Increased microbicidal activity of human monoblastoid cells upon long-term exposure to dideoxycytidine

详细信息    查看全文

• 作者：Brandi ; Giorgio ; Antonelli ; Antonella ; Amagliani ; Giulia ; Albano ; Amedeo ; Magnani ; Mauro
• 关键词：nucleoside analogues ; U937 cells ; phagocytosis ; oxidative burst ; 2&prime ; 3&prime ; -dideoxycytidine
• 刊名：Life Sciences
• 出版年：1997
• 出版时间：January 17, 1997
• 年：1997
• 卷：60
• 期：8
• 页码：519-528
• 全文大小：995 K

文摘

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-resistant cells (U937-R). In the present work we investigated some important biochemical properties and functional activities of these resistant cells. The results obtained show that U937-R maintained the properties of cell aggregation, adhesion and differentiation. Basal respiration, protein kinase C activity, superoxide anion release and intracellular free calcium were all increased in the drug-resistant line. Phagocytosis 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). Similarly, 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 presented in this paper provide evidence of an increased microbicidal activity of human monocytic cells upon long term exposure to ddC, most likely due to an increased oxidative metabolism.