Potentiation by thiopurines and sulfhydryl-reactive agents of the inhibition by 3-deazaadenosine of mononuclear phagocytes.
Combination effects of 3-deazaadenosine (c3Ado) on antibody-dependent phagocytosis in mouse resident peritoneal cells and human peripheral blood monocytes precultured with cytotoxic thiols, azathioprine (AZA) or 6-mercaptopurine (6-MP), and thiol-reactive agents, 2-cyclohexene-1-one (2-CH) or ethacrynic acid (ETA), are described. In the mouse cell preparations, a non-inhibitory concentration of 10 microM AZA or 6-MP potentiated the inhibition by 5 and 10 microM c3Ado of phagocytosis. Higher concentrations of AZA or 6-MP (50, 100 microM) and c3Ado (40, 50 microM) were needed to achieve similar effects in human monocytes. Both 2-CH (50 microM) and ETA (25 microM) inhibited mouse cell phagocytosis and acted synergistically with c3Ado. Precultivation of mouse cells with an inhibitor of glutathione synthesis, buthionine sulfoximine (BSO, 50 microM) caused no inhibition of phagocytosis and no potentiation of the inhibition by c3Ado, although BSO potentiated the inhibition by 2-CH (50 microM). In human monocytes, non-inhibitory concentrations (10 and 25 microM) of gold sodium thiomalate (GST), AZA, and c3Ado, but not 6-MP, potentiated the inhibition by 2-CH (25-37.5 microM) of phagocytosis. Results are discussed in connection with the possible modulation by endogenous sulfhydryl-reactive metabolites of phospholipid turnover of the effects of c3Ado.
Medzihradsky
J L
JL
Division of Experimental Therapy, Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Wilson
J G
JG
D000818:Animals; D001379:Azathioprine / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D003512:Cyclohexanones / Q000494:pharmacology*; D004357:Drug Synergism; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D015122:Mercaptopurine / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D010586:Phagocytes / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D014372:Tubercidin / Q000494:pharmacology*
D003512:Cyclohexanones; C018258:3-deazaadenosine; D008717:Methionine Sulfoximine; C028215:2-cyclohexen-1-one; D019328:Buthionine Sulfoximine; D015122:Mercaptopurine; D005978:Glutathione; D014372:Tubercidin; D004976:Ethacrynic Acid; D001379:Azathioprine