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


CONCLUSIONS
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.
Sakai
K
K
Toyama Medical and Pharmaceutical University, Toyama City, Japan.
Matsuno
H
H
Morita
I
I
Nezuka
T
T
Tsuji
H
H
Shirai
T
T
Yonehara
S
S
Hasunuma
T
T
Nishioka
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016513:Mice, SCID; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D013997:Time Factors; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019014:fas Receptor