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

Abstract

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 less than 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 less than 0.05) at four days, 62.5 +/- 9.6 (P less than 0.001) at one week and 64.1 +/- 14.2 (P less than 0.001) at two weeks, and normalized (P greater than 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 micrograms of antibody bound per 7.6 X 10(4) 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.(ABSTRACT TRUNCATED AT 250 WORDS)