The interaction of β 2 -glycoprotein I with lysophosphatidic acid in platelet aggregation and blood clotting.

β2 -Glycoprotein I (β2 -GPI) is a plasma protein that binds to oxidized low-density lipoprotein (LDL) and negatively charged substances, and inhibits platelet activation and blood coagulation. In this study, we investigated the interaction of β2 -GPI with a negatively charged lysophosphatidic acid (LPA) in platelet aggregation and blood clotting. Two negatively charged lysophospholipids, LPA and lysophosphatidylserine, specifically inhibited the binding of β2 -GPI to oxidized LDL in a concentration-dependent manner. Intrinsic tryptophan fluorescence studies demonstrated that emission intensity of β2 -GPI decreases in an LPA-concentration-dependent manner without a shift in wavelength maxima. LPA specifically induced the aggregation of β2 -GPI in phosphate-buffered saline, and in incubated plasma and serum, both of which are known to accumulate LPA by the action of lecithin-cholesterol acyltransferase and lysophospholipase D/autotaxin. β2 -GPI aggregated by LPA did not inhibit activated von Willebrand factor-induced aggregation, and did not prolong the activated partial thromboplastin time in blood plasma, in contrast to non-aggregated β2 -GPI. These results suggest that β2 -GPI aggregated by the binding to LPA fails to inhibit platelet aggregation and blood clotting in contrast to non-aggregated β2 -GPI.