Effect of a series of triorganotins on the immune function of human natural killer cells

Natural killer (NK) cells are our initial immune defense against viral infections and cancer development. They are able to destroy tumor and virally infected cells. Thus, agents that are able to interfere with their function increase the risk of cancer and/or infection. Organotins (OTs) have been shown to interfere with the tumor-destroying function of human NK cells. The purpose of the current study was to explore the relationship of a series of triorganotins, that differ in structure by only a single organic group, for their capacity to block NK tumor-cell destroying (lytic) function. Here we examine the series: trimethyltin (TMT), dimethylphenyltin (DMPT), methyldiphenyltin (MDPT), and triphenyltin (TPT). NK cells were exposed to TMT, DMPT, MDPT or TPT for 1, 24, 48 h, or 6 d. A 1 h exposure to TMT, at concentrations as high as 20 μM, had no effect on lytic function. However, concentrations as low as 2.5 μM were able to decrease NK tumor-destroying function after 6 d. A 1 h exposure to DMPT had no effect on lytic function, however, after 6 d there was an 80–90% decrease in lytic function at 1 μM. Exposure to MDPT (as low as 2.5 μM) decreased NK function at 1 h, after 6 d there was as much as a 90% decrease at concentrations as low as 100 nM MDPT. TPT decreased lytic function in a manner similar to MDPT, however, it was more effective at 1 h than MDPT. The effect of the triorganotins on the ability of NK cells to bind to targets was studied, to determine if this contributed to the loss of lytic function. The relative immunotoxic potential of this series of compounds is TPT ≈ MDPT > DMPT > TMT.