IMPAIRED ACTIVITY OF THIOL-DEPENDENT ATPASES IN RHEUMATOID MONONUCLEAR CELL-MEMBRANES

Ion-motive ATPases play an essential role in many aspects of cell biol ogy, including mononuclear cell (MNC) functions relevant to chronic in flammation. For example, ouabain, a specific inhibitor of Na+, K+ ATPa se, suppresses both T and B cell proliferation but induces synthesis o f IL-1. Using a cytochemical assay quantified by microdensitometry, to tal 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 preinc ubation with an impermeant SH blocker p-hydroxy-mercuriphenylsulphonat e (pHMPSA). The results show that rheumatoid MNC have significantly im paired ATPase activity compared to healthy cells and that both total a nd 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.