IMMUNOPATHOLOGIC STUDIES OF HEYMANN NEPHRITIS

Heymann肾炎是一种膜性肾病的大鼠模型。 肾小管上皮细胞粗制制剂的单次免疫 抗原。对这种模型的免疫致病机制的研究表明 几种抗原-抗体系统有助于形成 上皮下免疫沉积。其中两个抗原-抗体系统 具有特殊的相互关系，因为抗原和它们各自的 抗体和抗独特型抗体通过 往复式的内部图像。抗独特型药物的研究进展 模拟抗原(AG1)的抗体(AB2)增强持续合成 属于AB1。 AG1是一种与肾小球抗原(AG2)结合的小管抗原。AG2 (GEC-gp140)是一种碱性(等电点9.2)的膜蛋白，是 肾小球上皮细胞，脱落到鲍曼氏间隙，可以 在尿液中检测到。当灌流到孤立的近端肾小管时， 初步数据显示，GEC-gp140抑制近端重吸收 钠含量降低20-40%。这些观察结果提出了以下假设： 假设：1)这些抗原-抗体系统的独特特征 有助于Heymann肾炎的免疫发病机制。2)GEC-gp140 是由肾小球上皮细胞合成和分泌成 鲍曼氏间隙，通过它进入管腔，结合到 近端肾小管膜和改变肾小管对钠的重吸收。 目的1：GEC-gp140的生化特性，包括氨基酸 翻译后氨基酸序列的测定与分析 使用生物合成标记技术的修饰。 目的2：测定GEC-gp140合成的调节； 体内，使用肾小球损伤的动物模型，并在体外，使用 培养中的肾小球上皮细胞。 目的3：证实GEC-gp140对肾小管的影响 功能，通过重复小管灌注研究。 从这些研究中获得的数据将提供正常情况的知识 这些作为抗原参与的蛋白质的生理功能 Heymann肾炎的免疫发病机制。

Heymann nephritis is a rat model of membranous nephropathy induced by a single immunization with a crude preparation of renal tubular epithelial antigens. Studies of the immunopathogenesis of this model have shown that several antigen-antibody systems contribute to the formation of subepithelial immune deposits. Two of these antigen-antibody systems have a special inter-relationship, as the antigens and their respective antibodies and anti-idiotypic antibodies bind to each other through reciprocating internal images. The development of anti-idiotypic antibodies (Ab2) which mimic antigen (Ag1) augment continued synthesis of Ab1. Ag1 is a tubular antigen that binds to a glomerular antigen (Ag2). Ag2 (gec-gp140) is a basic (pI 9.2) membrane protein unique to the glomerular epithelial cell, is shed into Bowmans space and can be detected in urine. When perfused into isolated proximal renal tubules, preliminary data show that gec-gp140 inhibits proximal reabsorption of sodium by 20-40%. These observations suggest the following hypothesis: Hypothesis: 1) The unique features of these antigen-antibody systems contribute to the immunopathogenesis of Heymann nephritis. 2) gec-gp140 is synthesized and secreted by the glomerular epithelial cell into Bowmans space, whereby it enters the tubular lumen, binds to the proximal tubular membrane and alters tubular reabsorption of sodium. Objective 1: Biochemical characterization of gec-gp140, including amino acids sequence determination and analysis of post-translational modifications using biosynthetic labelling techniques. Objective 2: Determination of regulation of synthesis of gec-gp140; in vivo, using animal models of glomerular injury, and in vitro, using glomerular epithelial cells in culture. Objective 3: Confirmation of the influence of gec-gp140 on tubular function, by repetition of tubule perfusion studies. Data obtained from these studies will provide knowledge of the normal physiologic function of these proteins which participate as antigens in the immunopathogenesis of Heymann nephritis.