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.
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 SCIDmice. METHODS: Fresh rheumatoid synovial tissue including joint cartilage was grafted subcutaneously into the backs of SCIDmice. 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.
Authors: Kai Zhang; Tang-Hong Jia; David McQueen; Wei-Ming Gong; David C Markel; Paul H Wooley; Shang-You Yang Journal: Inflamm Res Date: 2009-05-30 Impact factor: 4.575