COMPLEMENT ACTIVATION OF THE GLOMERULER EPITHELIAL CELL

在被动型Heymann肾炎中， 肾病，抗体（抗Fx1A）激活补体的表面上， 肾小球内脏上皮细胞（GEC），以及由此产生细胞 损伤，并因此发生蛋白尿。GEC培养 含有限制补体激活的膜蛋白。很可能 这些蛋白质也存在于体内，并用于保护 GEC来自自发和抗体导向的补体激活。 有证据表明，抗Fx1A在激活 补体通过其结合并抑制GEC上的 GEC的补体调节蛋白。 为了分离这些具有补体抑制活性的蛋白质， 来自培养的大鼠GEC的膜蛋白将经受各种 色谱步骤。溶血性抗体抑制补体的能力 分析将指导这些蛋白质的分离。纯化抗体 然后将培养蛋白质并测试其抑制 调节补体，从而增强补体激活， 体外还将在体内用这些抗体进行研究， 探索补体调节在保护GEC中的作用， 在正常情况下和依赖补体的疾病中 被动型Heymann肾炎特殊补 还将分离通过抗Fx1A鉴定的调节蛋白。的 正常功能的抑制在被动Heymann中的作用 将建立肾炎。GEC的反应能力 补体激活通过增加膜表达这些 将在体外测定调节蛋白。最后，能力 的GEC，以消除抗体已结合，并抑制， 细胞表面的补体调节蛋白，将 评估。

In passive Heymann nephritis, a rat model of human membranous nephropathy, antibody (anti-Fx1A) activates complement on the surface of the glomerular visceral epithelial cell (GEC), with resultant cell injury and, consequently, the development of proteinuria. GEC in culture contain membrane proteins that limit complement activation. It is likely that these proteins are also present in vivo and serve to protect the GEC from both spontaneous and antibody-directed complement activation. Evidence exists that anti-Fx1A is particularly effective in activating complement on GEC by virtue of its binding to, and inhibiting, a complement regulatory protein of the GEC. In order to isolate these proteins with complement inhibitory activity, membrane proteins from cultured rat GEC will be subjected to various chromatographic steps. The ability to inhibit complement in a hemolytic assay will guide isolation of these proteins. Antibodies to purified proteins will then be raised and tested for their ability to inhibit the regulation of complement, thereby enhancing complement activation, in vitro. Studies will also be performed in vivo with these antibodies to explore the role complement regulation has in protecting GEC under normal circumstances and in a disease dependent upon complement activation, passive Heymann nephritis. The particular complement regulatory protein identified by anti-Fx1A will also be isolated. The role that inhibition of its normal function plays in passive Heymann nephritis will be established. The ability of the GEC to respond to complement activation by increasing membrane expression of these regulatory proteins will be determined in vitro,. Lastly, the capability of the GEC to eliminate antibody that has bound to, and inhibited, a complement regulatory protein of the surface of the cell, will be evaluated.