beta(2)-Glycoprotein I promotes the binding of anionic phospholipid vesicles by macrophages

beta(2)-Glycoprotein I is a single-chain 50-kDa protein that circulates in plasma at a concentration of approximate to 200 mu g/mL. Its physiological role remains uncertain, but an important clue is the frequent presence of a ntibodies to this protein in patients with recurrent thrombosis, We have is olated beta(2)-glycoprotein I and examined its effect on the binding of pho sphatidylserine (PS) vesicles by human monocyte-derived macrophages and by phorbol ester-stimulated THP-1 cells. beta(2)-Glycoprotein I stimulated the binding of PS vesicles by these cells in a concentration-dependent manner. Vesicles containing other anionic phospholipids, such as cardiolipin, phos phatidic acid, or cardiolipin, inhibited the binding, whereas PC vesicles h ad no effect. Platelet-derived microvesicles, which contain anionic phospho lipid on the outer leaflet of their phospholipid bilayer, also inhibited be ta(2)-glycoprotein I-dependent binding of anionic phospholipid vesicles. Th e binding is associated with incorporation of phospholipid in the cell memb rane and internalization of beta(2)-glycoprotein I. These findings suggest a physiological function for beta(2)-glycoprotein I in the clearance of pro coagulant anionic phospholipid-containing cell surfaces from the circulatio n.