RRC ID 61219
Author Kobayashi K, Matsuura E, Liu Q, Furukawa J, Kaihara K, Inagaki J, Atsumi T, Sakairi N, Yasuda T, Voelker DR, Koike T.
Title A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages.
Journal J Lipid Res
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.
Volume 42(5)
Pages 697-709
Published 2001-5-1
PII S0022-2275(20)31631-X
PMID 11352976
MeSH Animals Antiphospholipid Syndrome / complications* Antiphospholipid Syndrome / physiopathology Arteriosclerosis / etiology Arteriosclerosis / immunology Autoantibodies / immunology Autoantibodies / metabolism* Cell Line Endocytosis / physiology Enzyme-Linked Immunosorbent Assay Glycoproteins / immunology Glycoproteins / metabolism* Humans Ligands Lipoproteins, LDL / chemistry Lipoproteins, LDL / immunology Lipoproteins, LDL / metabolism* Liposomes / chemistry Liposomes / metabolism Macrophages / metabolism* Magnetic Resonance Spectroscopy Methylation Mice Molecular Structure Phospholipids / metabolism Thrombosis / etiology Thrombosis / immunology beta 2-Glycoprotein I
IF 4.483
Resource
Human and Animal Cells J774.1(RCB0434)