β₂-glycoprotein I Binding to Platelet Microparticle Membrane Specifically Reduces Immunoreactivity of Glycoproteins IIb/IIIa

Summary

We have investigated β₂-glycoprotein I (β₂GPI) binding to platelet-derived microparticles (PMP) and its effect on GPIIb/IIIa. PMP were isolated from washed human platelets after stimulation with A23187, and analyzed by surface plasmon resonance spectroscopy. β₂GPI as well as activated protein C (APC) or annexin V bound to PMP-coated sensorchips, demonstrating exposure of anionic phospholipids on immobilized PMP. β₂GPI binding was impaired by calcium and occurred in a concentration-dependent manner with apparent k_on = 2.610⁴ M^-1.s^-1 and k_off = 4.410^-3 s^-1, corresponding to a K_D value of 1.710^-7 M. When analyzed by flow cytometry, the binding of certain mAbs specific for GPIIb and/or GPIIIa was reduced in the presence of β₂GPI but not of APC or annexin V, whereas the binding of anti-GPIb or anti-P-selectin mAbs, or of soluble fibrinogen remained unchanged. These results suggest a broad but specific influence of β₂GPI on GPIIb/IIIa immunoreactivity, and indicate that β₂GPI may act as a modulator of GPIIb/IIIa-dependent functions of PMP.

Keywords

β₂-glycoprotein I - platelet microparticles - glycoproteins IIb/IIIa

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