Quantitative and qualitative studies of antibody-induced mesangial cell damage in the rat

摘要

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 0.05) 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 g of antibody bound per 7.6 104 glomeruli 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.