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Journal of Lipid Research, Vol. 42, 697-709, May 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

A specific ligand for ß₂-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages

Correspondence to: Eiji Matsuura, To whom correspondence should be addressed., eijimatu{at}md.okayama-u.ac.jp (E-mail)

ß₂-Glycoprotein I (ß₂-GPI) is a major antigen for antiphospholipid antibodies (Abs) present in patients with the antiphospholipid syndrome (APS). We previously reported that ß₂-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 ß₂-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 ß₂-GPI and subsequently by anti-ß₂-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 ß₂-GPI and an anti-ß₂-GPI auto-Ab (WB-CAL-1), derived from (NZW x BXSB) F1 mouse, an animal APS model. Anti-ß₂-GPI auto-Abs derived from APS patients with episodes of arterial thrombosis were detected in ELISA, using a solid phase oxLig-1 complexed with ß₂-GPI.

We suggest that autoimmune atherogenesis linked to ß₂-GPI interaction with oxLDL and Abs may be present in APS.—Kobayashi K., E. Matsuura, Q. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Voelker, and T. Koike. A specific ligand for ß₂-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J. Lipid Res. 2001. 42: 697–709.

Supplementary key words: autoantibody, antiphospholipid syndrome, cholesteryl ester, macrophage

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