Induction of systemic lupus erythematosus syndrome in BALB/c mice by immunization with active chromatin

Acta Pharmacol Sin. 2004 Jun;25(6):807-11.

Abstract

Aim: To establish an animal model for systemic lupus erythematosus (SLE)-like syndrome in mice.

Methods: BALB/c mice were immunized with active chromatin isolated from ConA-activated syngeneic spleno-lymphocytes. Plasma samples of mice were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of IgG anti-dsDNA, -ssDNA, and anti-histone antibodies. Tumor necrosis factor-alpha (TNF-alpha) in serum was measured by ELISA. Spleno-lymphocyte proliferation assays and the levels of interferon-gamma (IFN-gamma) in supernatants were tested respectively. Proteinuria was measured. Kidneys were examined by direct immunohistochemical method and light microscopy.

Results: Anti-ds DNA, ssDNA, and histone antibodies were induced in active chromatin-immunized mice, the proliferation response of splenocytes to ConA and LPS were reduced, levels of interferon-gamma in supernatants and TNF-alpha in serum were lowered. Lupus nephritis was assessed by the presence of Ig deposits, glomerular pathology and proteinuria.

Conclusion: The active chromatin-induced SLE-like mouse model was similar to idiopathic SLE in human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / analysis
  • Cell Division
  • Chromatin
  • DNA / immunology
  • DNA, Single-Stranded / immunology
  • Disease Models, Animal*
  • Female
  • Histones / immunology
  • Immunoglobulin G / analysis
  • Interferon-gamma / blood
  • Kidney / pathology
  • Lupus Erythematosus, Systemic / chemically induced*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Nephritis / chemically induced
  • Lupus Nephritis / pathology
  • Lymphocytes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Autoantibodies
  • Chromatin
  • DNA, Single-Stranded
  • Histones
  • Immunoglobulin G
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • DNA