Effects of ziram on tumor-cell-binding capacity, cell-surface marker expression, and ATP levels of human natural killer cells

Human natural killer (NK) cells are central in immune defense against tumor and virally infected cells. Ziram is used as an accelerating agent in latex production and as an agricultural fungicide. Previous studies showed that continuous exposure to ziram inhibits NK lytic function. Additionally, they showed that a brief (1 h) exposure to ziram caused persistent loss of lytic function. This study examined whether decreases in lytic function were accompanied by decreases in the target-binding function of NK cells and found that some, but not all, exposures to ziram caused significant decreases in binding function. Ziram exposures that caused a loss of binding function were examined for effects on expression of key NK cell-surface proteins needed for binding to targets. Exposure to 2 μM ziram for 1 h followed by 24 or 48 h in ziram-free media decreased CD16 expression, but no other exposures caused decreases in cell-surface proteins. As decreases in adenosine triphosphate (ATP) could be in part responsible for loss of lytic function, the effect of ziram exposures on ATP levels of NK cells were examined. Certain ziram exposures decreased ATP levels in NK cells, but a decrease in ATP was not necessarily associated with a decrease in lytic function. The results indicate that ziram-induced losses of lytic function cannot be fully explained by alteration in binding, cell-surface protein expression, or ATP levels