Effects of ziram on natural killer cell function
Human natural killer cells play a central role in immune defense with their ability to lyse tumor cells, and virally infected cells. Increase in tumor formation and viral infection may occur if NK cytotoxic function is disrupted. Ziram (zinc dithiocarbamate) is used in industry as an accelerating agent in the production of latex. In agriculture ziram is used to protect various fruits and vegetables from fungal infection. In earlier studies we have shown that continuous exposures (ranging from 1h–6days) to ziram inhibit NK lytic function. Additionally, we found that a brief (1h) exposure to ziram causes persistent loss of function. Based on these findings we hypothesized that ziram may disrupt basic metabolic and enzymatic functions in NK cells leading to alterations of NK function. We examined whether decreases in lytic function were accompanied by decreases in tumor binding function of NK cells and found ziram caused significant decreases in binding function. Further, we examined if loss of binding function was accompanied by the loss of cell surface proteins that are vital for NK cells to bind to a target cells. These studies showed that ziram caused a decrease in the presence of the cell surface protein CD16. We also examined NK cell ATP levels, since ATP is one of the driving forces in the production of cells surface proteins as well as exocytosis of cytolytic proteins onto target cells. The results showed that exposures to ziram significantly decreased ATP levels in NK cells. Finally, we studied whether ziram had an effect on MAP Kinases such as p44/42 and p38. These MAPKs have important regulatory functions in NK cells and have been shown to be activated by other environmental contaminants. The data showed, that 10 minute to 6 hour exposure of NK cells to ziram caused significant increases in the activating of phosphorylation of the MAPKs p44/42. These results suggest that ziram exposure decreases tumor binding capacity, cell surface marker expression, and NK cell ATP levels. Further, the results indicate that these changes are in common with several other environmental contaminants that have been shown to decrease NK lytic function.
Thyneice R Taylor,
"Effects of ziram on natural killer cell function"
ETD Collection for Tennessee State University.