PLASMINOGEN ACTIVATORS AND THEIR INHIBITORS IN SYNOVIAL-FLUIDS FROM NORMAL, OSTEOARTHRITIS, AND RHEUMATOID-ARTHRITIS KNEES

Objectives-To establish baseline concentrations of plasminogen activat ors and their inhibitors in normal knee synovial fluids, and to compar e them with well characterised osteoarthritis (OA) and rheumatoid arth ritis (RA) knee fluids. Methods-A total of 26 normal subjects, 71 pati ents with OA, and 17 patients with RA underwent knee aspiration. Patie nts with OA were subclassified according to presence of nodal generali sed OA (NGOA) and synovial fluid calcium pyrophosphate crystals. Clini cal assessment of inflammation (graded 0-6) was undertaken in OA and R A patients. Plasminogen activator (PA), plasminogen activator inhibito r (PAI), and urokinase-type PA receptor (uPAR) antigen concentrations were determined by enzyme linked immunosorbent assay. The species of P As present were determined by sodium dodecyl sulphate-polyacrylamide g el electrophoresis. Results-Concentrations of all antigens (uPA, tissu e-type PA (tPA), uPAR, and PAI-1), were significantly greater in RA th an OA; those in OA were significantly greater than normal. The concent rations showed no direct association with clinically assessed inflamma tion of the knee. In normal fluids, no associations with age were obse rved. Antigen concentrations (uPA, tPA, and uPAR) in NGOA differed fro m those in other subclasses of OA, but the species of PA present did n ot appear to vary between disease groups. The predominant PA appeared to have identity with uPA. Conclusion-Because of the greater concentra tions of these antigens in OA compared with normal fluids, OA cannot b e used as a surrogate normal control in studies of the PA/PAI system. Alteration of the PA/PAI system was confirmed in RA and OA knee fluids , with greater changes evident in RA. The finding of different concent rations of PA antigens in NGOA compared with other OA fluids further s upports a different pathogenic mechanism in this subset.