INCREASED MICROBICIDAL ACTIVITY OF HUMAN MONOBLASTOID CELLS UPON LONG-TERM EXPOSURE TO DIDEOXYCYTIDINE

2',3'-Dideoxycytidine (ddC) is a nucleoside analogue currently used in AIDS therapy. We had previously found that long term exposure of U937 human monoblastoid cells to ddC induces the selection of drug-resista nt cells (U937-R). In the present work we investigated some important biochemical properties and functional activities of these resistant ce lls. The results obtained show that U937-R maintained the properties o f cell aggregation, adhesion and differentiation. Basal respiration, p rotein kinase C activity, superoxide anion release and intracellular f ree calcium were all increased in the drug-resistant line. Phagocytosi s of fungi (Candida albicans) and bacteria (Staphylococcus aureus and Salmonella anatum) were similar in U937 and U937-R cells. Killing of C . albicans was significantly higher in drug-resistant cells (29.07 +/- 2.23 % of killing vs 19.07 +/- 2.01 in the control; p<0.001). Similar ly, the bacterial killing was enhanced in U937-R cells (34.07 +/- 8.06 % vs 22.60 +/- 4.41 % in the control; p < 0.05). Thus, the results pr esented in this paper provide evidence of an increased microbicidal ac tivity of human monocytic cells upon long term exposure to ddC, most l ikely due to an increased oxidative metabolism.