Antiphospholipid antibodies and atherosclerosis.
Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL) induced in patients with antiphospholipid syndrome and their antigenic epitopes are cryptic. The epitopes appear on the surface of beta2-GPI molecule only when beta2-GPI interacts with lipid membranes containing negatively charged phospholipids or polyoxygenated polystyrene surface. Our data also indicated that CuSO4-oxidized low density lipoproteins (oxLDL) are subsequently targeted by beta2-GPI and aCL; however, malonedialdehyde (MDA)-modified LDL were recognized neither by beta2-GPI nor aCL. Beta2-GPI binding to LDL was rapidly increased by incubation with CuSO4. Oxidation of lipoproteins was accompanied with the increment of thiobarbituric acid-reactive substances (TBARS) and denature of apolipoprotein. Ligands on LDL for beta2-GPI seemed to be intermediate oxidative derivatives which were extractable into the chloroform phase by Bligh and Dyer's extraction, but not MDA. Further, immune responses against beta2-GPI, as an anti-atherogenic protein, were demonstrated to induce atherogenic effect in in vitro oxLDL uptake by macrophages.
Matsuura
E
E
Department of Cell Chemistry, Institute of Cellular and Molecular Biology, Okayama University Medical School, Japan.
Kobayashi
K
K
Yasuda
T
T
Koike
T
T
D017153:Antibodies, Anticardiolipin / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications / Q000276:immunology; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000276:immunology; D008563:Membrane Lipids / Q000276:immunology; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology / Q000276:immunology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000276:immunology; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D008563:Membrane Lipids; D010743:Phospholipids; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein