Immune clearance of phosphatidylserine-expressing cells by phagocytes: The role of β₂-glycoprotein I in macrophage recognition

The function of β₂-glycoprotein I (β₂GPI), a 50-kDa serum glycoprotein, is not completely understood but has been suggested to be involved in the regulation of thrombosis (Brighton, T. A., Hogg, P. J., Dai, Y.-P., Murray, B. H., Choing, B. H., and Chesterman, C. N. (1996) Br. J. Haematol. 93, 185-194) and the clearance of phosphatidylserine (PS)- expressing cells (Chonn, A., Semple S.C., and Cullis P. R. (1995) J. Biol. Chem. 270, 25845-25849). To further understand the role of this protein, we characterized the ability of β₂GPI to interact with PS vesicles and influence their uptake by macrophages in vitro. β₂GPI bound to and precipitated vesicles containing anionic but not zwitterionic phospholipids in a gel diffusion assay. β₂GPI also inhibited the procoagulant activity of PS liposomes. In vitro phagocytosis studies showed 20-fold greater uptake of PS liposomes over phosphatidylcholine liposomes. This enhanced uptake was maintained even after PS was 'shielded' with β₂GPI and further increased upon the addition of β₂GPI antibodies. Similar to liposomes, PS-expressing apoptotic thymocytes and lipid symmetric red blood cell ghosts bowed β₂GPI. Macrophage uptake of these cells was also maintained or enhanced in the presence of β₂GPI and further increased upon the addition of β₂GPI antibodies. It is concluded that β₂GPI can play a critical role in hemostasis by influencing both thrombosis and the clearance of PS-expressing cells.