A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages

beta (2)-Glycoprotein I (beta (2)-GPI) is a major antigen for antiphospholi pid antibodies (Abs) present in patients with the antiphospholipid syndrome (APS), We previously reported that beta (2)-GPI specifically binds to oxid ized low density lipoprotein (oxLDL), but not to native low density lipopro tein (LDL), In the present study, a ligand specific for beta (2)- GPI, oxLi g-1, was purified from the extracted lipids of oxLDL, The structure of oxLi g-1 was sho cvn to be identical to that of synthesized 7-keto cholesteryl-9 -carboxynonanoate by mass spectroscopy and nuclear magnetic resonance analy ses. Both purified and synthesized oxLig-1 were recognized by beta (2)-GPI and subsequently by anti-BP-GPI auto-Abs, either in enzyme-linked immunosor bent assay (ELISA) or in ligand blot analysis. Binding of liposomes contain ing oxLig-1 (oxLig-1-liposomes) to mouse macrophages, J774A.1 cells, was re latively low, as compared with that of phosphatidylserine (PS)-liposomes. I n contrast, binding of oxLig-1-liposomes was enhanced more than 10-fold in the presence of both beta2-GPI and an anti-beta (2)-GPI auto-Ab (WB-CAL-1), derived from (NZW x BXSB) F1 mouse, an animal APS model, Anti-PP-GPI auto- Abs derived from APS patients with episodes of arterial thrombosis were det ected in ELISA, using a solid phase oxLig-1 complexed with beta (2)-GPI.j/r We suggest that autoimmune atherogenesis linked to PP-GPI interaction with oxLDL and Abs may be present in APS.-Kobayashi Ii, E. Matsuura, Q. Liu, J. Furukawa, It. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Voelker, and T. Koike. A specific ligand for beta (2)-glycoprotein I media tes autoantibody-dependent uptake of oxidized low density lipoprotein by ma crophages.