Impaired activity of thiol-dependent ATPases in rheumatoid mononuclear cell membranes

Ion-motive ATPase play an essential role in many aspects of cell biology, including mononuclear cell (MNC) functions relevant to chronic inflammation. For example, ouabain, a specific inhibitor of Na+, K+ ATPase, suppresses both T and B cell proliferation but induces synthesis of IL-1. Using a cytochemical assay quantified by microdensitometry, total and ouabain-sensitive ATPase activities have been compared in MNC from rheumatoid and control subjects. The sensitivity of these enzymes to inactivation by thiol-blocking reagents has been studied by preincubation with an impermeant SH blocker p-hydroxymercuriphenylsulphonate (pHMPSA). The results show that rheumatoid MNC have significantly impaired ATPase activity compared to healthy cells and that both total and ouabain-sensitive ATPase activities are readily inhibited by pHMPSA. The depressed ATPase activity in rheumatoid MNC could thus be due to blockade/oxidation of a reactive surface thiol, and could contribute to perpetuation of the chronic inflammatory process in these patients.