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Platelet adhesion to dimeric β 2 ‐glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ib α and apolipoprotein E receptor 2′
Author(s) -
PENNINGS M. T. T.,
DERKSEN R. H. W. M.,
VAN LUMMEL M.,
ADELMEIJER J.,
VANHOORELBEKE K.,
URBANUS R. T.,
LISMAN T.,
DE GROOT P. G.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02310.x
Subject(s) - platelet , chemistry , von willebrand factor , platelet membrane glycoprotein , receptor , biophysics , glycoprotein , platelet glycoprotein gpib ix complex , thrombin , glycoprotein ib , platelet activation , microbiology and biotechnology , biochemistry , immunology , biology
Summary. Background: The major antigen implicated in the antiphospholipid syndrome is beta2‐glycoprotein I (β 2 GPI). Dimerized β 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 β 2 GPI and platelets is sufficiently strong to resist shear stresses. Methods: We studied the interaction of platelets with immobilized dimerized β 2 GPI under conditions of flow, and further analyzed the interaction using surface plasmon resonance and solid phase immunoassays. Results: We found that dimerized β 2 GPI supports platelet adhesion and aggregate formation under venous flow conditions. Adhesion of platelets to dimerized β 2 GPI was completely inhibited by the addition of soluble forms of both apoER2′ and GPIbα, and the addition of receptor‐associated protein and the removal of GPIbα from the platelet surface. GPIbα co‐precipitated with apoER2′, suggesting the presence of complexes between GPIbα and apoER2′ on platelet membranes. The interaction between GPIbα and dimeric β 2 GPI was of intermediate affinity ( K d = 180 n m ) and Zn 2+ , but not Ca 2+ ‐dependent. Deletion of domain V from dimeric β 2 GPI strongly reduced its binding to both GPIbα and apoER2′. Antibodies that inhibit the binding of thrombin to GPIbα inhibited platelet adhesion to dimeric β 2 GPI completely, while antibodies blocking the binding of von Willebrand factor to GPIbα had no effect. Dimeric β 2 GPI showed reduced binding to low‐sulfated GPIbα compared to the fully sulfated form. Conclusion: We show that platelets adhere to dimeric β 2 GPI under both arterial and venous shear stresses. Platelets adhere via two receptors: GPIbα and apoER2′. These receptors are present in a complex on the platelet surface.