Adjuvant-induced macrophage-dominant nephrotoxic serum nephritis in rats

Abstract

To investigate cellular mechanisms responsible for the development of crescentic glomerular lesions, we have studied the effects of complete adjuvant (CA) on subnephritogenic nephrotoxic serum (NTS) nephritis (NTS-N) in Brown Norway rats. A subnephritogenic dose of NTS, 0.02 ml per rat, was intravenously injected into rats that were previously (14 days earlier) treated intradermally with CA, incomplete adjuvant, or PBS. Proteinuria developed by day 2 only in CA-treated rats. Also, severe glomerular lesions associated with cellular crescent formation developed by day 2 only in the CA-treated rats. The glomerular extent of infiltration of IL-1beta-positive cells, MCP-1 expression level, and the number of ED1 and PCNA double-positive activated macrophages peaked on day 4 and decreased thereafter. The numbers of T lymphocytes and polymorphonuclear neutrophils did not significantly increase throughout the experiments. These results indicate that CA can potently induce crescentic NTS-N characterized by the infiltration of activated macrophages, which presumably bind to rabbit IgG on the glomerular basement membrane and may play a critical role in the development of severe NTS-N associated with crescent formation.