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

本研究的目的是应用单克隆抗体从分子水平分析肾损伤的机制。我们制备了两种单次静脉注射引起大鼠大量蛋白尿的MA。MA 5-1-6，IgG 1，结合于肾小球上皮足突表面，主要结合于裂隔膜MA 1-22-3，IgG 3，结合于肾小球系膜细胞面向内皮细胞的有限表面。诱导蛋白尿所需的两种MA的最小剂量与已经报道的几种实验性肾小球肾炎中的一种相比非常小。这也表明，每个表位识别的两个MA是一个非常有限的点，发挥关键作用，在保持正常的肾小球通透性。我们的MA的研究表明，导致蛋白尿伴或不伴系膜病变的连锁反应是由2个定义的分子（MA和肾小球细胞的非常特异的表面分子）之间的反应启动。在MA 5-1-6的情况下，蛋白尿是在没有经典的免疫损伤介质如补体或白细胞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和作为配体的MA之间的表位特异性相互作用。这似乎是一个全新的机制，蛋白尿可以诱导。MA诱导的体内模型的简单性对于在分子水平上分析诱导的病变的免疫病理学是理想的。

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.