN 0953-7104
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