ACTIVATED GELATINASE-B (MMP-9) AND UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN SYNOVIAL-FLUIDS OF PATIENTS WITH ARTHRITIS - CORRELATION WITH CLINICAL AND EXPERIMENTAL-VARIABLES OF INFLAMMATION

Objective. To evaluate the occurrence of gelatinase-B (matrix metallop roteinase 9, MMP-9) in synovial fluids (SF) of patients with arthritis to investigate the possible role of this neutral MMP in joint destruc tion. Methods. In paired (series I) and unpaired SF (series II) we exa mined the occurrence of gelatinase-B, prostromelysin-1, and urokinase- type plasminogen activator (u-PA). Results. In the paired SF a paralle lism between the presence of activated gelatinase-B and the local arth ritis activity scores of the knees was observed. Activated gelatinase- B correlated well with the presence of stromelysin-1 and u-PA, 2 enzym es probably involved in the activation process of gelatinase-B. In the 2nd series, activated gelatinase-B was found in 56 SF samples, wherea s 82 samples did not exhibit activated gelatinase-B. The SF samples wi th the activated form of gelatinase-B showed a significantly higher ab ility to induce permeability changes in cultured monolayers of human e ndothelial cells, had more myeloperoxidase activity - secreted by infi ltrated leukocytes - and had higher u-PA antigen concentrations, compa red to SF samples without the activated form of gelatinase-B. Conclusi on, Our data suggest that the presence of gelatinase-B is a reflection of the inflammatory condition of the joints of patients with arthriti s, and that the activation of gelatinase-B in the joints, which may oc cur in a u-PA/plasmin dependent and/or a stromelysin dependent way, co ntributes to the progression of arthritis.