1. A specific ligand for β2-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages
- Author
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Takao Koike, Dennis R. Voelker, Keiko Kaihara, Qingping Liu, Junko Inagaki, Tatsuji Yasuda, Nobuo Sakairi, Jun-ichi Furukawa, Eiji Matsuura, Kazuko Kobayashi, and Tatsuya Atsumi
- Subjects
biology ,Autoantibody ,macrophage ,QD415-436 ,Cell Biology ,Phosphatidylserine ,Biochemistry ,Blot ,chemistry.chemical_compound ,Endocrinology ,Antigen ,chemistry ,Low-density lipoprotein ,cholesteryl ester ,biology.protein ,Beta 2-Glycoprotein I ,lipids (amino acids, peptides, and proteins) ,Antibody ,Beta (finance) ,antiphospholipid syndrome ,autoantibody - Abstract
beta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for antiphospholipid antibodies (Abs) present in patients with the antiphospholipid syndrome (APS). We previously reported that beta(2)-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 beta(2)-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 beta(2)-GPI and subsequently by anti-beta(2)-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 beta(2)-GPI and an anti-beta(2)-GPI auto-Ab (WB-CAL-1), derived from (NZW x BXSB) F1 mouse, an animal APS model. Anti-beta(2)-GPI auto-Abs derived from APS patients with episodes of arterial thrombosis were detected in ELISA, using a solid phase oxLig-1 complexed with beta(2)-GPI. We suggest that autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL and Abs may be present in APS.
- Published
- 2001