A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages.
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.
Kobayashi
K
K
Department of Cell Chemistry, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama 700-8558, Japan.
Matsuura
E
E
Liu
Q
Q
Furukawa
J
J
Kaihara
K
K
Inagaki
J
J
Atsumi
T
T
Sakairi
N
N
Yasuda
T
T
Voelker
D R
DR
Koike
T
T
D000818:Animals; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000503:physiopathology; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D010743:Phospholipids / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology / Q000276:immunology; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D008024:Ligands; D008077:Lipoproteins, LDL; D008081:Liposomes; D010743:Phospholipids; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein