title: CEACAM2 positively regulates integrin αIIbβ3-mediated platelet functions.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an Ig-ITIM superfamily member that regulates integrin αIIbβ3 function. We hypothesized 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 loss. Cc2-/-platelets have moderate integrin αIIbβ3-mediated functional defects with impaired kinetics of platelet spreading on fibrinogen and type I collagen and delayed kinetics in the retraction of fibrin clots in vitro. This functional integrin αIIbβ3 defect could not be attributed to altered integrin αIIbβ3 expression. Cc2-/-platelets displayed normal 'inside-out' signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)-fibrinogen and JON/A antibody binding. This data provides direct evidence that disruption of CEACAM2 induces a moderate integrin αIIbβ3-mediated platelet function defect, and that CEACAM2 is essential to maintain a normal integrin αIIbβ3-mediated platelet function.
authors.affiliation: a Thrombosis and Vascular Diseases Laboratory, School of Medical Sciences, RMIT University , Bundoora , Australia.
authors.forename: Musaed M
authors.initials: MM
authors.lastname: Alshahrani
authors.affiliation: a Thrombosis and Vascular Diseases Laboratory, School of Medical Sciences, RMIT University , Bundoora , Australia.
authors.forename: Roula P
authors.initials: RP
authors.lastname: Kyriacou
authors.affiliation: a Thrombosis and Vascular Diseases Laboratory, School of Medical Sciences, RMIT University , Bundoora , Australia.
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: O'Malley
authors.affiliation: b Department of Physiology , Center for Diabetes and Endocrine Research, University of Toledo , Toledo , OH , USA.|c Department of Pharmacology , College of Medicine and Life Sciences, University of Toledo , Toledo , OH , USA.
authors.forename: Garrett
authors.initials: G
authors.lastname: Heinrich
authors.affiliation: b Department of Physiology , Center for Diabetes and Endocrine Research, University of Toledo , Toledo , OH , USA.|c Department of Pharmacology , College of Medicine and Life Sciences, University of Toledo , Toledo , OH , USA.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Najjar
authors.affiliation: a Thrombosis and Vascular Diseases Laboratory, School of Medical Sciences, RMIT University , Bundoora , Australia.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Jackson
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003018:Clot Retraction; D051379:Mice; D018345:Mice, Knockout; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D019039:Platelet Glycoprotein GPIIb-IIIa Complex