Immunopathologic Study on The Pathogenesis of Glomerulonephritis

该项目的目的是研究免疫性肾小球损伤的机制，特别是研究抗体与种植在肾小球内皮(GEN)上的抗原相互作用后发生的事件。为此，通过隔离肾脏灌流技术将凝集素植入GEN，然后对灌流的肾脏进行再血管化。静脉注射抗凝集素抗体诱导急性肾小球肾炎。对于HPA，抗体阳性接种后立即在Gen上形成颗粒状的HPA-抗-HPA免疫沉积(ID)，其机制涉及细胞骨架的修补/脱落。这些IDs从肾小球毛细血管壁的管腔向上皮下区移动，这表明在该模型中可诱导膜样病变。此外，还从大鼠肾小球细胞质膜上纯化了HPA结合糖蛋白。兔抗这种蛋白的抗体与足细胞的游离面发生特异性反应，其表位的性质(S)被认为与理解某种人类肾小球肾炎有关。

The aim of the project was to study the mechanisms of immune glomerular injury, particularly to study the events following the interaction of antibodies with antigen planted on the glomerular endothelium (GEN). For this purpose, a lectin was implanted on the GEN by isolated kidney perfusion technique and subsequent re-vascularization of perfused kidney. Acute glomerulonephritis was induced by the intravenous administration of anti-lectin antibodies. In case of HPA, granular HPA-anti-HPA immune deposits (IDs) were formed on the GEN immediately after antibody administration possively through the mechanisms of patching/shedding involving cytoskeleton. These IDs moved from the luminal aspect of the glomerular capillary wall to the subepithelial area suggesting that membranous-like lesion was inducible in this model. In addition, HPA-binding glycoprotein was purified from the plasma membrane of rat glomerular cells. Rabbit antibodies to this protein reacted specifically with the free surface of podocytes and the nature of the epitope(s) was thought to be pertinent to the understanding of some kind of human glomerulonephritis.