Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice.
Rheumatoid arthritis (RA) has been thought to be largely a T-cell-mediated disease. To evaluate the role of T-cell-independent pathways in RA, we examined the interaction between isolated RA synovial fibroblasts and normal human cartilage engrafted into SCID mice in the absence of T cells and other human cells. The expression of cartilage-de grading enzymes and adhesion molecules was examined by immunohistochemistry and in situ hybridization techniques. The RA synovial fibroblasts invaded the cartilage and kept their transformed appearing cellular shape. They expressed VCAM-1 and produced the cathepsins L and B at the site of invasion. We conclude that RA synovial fibroblasts maintain their invasive and destructive behavior over longer periods of time in the absence of human T cells, indicating that T-cell-independent pathways play a significant role in rheumatoid joint destruction.
Division of Clinical Immunology, University of Alabama at Birmingham, USA.
U
U
Müller-Ladner
J
J
Kriegsmann
B N
BN
Franklin
S
S
Matsumoto
T
T
Geiler
R E
RE
Gay
S
S
Gay
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology* / Q000637:transplantation*; D002403:Cathepsins / Q000096:biosynthesis; D002448:Cell Adhesion; D002455:Cell Division; D005347:Fibroblasts / Q000473:pathology* / Q000637:transplantation*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010003:Osteoarthritis / Q000473:pathology; D013583:Synovial Membrane / Q000637:transplantation*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D019010:Vascular Cell Adhesion Molecule-1; D002403:Cathepsins