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Analysis of crescent formation by monoclonal antibody at rapidly progressive glomerulonephritis.

单克隆抗体对快速进展性肾小球肾炎新月体形成的分析。

基本信息

批准号：
10670197
负责人：
ORIKASA Michiaki
金额：
$ 1.92万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

The origin of crescent forming cells in crescentic glomerulonephritis has not been clarified in spite of the application of monoclonal antibodies (mAbs) against glomerular epithelial cells or monocytes/macrophages. This study was undertaken to characterize the cellular composition of crescent using a new marker, mAb OS-3, produced against macrophagic cells into which podocytes changed in normal rat glomerular culture. mAb OS-3 was confirmed to be reactive with some normal epithelial cells of Bowman's capsule. Three female WKY rats were injected with rabbit anti-glomerular basement membrane (GBM) serum and sacrificed, respectively at 2 hours, 1, 3, 7, 14 days and 2 months. mAb OS-3-positive cells were segmentally observed at 3 days in glomeruli, increased at 14 days, but decreased at 2 month. These mAb positive cells were corresponded to cellular crescents in serially paired light microscopy on day 3 and 14. These lacked the reactivity with anti-podocalyxin in double immunofluorescence (IF) staining. Immunoelectron microscopy of a glomerulus on day 3 and 7, however, reaction products were observed within cells, located on outer surface of GBM, which were considered to be podocyte based on its localization.In conclusion, we have shown a possibility that damaged podocytes partly constitute crescent forming cells with phenotypic changes visualized by positive staining with mAb OS-3, proposing a novel concept of crescent formation. That is, crescent may be partly composed of phenotypically changed cells, which could not be detected by typical markers for glomerular epithelial cells or monocytes/macrophages.

尽管应用了针对肾小球上皮细胞或单核/巨噬细胞的单克隆抗体（mab），但月牙形肾小球肾炎中月牙形细胞的起源尚未明确。本研究使用一种新的标记物mAb OS-3来表征crescent的细胞组成，mAb OS-3是针对巨噬细胞产生的，巨噬细胞在正常大鼠肾小球培养中发生足细胞变化。证实OS-3单抗对部分正常鲍曼囊上皮细胞有反应。3只雌性WKY大鼠分别于2小时、1、3、7、14天和2个月时注射兔抗肾小球基底膜（GBM）血清处死。mAb os -3阳性细胞在肾小球内3天呈节段性变化，14天呈增加，2个月呈下降。这些单克隆抗体阳性细胞在第3天和第14天的连续配对光镜下对应于细胞新月形。双免疫荧光（IF）染色对抗足霉素缺乏反应性。然而，第3天和第7天的肾小球免疫电镜观察到，反应产物在细胞内，位于GBM的外表面，根据其定位认为是足细胞。总之，我们已经证明了一种可能性，即受损足细胞部分构成新月形成细胞，其表型变化通过单抗OS-3阳性染色可见，提出了新月形成的新概念。也就是说，新月可能部分由表型改变的细胞组成，这是肾小球上皮细胞或单核/巨噬细胞的典型标记所无法检测到的。