Effects of Tributyltin on Protein Tyrosine Kinases and Phospholipase C Gamma in Human Natural Killer Cells

ABSTRACT

Tributyltin (TBT) has been 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 protein tyrosine kinases (PTKs) (Syk, Zap-70, Src, and Pyk) and phospholipase C gamma (PLC-γ) in NK cells. Exposure to 500 nM TBT caused no change in phosphorylation of any of the PTKs. A 60-min exposure of NK cells to 500 nM TBT did not significantly affect the phosphorylation state of PLC-γ at any of the lengths of exposure. However, total levels of PLC-γ were increased by almost 50% after this exposure. Exposure of NK cells to 300 nM TBT for 5 to 60 min caused no significant changes in the phosphorylation state PTKs or PLC-γ. Exposure of NK cells to 200 nM TBT for 24 h caused no significant changes in the PTK phosphorylation state or total levels. Cells that were exposed to 300 nM TBT for 1 h followed by 24 h or 48 h in TBT-free media showed a significant increase in the phosphorylated forms of Syk and Zap-70 after 24 h in TBT-free media but not after 48 h. These data indicate that in vitro exposure to TBT caused no changes in PTK or PLC-γ phosphorylation under most conditions.

KEYWORDS :

• Tributyltin
• NK Cells
• Tyrosine Kinases
• Phospholipase C