CRESCENTIC TYPE NEPHRITIS INDUCED BY ANTI-GLOMERULAR BASEMENT MEMBRANE (GBM) SERUM IN RATS

Abstract

An experimental model of crescentic type nephritis was established by immunizing rats that had been given at i.v. nephritogenic dose (0.4 ml/animal) of rabbit anti-rat glomerular basement membrane (GBM) serum [anti-GBM serum] with 5 mg of rabbit γ-globulin in Freund’s complete adjuvant, and the process of nephritis was investigated by means of biochemical, histopathological and immunopathological analyses. Rats treated with anti-GBM serum and then with rabbit γ-globulin (group II) showed significantly high levels or a tendency for high levels of urinary protein content, N-acetyl-β-glucosaminidase activity and plasmin-like activity from the 20th day to the 40th day observations after the induction of nephritis, when compared to rats given anti-GBM serum alone (group I). On the 40th day, plasma urea nitrogen, cholesterol and fibrinogen evels were significantly higher in group II than in group I. Glomerular histopathological examination on the 40th day revealed that the incidence and the degree of severity of crescent formation, adhesion of capillary walls to Bowman’s capsule and fibrinoid degeneration were remarkably greater in group ll than in group I. However, no significant difference was seen between both groups on the thickening of capillary walls and mesangial proliferation. Linear deposits of rabbit IgG and rat IgG along the capillary walls as well as fibrinogen-reactive material deposits in Bowman’s capsular spaces were observed by the immunofluorescence technique in both groups. The deposition of fibrinogen-reactive materials was considerably greater in group II than in group I. Moreover, the deposition of rat IgG was slightly greater in group II. These results suggest that the nephritis of group II closely resembles rapidly progessive glomerulonephritis in humans and thus seems to be an adequate experimental model for screening beneficial drugs on this type of nephritis.