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.

Abstract

To evaluate the occurrence of gelatinase-B (matrix metalloproteinase 9, MMP-9) in synovial fluids (SF) of patients with arthritis to investigate the possible role of this neutral MMP in joint destruction. In paired (series I) and unpaired SF (series II) we examined the occurrence of gelatinase-B, prostromelysin-1, and urokinase-type plasminogen activator (u-PA). In the paired SF a parallelism between the presence of activated gelatinase-B and the local arthritis activity scores of the knees was observed. Activated gelatinase-B correlated well with the presence of stromelysin-1 and u-PA, 2 enzymes probably involved in the activation process of gelatinase-B. In the 2nd series, activated gelatinase-B was found in 56 SF samples, whereas 82 samples did not exhibit activated gelatinase-B. The SF samples with the activated form of gelatinase-B showed a significantly higher ability to induce permeability changes in cultured monolayers of human endothelial cells, had more myeloperoxidase activity--secreted by infiltrated leukocytes--and had higher u-PA antigen concentrations, compared to SF samples without the activated form of gelatinase-B. Our data suggest that the presence of gelatinase-B is a reflection of the inflammatory condition of the joints of patients with arthritis, and that the activation of gelatinase-B in the joints, which may occur in a u-PA/plasmin dependent and/or a stromelysin dependent way, contributes to the progression of arthritis.