No abstract

This study investigated whether exposures to butyltins (BTs), tributylin (TBT) and dibutyltin (DBT) were able to alter cytosolic calcium levels in human natural killer (NK) cells. Additionally, the effects of cytosolic calcium ion increases on the activation state of mitogen activated protein kinases (MAPKs) in NK cells were also investigated. NK cells are an intital immune defense against the development of tumors or viral infections. TBT and DBT are widespread environmental contaminants, due to their various industrial applications. Both TBT and DBT have been shown to decrease the ability of NK cells to lyse tumor cells (lytic function). TBT has also been shown to activate MAPKs in NK cells. The results of this study indicated that TBT increased cytosolic calcium levels by as much as 100% after a 60 min exposure to 500 nM TBT while DBT increased cytosolic calcium levels to a much smaller extent (and required higher concentrations). The results also indicated that increases in cytosolic calcium could activate MAPKs but only for a short period of time (5 min), while previous studies showed that activation of MAPKs by TBT last for at least 6 hours. Thus, it appears that TBT stimulated increases in cytosolic calcium may contribute to, but are not fully responsible for, TBT-induced activation of MAPKs.

Tributyltin (TBT) is a toxic man‐made compound that was used in wood preservation, marine antifouling paints, disinfection of circulating industrial cooling waters and slime control in paper mills. Detectable levels have been found in human blood. Exposure to TBT decreases the tumor‐cell lysing (lytic) function of human natural killer (NK) lymphocytes. In this study we assessed the effects of concentrations of TBT that have been shown to decrease NK lytic function on the phosphorylation states of protein tyrosine kinases (PTKs) (Syk, Zap‐70, Src and Pyk) and phospholipase C gamma (PLCγ) in NK cells. Exposure to 500 nM TBT caused no change in phosphorylation of any of the protein tyrosine kinases. A 60 min exposure of NK cells to 500 nM TBT did not significantly affect the phosphorylation state of PLCγ1 at any of the lengths of exposure. However, total levels of PLCγ were increased by almost 50% after 60 minutes of exposure to 500 nM TBT. Exposure of NK cells to 300 nM TBT for 5–60 min caused no significant changes in the phosphorylation state or total level of any of the PTKs or PLCγ. Exposure of NK cells to 200 nM TBT for 24 h caused no significant changes in the PTK or PLCγ phosphorylation state or total levels. Cells that were exposed to 300 nM TBT for 1h followed by 24h or 48h in TBT‐free media showed a significant increase in the phosphorylated forms of Syk (Tyr525) and Zap‐70 after 24 h in TBT‐free media but not after 48 h. These data indicate that in vitro exposure to TBT, under some conditions, induced changes in PLCγ, Phospho‐syk(Tyr525) and Phospho‐zap70. Supported by NIH grant 2S06GM0809228.