Potential withdrawal of rheumatoid synovium by the induction of apoptosis using a novel in vivo model of rheumatoid arthritis

Arthritis Rheum. 1998 Jul;41(7):1251-7. doi: 10.1002/1529-0131(199807)41:7<1251::AID-ART16>3.0.CO;2-B.

Abstract

Objective: To investigate whether Fas-mediated apoptosis has potential as a new therapeutic strategy in rheumatoid arthritis (RA) by use of a novel model of RA in which human RA tissue is grafted into SCID mice.

Methods: Fresh rheumatoid synovial tissue including joint cartilage was grafted subcutaneously into the backs of SCID mice. Six weeks after engraftment, anti-Fas monoclonal antibody was injected intraperitoneally. Time-related apoptotic changes caused by anti-Fas monoclonal antibody in grafted synovium were evaluated by nick end-labeling histochemistry.

Results: Thirty-six hours after the injection, diffuse apoptotic changes were observed in the grafted synovia. Four weeks after the injection, rheumatoid synovial tissue diminished.

Conclusion: This is the first report concerning the present effectiveness of anti-Fas monoclonal antibody in diminishing rheumatoid synovium in vivo, and suggests the possibility of a new strategy for treating rheumatoid arthritis by inducing Fas-mediated apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Disease Models, Animal
  • Histocytochemistry
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Mice
  • Mice, SCID
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology*
  • Synovial Membrane / transplantation
  • Time Factors
  • fas Receptor / immunology*

Substances

  • Antibodies, Monoclonal
  • fas Receptor