Induction of proteinuria in the rat by a monoclonal antibody against SGP-115/107.
Induction of proteinuria in the rat by a monoclonal antibody against SGP-115/107.
复制标题
通过抗 SGP-115/107 的单克隆抗体诱导大鼠出现蛋白尿。
DOI：
10.1038/ki.1988.73
复制
发表时间：
1988
影响因子：
19.6
通讯作者：
Rennke,HG
中科院分区：
文献类型：
--
作者：
Mendrick,DL;Rennke,HG
I.通过针对SGP-115/107的单克隆抗体在大鼠中诱导蛋白尿。目前，个体抗原决定簇在抗体介导的肾小球损伤的发病机制中的作用尚不完全清楚。本研究旨在比较单克隆抗体与肾小球毛细血管壁中存在的三种不同抗原决定簇结合的效果。测试了十种单克隆抗体在大鼠中的肾毒性能力。六种针对基底膜层粘连蛋白的抗体和三种对内皮和肾小球内脏上皮细胞表面上存在的129/117 kd抗原复合物具有特异性的抗体不会诱导蛋白尿或结构损伤。一种非补体结合单克隆抗体，可免疫沉淀来自肾小球细胞膜制剂的 115/107 kd 唾液酸糖蛋白 (SGP-115/107) 和来自近端肾小管、肠细胞和肝细胞的 107 kd 成分，诱导肾小球上皮细胞改变，包括足突结构的局灶性消失、细胞质中的空泡变化、细胞的微绒毛转化足细胞的表面和局灶性回缩，导致上皮与下面的基底膜分离。仅在给予抗体时给予完全弗氏佐剂的动物中，这些结构变化才会伴随立即短暂的蛋白尿。这些研究表明，通过给予细胞相关抗原特异性的单克隆抗体，可以在大鼠中诱导直接抗体介导的肾小球损伤。
I. Induction of proteinuria in the rat by a monoclonal antibody against SGP-115/107. The role of individual antigenic determinants in the pathogenesis of antibody-mediated glomerular injury is, at present, incompletely understood. This study was designed to compare the effect of monoclonal antibodies upon binding to three distinct antigenic determinants present in the glomerular capillary wall. Ten monoclonal antibodies were tested for their nephrotoxic capacity in the rat. Six antibodies directed against basement membrane laminin and three antibodies with specificity for a 129/117 kd antigenic complex present on endothelial and glomerular visceral epithelial cell surfaces did not induce proteinuria or structural injury. A non-complement binding monoclonal antibody that immunoprecipitates a 115/107 kd sialo-glyco-protein (SGP-115/107) from glomerular cell membrane preparations and a 107 kd component from proximal tubules, intestinal cells and liver cells, induces glomerular epithelial cell alterations consisting of focal obliteration of foot process architecture, vacuolar changes in the cytoplasm, microvillous transformation of the cell surface, and focal retraction of podocytes, resulting in detachment of the epithelium from the underlying basement membrane. These structural changes are accompanied by immediate transient proteinuria only in animals given complete Freund's adjuvant at the time of antibody administration. These studies indicate that direct antibody-mediated glomerular injury can be induced in the rat by administration of monoclonal antibodies specific for cell associated antigens.