Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition.
The function of beta2-glycoprotein I (beta2GPI), 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 beta2GPI to interact with PS vesicles and influence their uptake by macrophages in vitro. beta2GPI bound to and precipitated vesicles containing anionic but not zwitterionic phospholipids in a gel diffusion assay. beta2GPI 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 beta2GPI and further increased upon the addition of beta2GPI antibodies. Similar to liposomes, PS-expressing apoptotic thymocytes and lipid symmetric red blood cell ghosts bound beta2GPI. Macrophage uptake of these cells was also maintained or enhanced in the presence of beta2GPI and further increased upon the addition of beta2GPI antibodies. It is concluded that beta2GPI can play a critical role in hemostasis by influencing both thrombosis and the clearance of PS-expressing cells.
Balasubramanian
K
K
Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Chandra
J
J
Schroit
A J
AJ
D001053:Apolipoproteins / Q000502:physiology*; D017209:Apoptosis; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000502:physiology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000276:immunology*; D010743:Phospholipids / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D053482:beta 2-Glycoprotein I
D001053:Apolipoproteins; D002148:Calmodulin-Binding Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; D010743:Phospholipids; D053482:beta 2-Glycoprotein I