Exner M, Susani M, Witztum J L, Hovorka A, Curtiss L K, Spitzauer S, Kerjaschki D
Division of Ultrastructural Pathology and Cell Biology, University of Vienna, Austria.
Am J Pathol. 1996 Oct;149(4):1313-20.
Proteinuria in passive Heymann nephritis is primarily caused by reactive oxygen species that are produced by glomerular cells. Reactive oxygen species apparently exert their damaging effects on the glomerular filter by lipid peroxidation and subsequent adduct formation on matrix proteins of glomerular basement membranes. This raised the question as to the source of polyunsaturated fatty acids required as substrates for lipid peroxidation. Here we have localized by immunocytochemistry rat apolipoprotein E and apolipoprotein B within subepithelial immune deposits. Moreover, apolipoprotein B extracted from isolated glomeruli of proteinuric passive Heymann nephritis rats shows degradation and lipid peroxidation adduct formation, similar to apoproteins of oxidized lipoproteins in atherosclerotic lesions. These data provide evidence that lipoproteins accumulate within immune deposits and suggest that their lipids generate lipid-peroxidation-derived reactive compounds.
被动型海曼肾炎中的蛋白尿主要由肾小球细胞产生的活性氧所致。活性氧显然通过脂质过氧化作用以及随后在肾小球基底膜基质蛋白上形成加合物,对肾小球滤过器产生损伤作用。这就引出了关于脂质过氧化所需多不饱和脂肪酸底物来源的问题。在此,我们通过免疫细胞化学方法将大鼠载脂蛋白E和载脂蛋白B定位到了上皮下免疫沉积物中。此外,从蛋白尿被动型海曼肾炎大鼠分离出的肾小球中提取的载脂蛋白B显示出降解以及脂质过氧化加合物的形成,这与动脉粥样硬化病变中氧化脂蛋白的载脂蛋白相似。这些数据证明脂蛋白在免疫沉积物中蓄积,并提示其脂质会生成脂质过氧化衍生的反应性化合物。