CEACAM2 positively regulates integrin alpha(IIb)beta(3)-mediated platelet functions

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), is an Ig-ITIM superfamily member that regulates integrin alphaIIbbeta3 function. We hypothesised that its twin protein, CEACAM2, exerts a similar physiologic role in murine platelets. Ceacam2-deficient mice (Cc2-/-) displayed prolonged tail bleeding times and increased volume of blood lost. Cc2-/- platelets have moderate integrin alphaIIbbeta3 mediated functional defects with impaired kinetics of platelet spreading on fibrinogen and type I collagen and delayed kinetics in retraction of fibrin clots in vitro. This functional integrin alphaIIbbeta3 defect could not be attributed to altered integrin alphaIIbbeta3 expression. Cc2-/- platelets displayed normal 'inside-out' signalling properties as demonstrated by normal agonist-induced binding of soluble FITC-fibrinogen and JON/A antibody binding. This data provides direct evidence that disruption of CEACAM2 induces a moderate integrin alphaIIbbeta3-mediated platelet function defect, and that CEACAM2