- 日本アフェレシス学会雑誌 (ISSN:13405888)
- vol.23, no.2, pp.167-175, 2004-05-31
Oxidative stress is thought to be etiologically related to atherosclerosis. Experimental evidence clearly demonstrates the presence of oxidized LDL (oxLDL) in the intima of arteries and that it contributes to the initiation and progression of atherosclerotic lesions. We have recently demonstrated that oxLDL interacts with β2-glycoprotein I (β2-GPI) to form complexes and that these complexes circulate in the blood stream of patients not only with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) but also with other systemic inflammatory diseases. Our in vitro experiments showed that oxLDL quickly interacts with β2-GPI via specific ligands generated by oxidation, in which the negative charge of oxLDL is neutralized by the complex formed. It was also shown that β2-GPI/oxLDL complexes are taken up by macrophages via lgG anti-β2-GPI autoantibody-mediated phagocytosis. Thus, IgG immune complexes with oxLDL and β2-GPI are thought to be atherogenic and β2-GPI/oxLDL complexes maybe implicated as autoantigens relevant in autoimmune-mediated atherogenesis in APS patients. In contrast, a set of reports indicated that natural antibodies (mainly of the IgM class) derived from hyperlipidemic mice reduced the incidence of atherosclerosis in experimental models. Further study should elucidate whether IgG and/or IgM antibodies induced to oxLDL and β2-GPI/oxLDL complexes in APS are pathogenic or protective, or are an epiphenomenon in the development of arterial thrombosis.