Adjuvant-induced macrophage-dominant nephrotoxic serum nephritis in rats

Clin Exp Nephrol. 2005 Mar;9(1):15-23. doi: 10.1007/s10157-004-0336-5.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Autoantibodies
  • Chemokine CCL2 / metabolism
  • Ectodysplasins
  • Female
  • Fluorescent Antibody Technique
  • Freund's Adjuvant / immunology*
  • Immune Sera / immunology*
  • Immunohistochemistry / methods
  • Interleukin-1 / metabolism
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Membrane Proteins / metabolism
  • Nephritis / immunology*
  • Nephritis / metabolism
  • Nephritis / pathology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proteinuria / immunology
  • Rats
  • Rats, Inbred BN
  • Staining and Labeling
  • Time Factors

Substances

  • Antibodies
  • Autoantibodies
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Ectodysplasins
  • Immune Sera
  • Interleukin-1
  • Membrane Proteins
  • Proliferating Cell Nuclear Antigen
  • antiglomerular basement membrane antibody
  • Freund's Adjuvant