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

Tissue kallikrein (TK) and 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.
2-Macroglobulin (2-M) in SF was demonstrated to contain trapped
proteases which were still active in amidase assays. Removal of 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
l-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.