Platelet adhesion to dimeric beta(2)-glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ib alpha and apolipoprotein E receptor 2 '
Pennings, M. T. T × Derksen, R. H. W. M Van Lummel, M Adelmeijer, J Vanhoorelbeke, Karen Urbanus, R. T Lisman, T De Groot, P. G #
Journal of thrombosis and haemostasis vol:5 issue:2 pages:369-377
Background: The major antigen implicated in the antiphospholipid syndrome is beta2-glycoprotein I (beta(2)GPI). Dimerized beta(2)GPI binds to apolipoprotein E receptor 2' (apoER2') on platelets and increases platelet adhesion to collagen under conditions of flow. Aim: To investigate whether the interaction between dimerized beta(2)GPI and platelets is sufficiently strong to resist shear stresses. Methods: We studied the interaction of platelets with immobilized dimerized beta(2)GPI under conditions of flow, and further analyzed the interaction using surface plasmon resonance and solid phase immunoassays. Results: We found that dimerized beta(2)GPI supports platelet adhesion and aggregate formation under venous flow conditions. Adhesion of platelets to dimerized beta(2)GPI was completely inhibited by the addition of soluble forms of both apoER2' and GPIb alpha, and the addition of receptor-associated protein and the removal of GPIb alpha from the platelet surface. GPIb alpha co-precipitated with apoER2', suggesting the presence of complexes between GPIb alpha and apoER2' on platelet membranes. The interaction between GPIb alpha and dimeric beta(2)GPI was of intermediate affinity (K-d = 180 nM) and Zn2+, but not Ca2+-dependent. Deletion of domain V from dimeric beta(2)GPI strongly reduced its binding to both GPIb alpha and apoER2'. Antibodies that inhibit the binding of thrombin to GPIb alpha inhibited platelet adhesion to dimeric beta(2)GPI completely, while antibodies blocking the binding of von Willebrand factor to GPIb alpha had no effect. Dimeric beta(2)GPI showed reduced binding to low-sulfated GPIb alpha compared to the fully sulfated form. Conclusion: We show that platelets adhere to dimeric beta(2)GPI under both arterial and venous shear stresses. Platelets adhere via two receptors: GPIb alpha and apoER2'. These receptors are present in a complex on the platelet surface.