The present study was undertaken in order to investigate the nature of the glomerular damage in a form of experimental immune complex nephritis. The model of autologous immune complex nephritis (AIC) 1 (Heymann's nephritis) (1) was chosen for several reasons. First, the model bears a remarkable resemblance, in terms of ultrastructural and immunofluorescence features, to an important renal disease in man, membranous glomerulonephritis. Furthermore, the model is highly reproducible. In addition, the basic pathogenetic mechanism has been thoroughly documented (2-4). Briefly, the disease is produced in rats by immunization with homologous kidney preparations, which results in the formation of autoantibodies against a renal antigen, normally found in the brush border of proximal tubules. This antigen is presumed to enter the circulation in small amounts and combine with autoantibody to form complexes which deposit in glomeruli. 2 The complexes are detected as granular deposits of immunoglobulin and complement along the epithelial side of the glomerular basement membrane. The disease, like its human counterpart, is manifested by proteinuria, which is often heavy.Our approach was to use the enzymatic tracers horseradish peroxidase (HRP) (40,000 daltons) and catalase (240,000 daltons), and the electronopaque tracer ferritin (ca. 500,000 daltons) as probe molecules with which to assess the altered functional properties of the glomerular capillary wall. These ultrastructural tracers can be directly visualized, and their location within the glomerular capillary wall can be followed at sequential intervals after intravenous injection. Such protein tracers have been extensively used to identify * This study was supported by U.S. Public Health Service grants no. AM 16392 and AM 13132.1Abbreviations used in this paper: AIC, autologous immune complex; CFA, complete Freund's adjuvant; CL, capillary lumen; DAB, 3,3' diaminobenzidine-tetra-HC1; GBM, glomerniar basement membrane; HRP, horseradish peroxidase; US, urinary space.It is of interest that a related pathogenetic mechanism may operate in man. It has recently been reported that a tubular-derived antigen may be present in the glomerular immune deposits in some cases of human membranous glomerulonephritis (5).
The capacity of intrarenal injections of bovine γ-globulin (BGG) to elicit hypersensitivity reactions was studied in guinea pigs immunized with DNP BGG or BGG immune complexes in CFA or in rats immunized with BGG in CFA. In guinea pigs it was found that heat-aggregated BGG elicited inflammatory reactions in the renal cortex, whereas soluble BGG did not. In rats only aggregated BGG was used, and this was found to be effective. The reactions were characterized by a predominantly mononuclear cell infiltrate. Transfer experiments were performed in rats and it was found that reactivity was transferrable with lymph node cells but not with serum.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.