beta(2)-glycoprotein I binding to platelet microparticle membrane specifically reduces immunoreactivity of glycoproteins IIb/IIIa

We have investigated beta (2)-glycoprotein I (beta (2)GPI) binding to plate let-derived microparticles (PMP) and its effect on GPIIb/IIIa, PMP were iso lated from washed human platelets after stimulation with A23187, and analyz ed by surface plasmon resonance spectroscopy. beta (2)GPI as well as activa ted protein C (APC) or annexin V bound to PMP-coated sensorchips. demonstra ting exposure of anionic phospholipids on immobilized PMP. beta (2)GPI bind ing was impaired by calcium and occurred in a concentration-dependent manne r with apparent k(on) = 2.6 X 10(4) M-1.s(-1) and k(off) = 4.4 X 10(-3) s(- 1), corresponding to a K-D value of 1.7 X 10(-7) M. When analyzed by flow c ytometry, the binding of certain mAbs specific for GPIIb and/or GPIIIa was reduced in the presence of beta (2)GPI 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 o f beta (2)GPI on GPIIb/IIIa immunoreactivity, and indicate that beta (2)GPI may act as a modulator of GPIIb/IIIa-dependent Functions of PMP.