To investigate the production of membrane-expressed urokinase-type plasminogen activator receptor (muPAR) and cytoplasmic-expressed uPAR (cuPAR) in synovial tissue from patients with rheumatoid arthritis (RA) and analyze their relationship with the severity of synovial inflammation in RA.
MuPAR and cuPAR were measured with indirect immunofluorescence (IIF) and immunoperoxidase histochemical analysis of the synovial tissue sections from 18 patients with RA, 10 patients with osteoarthritis (OA) and 4 healthy subjects. The association of uPAR expression with the severity of synovitis in RA was then analyzed.
MuPAR positive cells were detected in approximately (66.0+/-9.4)% of the RA synovial cells, distributed predominantly in vascular endothelial cells and fibroblast cells. While cuPAR positive cells were found in about (61.0+/-5.8)% of the RA synovial cells, including subsynovial and interstitial macrophage-like cells, mononuclear leukocytes and fibroblast cells. Both the muPAR and cuPAR expression were much more increased in RA synovial tissue than those in OA synovial tissue. Furthermore, the number of muPAR (r=0.672, P<0.01) and cuPAR (r=0.649, P<0.01) positive cells in synovial tissue was also found to be correlated significantly with the severity of synovial inflammation in RA patients.
The up-regulated expression of muPAR in synovial vascular endothelial cells suggests an important role of this molecule in angiogenesis in RA and the increased production of cuPAR in synovial inflammatory cells indicates the involvement of cuPAR in the inflammatory process in RA.