Inhibition, by lanthanides, of neutral proteinases secreted by human, rheumatoid synovium

Fragments of human, rheumatoid synovium were maintained on organ culture for three days under serumless conditions. Their conditioned media contained collagenolytic, gelatinolytic and caseinolytic activities, which were susceptible to inhibition by lanthanide ions. Of the four lanthanides tested, Sm³⁺ proved the best inhibitor of gelatinase and caseinase, while La³⁺ inhibited collagenase the most strongly. Inhibition of collagenase by La³⁺ was uncompetitive. A direct binding assay confirmed the greater association between collagen fibrils and collagenase in the presence of La³⁺. Ca²⁺ was not required for binding of the uninhibited enzyme to collagen, but acted to stabilize collagenase against thermoinactivation.