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.
Maubach
K
K
Bath Institute for Rheumatic Diseases, University of Bath, UK.
Foey
A D
AD
Hall
N D
ND
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D010663:Phenylmercury Compounds / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D010663:Phenylmercury Compounds; C002910:4-hydroxymercuribenzenesulfonate; D010042:Ouabain; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase