A specific ligand for β2-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages

• Published in: Journal of lipid research Vol. 42; no. 5; pp. 697 - 709
• Main Authors: Kobayashi, Kazuko, Matsuura, Eiji, Liu, Qingping, Furukawa, Jun-ichi, Kaihara, Keiko, Inagaki, Junko, Atsumi, Tatsuya, Sakairi, Nobuo, Yasuda, Tatsuji, Voelker, Dennis R., Koike, Takao
• Format: Journal Article
• Language: English
• Published: Elsevier 01.05.2001
• Subjects: antiphospholipid syndrome; autoantibody; cholesteryl ester; macrophage
• ISSN: 0022-2275
• DOI: 10.1016/S0022-2275(20)31631-X

β2-Glycoprotein I (β2-GPI) is a major antigen for antiphospholipid antibodies (Abs) present in patients with the antiphospholipid syndrome (APS). We previously reported that β2-GPI specifically binds to oxidized low density lipoprotein (oxLDL), but not to native low density lipoprotein (LDL). In the present study, a ligand specific for β2-GPI, oxLig-1, was purified from the extracted lipids of oxLDL. The structure of oxLig-1 was shown to be identical to that of synthesized 7-ketocholesteryl-9-carboxynonanoate by mass spectroscopy and nuclear magnetic resonance analyses. Both purified and synthesized oxLig-1 were recognized by β2-GPI and subsequently by anti-β2-GPI auto-Abs, either in enzyme-linked immunosorbent assay (ELISA) or in ligand blot analysis. Binding of liposomes containing oxLig-1 (oxLig-1-liposomes) to mouse macrophages, J774A.1 cells, was relatively low, as compared with that of phosphatidylserine (PS)-liposomes. In contrast, binding of oxLig-1-liposomes was enhanced more than 10-fold in the presence of both β2-GPI and an anti-β2-GPI auto-Ab (WB-CAL-1), derived from (NZW x BXSB) F1 mouse, an animal APS model. Anti-β2-GPI auto-Abs derived from APS patients with episodes of arterial thrombosis were detected in ELISA, using a solid phase oxLig-1 complexed with β2-GPI.We suggest that autoimmune atherogenesis linked to β2-GPI interaction with oxLDL and Abs may be present in APS.