Inhibitor regulation of tissue kallikrein activity in the synovial fluid of patients with rheumatoid arthritis.

Tissue kallikrein (TK) and alpha 1-antitrypsin (AT)/TK complexes can be detected in SF from patients with RA if components of the fluids which interfere with the detection of TK are removed. alpha 2-Macroglobulin (alpha 2-M) in SF was demonstrated to contain trapped proteases which were still active in amidase assays. Removal of alpha 2-M from RA SF reduced their amidase activity. However, at least some of the remaining activity was due to TK because it was soya bean trypsin inhibitor resistant and trasylol sensitive and was partly removed by affinity chromatography on anti-TK sepharose. Removal of RF from the fluids reduced the values obtained for TK levels by ELISA. Addition of SF to human urinary kallikrein (HUK) considerably reduced the levels of TK detected suggesting the presence of a TK ELISA inhibitor in the fluids. Removal of components of > 300 kDa from SF markedly reduced the TK ELISA inhibitory activity and increased the values for both the TK and alpha 1-AT/TK levels in fluids as measured by ELISA. It is considered this novel inhibitor does not bind to the active site of TK but rather binds to the site reactive with anti-TK antibodies.