Sugiyama N, Marcovina S, Gown A M, Seftel H, Joffe B, Chait A
Department of Medicine, University of Washington, Seattle 98195.
Am J Pathol. 1992 Jul;141(1):99-106.
Human xanthomas derived from four subjects with familial hypercholesterolemia (3 homozygotes and 1 heterozygote) were studied by immunohistochemical methods to determine the presence and distribution of lipoproteins, which have been implicated in the pathogenesis of atherosclerosis. Oxidatively modified low-density lipoprotein (OxLDL) epitopes detected with anti-OxLDL monoclonal antibodies, appeared to have a similar distribution in xanthomata to that of macrophages, detected by a cell-specific monoclonal antibody. Double antibody labeling with both an anti-macrophage antibody and an anti-OxLDL antibody demonstrated that OxLDL epitopes are associated with macrophages and occurred intracellularly. Low-density lipoprotein (LDL) epitopes were detected extracellularly, with a distribution that was different from that of OxLDL. In addition, apo(a) epitopes detected by an apo(a) specific monoclonal antibody, had a distribution similar to that of LDL in the dermis and subcutaneous tissues. The observed epitope distribution of LDL, OxLDL, or apo(a) was the same regardless of the method of treatment of the patients from whom the xanthomas were obtained (probucol, simvastatin, LDL apheresis). These findings suggest that OxLDL is likely to play a pathogenetic role in the lipid accumulation by macrophages in xanthomas, and suggest that Lp(a) also may play a role in their pathogenesis.
通过免疫组织化学方法研究了来自4例家族性高胆固醇血症患者（3例纯合子和1例杂合子）的人类黄瘤，以确定与动脉粥样硬化发病机制相关的脂蛋白的存在和分布。用抗氧化修饰低密度脂蛋白（OxLDL）单克隆抗体检测到的氧化修饰低密度脂蛋白表位，在黄瘤中的分布似乎与用细胞特异性单克隆抗体检测到的巨噬细胞相似。用抗巨噬细胞抗体和抗OxLDL抗体进行双重抗体标记表明，OxLDL表位与巨噬细胞相关且存在于细胞内。低密度脂蛋白（LDL）表位在细胞外被检测到，其分布与OxLDL不同。此外，用载脂蛋白（a）特异性单克隆抗体检测到的载脂蛋白（a）表位，在真皮和皮下组织中的分布与LDL相似。无论从获得黄瘤的患者采用何种治疗方法（普罗布考、辛伐他汀、LDL血液成分分离术），所观察到的LDL、OxLDL或载脂蛋白（a）的表位分布都是相同的。这些发现表明，OxLDL可能在黄瘤中巨噬细胞的脂质蓄积中起致病作用，并表明脂蛋白（a）也可能在其发病机制中起作用。
