β2-Glycoprotein I promotes the binding of anionic phospholipid vesicles by macrophages

Abstract

β2-Glycoprotein I is a single-chain 50-kDa protein that circulates in plasma at a concentration of ≃200 μg/mL. Its physiological role remains uncertain, but an important clue is the frequent presence of antibodies to this protein in patients with recurrent thrombosis. We have isolated β2- glycoprotein I and examined its effect on the binding of phosphatidylserine (PS) vesicles by human monocyte-derived macrophages and by phorbol ester- stimulated THP-1 cells. β2-Glycoprotein I stimulated the binding of PS vesicles by these cells in a concentration-dependent manner. Vesicles containing other anionic phospholipids, such as cardiolipin, phosphatidic acid, or cardiolipin, inhibited the binding, whereas PC vesicles had no effect. Platelet-derived microvesicles, which contain anionic phospholipid on the outer leaflet of their phospholipid bilayer, also inhibited β2- glycoprotein I-dependent binding of anionic phospholipid vesicles. The binding is associated with incorporation of phospholipid in the cell membrane and internalization of β2-glycoprotein I. These findings suggest a physiological function for β2-glycoprotein I in the clearance of procoagulant anionic phospholipid-containing cell surfaces from the circulation.