Back to Search
Start Over
A specific ligand for β2-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages
- Source :
- Journal of Lipid Research, Vol 42, Iss 5, Pp 697-709 (2001)
- Publication Year :
- 2001
- Publisher :
- Elsevier, 2001.
-
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.
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 42
- Issue :
- 5
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Lipid Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0b3e54d6ff714328a2ee9b43cb8aa437
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/S0022-2275(20)31631-X