Experimental Immune-Mediated Glomerulonephritis

Various experimental procedures were described as models for glomerulonephritis in human beings. Most of them were developed in rats and rabbits. They involve the reactions of antibodies against renal components, such as Masugi nephritis (Masugi and Sato 1934), Heymann nephritis (Heymann 1959), nephrotoxic serum nephritis (Unanue and Dixon 1967), crescentic type anti-glomerular membrane nephritis (Nagoe et al. 1994, 1998), anti-Thyl nephritis (Chen etal. 1999). 

Moreover, MRL Mpf lpr/lpr (MRL/lpr)-mice were described which spontaneously develop a severe disease with many symptoms very similar to human systemic lupus erythematodes, i.e. hypergammaglobulinemia, and glomerulonephritis (Theofilopoulos and Dixon 1981). 

Nephrotoxic serum nephritis is produced in animals by administration of heterologous antibody against 

Normal Wistar rat kidneys are fully perfused with physiologic saline through a catheter placed in the aorta. Renal cortical tissue is removed, homogenized and diluted with physiological saline at about 20% suspension. Two ml of renal cortical homogenate are emulsified with an equal volume of Freund s complete adjuvant. This emulsion is injected subcutaneously into rabbits twice a month for two months. Seven days after the last injection, the rabbits are bled from the carotid artery under anesthesia. The sera are decomple-mented for 30 min at 56 °C and absorbed with freshly harvested rat erythrocytes. 

Male Wistar-Kyoto rats weighing 150 g receive either continuous administration of the test drug by an osmotic pump (ALZA Co., Palo Alto, USA) or saline. Twenty-four hours later, the rats are injected with 1 ml of nephrotoxic serum. At 9, 12, and 14 days, urine samples are collected and urinary protein levels are measured using the Lowry method. At 14 days the rats are sacrificed under ether anesthesia, and both kidneys are removed. Portions of these tissues are processed for light microscopy, immunofluorescence staining and immunoperoxidase staining. 

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Hebert LA, Cosio FG, Birmingham DJ, Mahan JD, Sharma HM, Smead WL, Goel R. Experimental immune complex-mediated glomerulonephritis in the nonhuman primate. Kidney Int 1991 39 44-56. 

Bolton WK, Tucker FL, Sturgill BC. New avian model of experimental glomerulonephritis consistent with mediation by cellular immunity. Nonhumorally mediated glomerulonephritis in chickens. J Chn Invest 1984 73(5) 1263-1276. 

Okuda S, Languino LR, Ruoslathi E, Border WA (1990) Elevated expression of transforming growth factor-p and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. J Clin Invest 86 453 162 Rennke HG, Klein PS, Sandstrom DJ, Mendrick DL (1994) Cell-mediated immune injury in the kidney Acute nephritis induced by azobenzenearsonate. Kidney Intern 45 1044-1056... 

Over the past decade there has, as result of experimental studies, been a growing appreciation that mercury may exert an effect on the immune system. As summarized by Silbergeld and Devine [72], mercury has at least two types of effects on the immune system. First, mercury induces autoimmunity to renal basement membrane proteins, causing mercury-induced glomerulonephritis in certain strains of mice and rats. Secondly, mercury exposure impairs cell-mediated and humoral immunity by affecting Thl and Th2 responses, which in turn impairs the body s ability to effectively... 

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