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 approximately 200 microg/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 beta(2)-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. 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, 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 beta(2)-glycoprotein I-dependent binding of anionic phospholipid vesicles. The binding is associated with incorporation of phospholipid in the cell membrane and internalization of beta(2)-glycoprotein I. These findings suggest a physiological function for beta(2)-glycoprotein I in the clearance of procoagulant anionic phospholipid-containing cell surfaces from the circulation.
Thiagarajan
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Division of Hematology, Department of Internal Medicine, University of Texas Health Sciences Center, Houston 77030, USA. perumal@heart.med.uth.tmc.edu
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Benedict
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D000838:Anions / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D014316:Tritium; D053482:beta 2-Glycoprotein I
D000838:Anions; D002308:Cardiolipins; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I; D014316:Tritium; D002784:Cholesterol