論文 - 詳細
| RRC ID | 1185 |
|---|---|
| 著者 | Liu Q, Kobayashi K, Furukawa J, Inagaki J, Sakairi N, Iwado A, Yasuda T, Koike T, Voelker DR, Matsuura E. |
| タイトル | Omega-carboxyl variants of 7-ketocholesteryl esters are ligands for beta(2)-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages. |
| ジャーナル | J Lipid Res |
| Abstract |
beta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We recently reported that beta(2)-GPI specifically binds to oxidized LDL (oxLDL) and that the beta(2)-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9-carboxynonanoate (Kobayashi, K., E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Voelker, and T. Koike. 2001. A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J. Lipid Res. 42: 697-709). In the present study, we demonstrate that omega-carboxylated 7-ketocholesteryl esters are critical for beta(2)-GPI binding. A positive ion mass spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383 and 441 in the presence of acetone, which share features of oxLig-1 and 7-ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto) dodecanoate. These ligands were recognized by beta(2)-GPI. Liposome binding to macrophages was significantly increased depending on the ligand's concentration, in the presence of beta(2)-GPI and an anti-beta(2)-GPI Ab. Synthesized variant, 7-ketocholesteryl-13-carboxytridecanoate (13-COOH-7KC), also showed a significant interaction with beta(2)-GPI and a similar binding profile with macrophages. Methylation of the carboxyl function diminished all of the specific ligand interactions with beta(2)-GPI. Thus, omega-carboxyl variants of 7-ketocholesteryl esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL. |
| 巻・号 | 43(9) |
| ページ | 1486-95 |
| 公開日 | 2002-9-1 |
| DOI | 10.1194/jlr.m20063-jlr200 |
| PII | S0022-2275(20)32813-3 |
| PMID | 12235181 |
| MeSH | Antibodies / immunology* Cholesterol Esters / metabolism* Chromatography, High Pressure Liquid Glycoproteins / metabolism* Humans Ketocholesterols / metabolism* Ligands Lipoproteins, LDL / metabolism* Liposomes / metabolism Macrophages / immunology Macrophages / metabolism* Molecular Structure Oxidation-Reduction Protein Binding beta 2-Glycoprotein I |
| IF | 4.483 |
| 引用数 | 53 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | J774.1(RCB0434) |