Quantitative and qualitative studies of antibody-induced mesangial cell damage in the rat.
Quantitative and qualitative studies of antibody-induced mesangial cell damage in the rat.
复制标题
DOI：
10.1038/ki.1987.240
复制
发表时间：
1987-10
影响因子：
19.6
通讯作者：
Tadashi Yamamoto;Curtis B. Wilson
中科院分区：
文献类型：
--
作者：
Tadashi Yamamoto;Curtis B. Wilson
抗体致大鼠系膜细胞损伤的定量和定性研究。静脉注射异源抗大鼠胸腺细胞血清（ATS），与大鼠肾小球系膜细胞上存在的Thy-1样抗原反应，导致刘易斯大鼠的溶解性（1小时至2天）、细胞过多（4至14天）和硬化（2至3个月）系膜病变。正常对照组肾小球细胞核数为48.6 ± 7.9个（均数±标准差），给药后1h、4 h和2d，肾小球细胞核数分别为39.8 ±6.1、37.4 ± 6.0和38.9 ± 6.8个，与对照组比较，差异有显著性（P < 0.001）。此后，肾小球核数在4天时增加至54.7 ± 11.5（P < 0.05），1周时为62.5 ± 9.6（P <0.001），2周时为64.1 ± 14.2（P < 0.001），1个月时恢复正常（P > 0.05），为49.4 ± 8.9，3个月时为50.6 ± 9.0。电镜下可见溶解期肾小球损害局限于系膜细胞，表现为水肿变性或溶解。注射后1小时，在系膜中发现兔IgG和大鼠C3;它们在第2天下降，在第4天可忽略不计。通过配对标记同位素研究，1小时时每7.6 × 104个肾小球需要11.6 μg抗体结合才能诱导系膜细胞变性。在该大鼠品系中使用的剂量下，未观察到或仅观察到蛋白尿和血清肌酐的极轻微变化。在肾小球系膜功能的定量研究中，ATS治疗大鼠的肾小球对聚集的人丙种球蛋白、聚集的牛血清白蛋白或预制的免疫复合物的摄取分别超过对照组的13.9、14.6和4.1倍，在聚集给药后4小时，但在24小时时没有。该新模型的选择性抗体诱导的肾小球细胞损伤与已建立的肾小球肾炎模型形成对比，在所述肾小球肾炎模型中，免疫存款形成和介质活化引起相对非特异性肾小球炎症。
Quantitative and qualitative studies of antibody–induced mesangial cell damage in the rat. Intravenous administration of heterologous anti-rat thymocyte serum (ATS), which reacts with a Thy-1-like antigen present on rat glomerular mesangial cells, caused lytic (1 hr to 2 days), hypercellular (4 to 14 days), and sclerotic (2 to 3 months) mesangial lesions in Lewis rats. The normal control of 48.6 ± 7.9 (mean ±SD) glomerular nuclei on histologic section decreased significantly (P < 0.001) to 39.8 ±6.1, 37.4 ± 6.0, and 38.9 ± 6.8 at one hour, four hours and two days after ATS administration, respectively. Thereafter glomerular nuclei increased to 54.7 ± 11.5 (P < 0.05) at four days, 62.5 ± 9.6 (P < 0.001) at one week and 64.1 ± 14.2 (P < 0.001) at two weeks, and normalized (P > 0.05) to 49.4 ± 8.9 at one month and 50.6 ± 9.0 at three months. By electron microscopy, glomerular damage in the lytic stage was restricted to mesangial cells and was manifested as hydropic degeneration or lysis. Rabbit IgG and rat C3 were found in the mesangium one hour after injection; they decreased at two days and were negligible at four days. By paired label isotope study, 11.6 µg of antibody bound per 7.6 × 104glomeruli at one hour was needed to induce mesangial cell degeneration. No or only minimal changes in proteinuria and in serum creatinine were observed with the dosage used in this rat strain. The glomerular uptake of aggregated human gammaglobulin, aggregated bovine serum albumin or preformed immune complexes in ATS-treated rats exceeded that in controls by 13.9, 14.6, and 4.1 times, respectively, at four hours after aggregate administration, but not at 24 hours, in quantitative studies of mesangial function. The selective, antibody–induced glomerular cell-injury of this new model contrasts with that of established models of glomerulonephritis in which immune deposit formation and mediator activation cause relatively–nonspecific glomerular inflammation.