PLASMINOGEN ACTIVATION IN SYNOVIAL TISSUES - DIFFERENCES BETWEEN NORMAL, OSTEOARTHRITIS, AND RHEUMATOID-ARTHRITIS JOINTS

Objective-To analyse the functional activity of the plasminogen activa tors urokinase (uPA) and tissue type plasminogen activator (tPA) in hu man synovial membrane, and to compare the pattern of expression betwee n normal, osteoarthritic, and rheumatoid synovium. The molecular mecha nisms underlying differences in PA activities between normal and patho logical synovial tissues have been further examined. Methods-Synovial membranes from seven normal (N) subjects, 14 osteoarthritis (OA), and 10 rheumatoid arthritis (RA) patients were analysed for plasminogen ac tivator activity by conventional zymography and in situ zymography on tissue sections. The tissue distribution of uPA, tPA, uPA receptor (uP AR), and plasminogen activator inhibitor type-1 (PAI-1) was studied by immunohistochemistry. uPA, tPA, uPAR, and PAI-1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively. Results-All normal and most OA synovial tissues express ed predominantly tPA catalysed proteolytic activity mainly associated to the synovial vasculature. In some OA, tPA activity was expressed to gether with variable amounts of uPA mediated activity. By contrast, mo st RA synovial tissues exhibited considerably increased uPA activity o ver the proliferative lining areas, while tPA activity was reduced whe n compared with N and OA synovial tissues. This increase in uPA activi ty was associated with increased levels of uPA antigen and its corresp onding mRNA, which were localised over the synovial proliferative lini ng areas. In addition, in RA tissues, expression of the specific uPA r eceptor-(uPAR) and of the plasminogen activator inhibitor-type 1 (PAI- 1) were also increased. Conclusion-Taken together, these results show an alteration of the PA/plasmin system in RA synovial tissues, resulti ng in increased uPA catalytic activity that may play a part in tissue destruction in RA.