RABBIT AND HUMAN ATHEROSCLEROTIC LESIONS CONTAIN IGG THAT RECOGNIZES EPITOPES OF OXIDIZED LDL

Atherosclerotic lesions contain relatively large quantities of IgG. We have previously shown that both human and rabbit sera contain autoant ibodies against epitopes of oxidized (Ox) low-density lipoprotein (LDL ) and that LDL isolated from atherosclerotic lesions contains small am ounts of tightly bound IgG. However, it is not known whether IgG isola ted from atherosclerotic lesions recognizes epitopes present in native LDL or Ox-LDL. IgG was isolated from Watanabe heritable hyperlipidemi c (WHHL) rabbit atherosclerotic lesions by sequential salt extractions , purified by fast protein liquid chromatography on protein G, and use d in a solid-phase radioimmunoassay. IgG and immune complexes were als o isolated from the saline extracts of human lesions by adsorption ont o latex beads coated with anti-human IgG antibodies or protein A. IgG isolated from rabbit lesions showed significant titers against malondi aldehyde (MDA)-modified LDL and LDL oxidized by copper ions for 4 and 18 hours but not against native LDL. On Western blots, lesion IgG stai ned MDA-LDL land fragments of Ox-LDL. Western blots of immune complexe s isolated from human lesions revealed the presence in the isolated co mplexes of both apoprotein B and apoprotein B fragments, which reacted with antibodies to MDA-lysine. Furthermore, rabbit lesion IgG immunos tained epitopes of Ox-LDL present in human atherosclerotic lesions. Im munostains obtained with rabbit lesion IgG were similar to those obtai ned with a monoclonal antibody specific for MDA-lysine. The results sh ow that human and rabbit atherosclerotic lesions contain IgG that reco gnizes epitopes characteristic of Ox-LDL. These data suggest that immu nologic processes may be an important component of the atherogenic pro cess.