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Analysis of the Mechanism of Renal Injury by Application of Monoclonal Antibodies.

应用单克隆抗体分析肾损伤机制。

基本信息

批准号：
01480163
负责人：
SHIMIZU Fujio
金额：
$ 4.48万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

The purpose of this study is to analyze the mechanism of renal injury at the molecular level by application of monoclonal antibody (MA). We have produced 2 kinds of MAs which induce a massive proteinuria in rats by a single intravenous injection. MA 5-1-6, IgG1, binds to the surface of glomerular epithelial foot processes, mainly to slit diaphragm MA 1-22-3, IgG3, binds to the limited surface of mesangial cells facing endothelial cells. The minimum dose of both MAs required to induce proteinuria is very small in comparison with already reported one in several kinds of experimental glomerulonephritides. This also indicates that each epitope recognized by both MAs is a very limited point which plays the critical role in keeping the normal glomerular permeability.The study of our MAs indicates that a chain reaction leading to proteinuria with or without mesangial lesions is initiated by the reaction between 2 defined molecules (MA and very specific surface molecules of glomerular cells). In the case of MA 5-1-6 the proteinuria is induced without the involvement of the classical mediators of immune injury such as complement or leukocytes.We have demonstrated that glomerular cell injury depends on an epitope specific interaction between a cell surface epitope as a receptor and a MA as a ligand. This seems to be an entirely new mechanism by which proteinuria can be induced. The simplicity of MA-induced in vivo models is ideal for analyzing the immunopathology of induced lesions at molecular levels.

本研究的目的是应用单抗从分子水平分析肾损伤的发生机制。我们生产了两种单次静脉注射可引起大鼠大量蛋白尿的单胺类化合物。MA5-1-6，IgG1，主要结合于肾小球上皮足突表面，主要与裂孔隔膜MA1-22-3，IgG3，结合于系膜细胞面向内皮细胞的有限表面。与已报道的几种实验性肾小球肾炎中的一种相比，诱导蛋白尿所需的两种MA的最小剂量非常小。这也表明，两个MA识别的每个表位都是一个非常有限的点，在保持正常的肾小球通透性方面起着关键作用。我们的MA研究表明，导致蛋白尿的连锁反应是由两个定义的分子(MA和非常特定的肾小球细胞表面分子)之间的反应启动的。在MA5-1-6的情况下，蛋白尿是在没有补体或白细胞等经典免疫损伤介质参与的情况下诱导的。我们已经证明，肾小球细胞损伤依赖于作为受体的细胞表面表位与作为配基的MA之间的表位特异性相互作用。这似乎是一种导致蛋白尿的全新机制。MA诱导的体内模型的简单性是在分子水平上分析诱导损伤的免疫病理学的理想方法。