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

Kazuko Kobayashi, Eiji Matsuura, Qingping Liu, Jun Ichi Furukawa, Keiko Kaihara, Junko Inagaki, Tatsuya Atsumi, Nobuo Sakairi, Tatsuji Yasuda, Dennis R. Voelker, Takao Koike

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Abstract

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.

Original languageEnglish
Pages (from-to)697-709
Number of pages13
JournalJournal of Lipid Research
Volume42
Issue number5
Publication statusPublished - Jun 15 2001

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Keywords

  • Antiphospholipid syndrome
  • Autoantibody
  • Cholesteryl ester
  • Macrophage

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Kobayashi, K., Matsuura, E., Liu, Q., Furukawa, J. I., Kaihara, K., Inagaki, J., Atsumi, T., Sakairi, N., Yasuda, T., Voelker, D. R., & Koike, T. (2001). A specific ligand for β2-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. Journal of Lipid Research, 42(5), 697-709.