Mendrick D L, Rennke H G
J Immunol. 1986 Sep 1;137(5):1517-26.
We describe a unique mesangial matrix component of the rat glomerulus identified by a murine monoclonal antibody. The antigen is present exclusively in the glomerular mesangium and cannot be detected in other rat tissues by indirect immunofluorescence techniques or following pretreatment of tissue sections with acid urea or other nonionic detergents. Specific immunoprecipitation of the solubilized antigen yields a single peptide with an apparent m.w. of 81,000 when analyzed by discontinuous SDS-PAGE. This mesangial matrix component is collagenase resistant and trypsin sensitive. Perfusion of an isolated kidney preparation with this antibody results in direct binding of the mouse immunoglobulin to its mesangial antigen. Passive administration of the monoclonal antibody to Lewis rats results in characteristic electron dense deposits within the mesangial matrix that can be visualized ultrastructurally as early as 3 days. The immune deposits form without the activation of rat complement and persist for longer periods than those that develop after the planting of aggregated proteins or preformed immune complexes. Experimental animals that received either a monoclonal antibody specific for laminin or a non-kidney binding preparation did not develop such immune deposits at any time during the course of the autologous phase of the immune process. The results obtained in this study indicate that electron dense immune deposits can develop in the mesangium with the participation of a unique intrinsic matrix component and specific circulating monoclonal antibodies by an in situ mechanism of immune complex formation.
我们描述了一种由鼠单克隆抗体识别的大鼠肾小球独特的系膜基质成分。该抗原仅存在于肾小球系膜中,通过间接免疫荧光技术或在用酸性尿素或其他非离子去污剂预处理组织切片后,在其他大鼠组织中无法检测到。对溶解抗原进行特异性免疫沉淀,通过不连续SDS-PAGE分析,产生一种表观分子量为81,000的单一肽段。这种系膜基质成分对胶原酶有抗性,对胰蛋白酶敏感。用该抗体灌注离体肾脏制剂会导致小鼠免疫球蛋白直接与其系膜抗原结合。将单克隆抗体被动给予Lewis大鼠会导致系膜基质内出现特征性电子致密沉积物,最早在3天即可通过超微结构观察到。免疫沉积物的形成无需激活大鼠补体,并且比聚集蛋白或预先形成的免疫复合物植入后形成的沉积物持续时间更长。在免疫过程的自身阶段,接受层粘连蛋白特异性单克隆抗体或非肾脏结合制剂的实验动物在任何时候都不会出现这种免疫沉积物。本研究获得的结果表明,通过免疫复合物形成的原位机制,在一种独特的内源性基质成分和特异性循环单克隆抗体的参与下,系膜中可形成电子致密免疫沉积物。