Boyd H C, Gown A M, Wolfbauer G, Chait A
Department of Pathology, University of Washington, Seattle 98195.
Am J Pathol. 1989 Nov;135(5):815-25.
Low density lipoproteins (LDL) that have been oxidatively modified have been implicated in the pathogenesis of atherosclerosis. Monoclonal antibodies were generated against oxidatively modified human low density lipoproteins (OxLDL); these antibodies reacted with OxLDL, but did not react with native LDL, either in an enzyme-linked immunosorbent assay (ELISA) or a Western blot analysis. The anti-OxLDL antibodies did react with other modified forms of LDL (eg, acetylated LDL, malondialdehyde-modified LDL, and cell-modified LDL) that were recognized by the scavenger receptor on macrophages. Single- and double-label immunofluorescence of atheromatous lesions from a Watanabe heritable hyperlipidemic (WHHL) rabbit demonstrated some colocalization of proteins detected by anti-LDL and anti-OxLDL antibodies. However, clearly there were also areas stained by the anti-OxLDL antibodies that did not stain with anti-LDL. Staining of the lesion by the anti-OxLDL antibody was abolished by adsorption of the antibody with OxLDL, but not by adsorption with LDL or bovine serum albumin. Arterial tissue from a control New Zealand White rabbit did not show staining with anti-LDL or anti-OxLDL antibodies. These observations suggest that OxLDL (or possibly other proteins recognized by the anti-OxLDL antibody) is present in atheromatous lesions of WHHL rabbits, and are consistent with oxidatively modified lipoproteins having a role in atherogenesis.
氧化修饰的低密度脂蛋白（LDL）与动脉粥样硬化的发病机制有关。制备了针对氧化修饰的人低密度脂蛋白（OxLDL）的单克隆抗体；在酶联免疫吸附测定（ELISA）或蛋白质印迹分析中，这些抗体与OxLDL反应，但不与天然LDL反应。抗OxLDL抗体确实与其他修饰形式的LDL（例如乙酰化LDL、丙二醛修饰的LDL和细胞修饰的LDL）反应，这些修饰形式的LDL可被巨噬细胞上的清道夫受体识别。对一只渡边遗传性高脂血症（WHHL）兔的动脉粥样硬化病变进行单标记和双标记免疫荧光检测，结果显示抗LDL和抗OxLDL抗体检测到的蛋白质有一些共定位。然而，显然也有一些区域被抗OxLDL抗体染色，但未被抗LDL抗体染色。用OxLDL吸附抗体可消除抗OxLDL抗体对病变的染色，但用LDL或牛血清白蛋白吸附则不能。对照新西兰白兔的动脉组织未显示抗LDL或抗OxLDL抗体染色。这些观察结果表明，OxLDL（或可能是抗OxLDL抗体识别的其他蛋白质）存在于WHHL兔的动脉粥样硬化病变中，并且与氧化修饰的脂蛋白在动脉粥样硬化发生中起作用一致。
