Immunotoxicity of environmentally relevant concentrations of butyltins on human natural killer cells in vitro

The widespread environmental contamination, bio-accumulation, and toxic eff ects of butyltins (BTs) in wildlife is well documented, but the role of BTs in debilitating human immune function mediated through natural killer (NK) lymphocytes (a primary immune defense against tumor and virally infected c ells) has not been described. In this study, we assessed the effects of in vitro exposure to a range of concentrations (encompassing environmentally r elevant concentrations) of MET, DBT, and TBT on human natural killer lympho cytes obtained from adult male and female donors. TBT inhibited the tumor-k illing capacity of NK cells when the NK cells were pretreated in vitro at 2 00 nM for as little as 1 h. Inhibition of NK cytotoxic function ranged from 40 to greater than 90%. The toxic potential of butyltins followed the orde r of TBT > DBT > MET. Conjugation assays revealed that after a 24-h exposur e to TBT, there was about a 50% decrease in NK cell binding to tumor cells, indicating alteration of the NK cell receptors for tumor cells. Analysis o f whole-blood samples for BTs revealed the presence of detectable concentra tions of MET, DBT, and TBT in all of the donors, indicating possible exposu re of NK cells to BTs in the blood. The results of this study provide evide nce that butyltin compounds significantly inhibit NK cell function and poss ible NK cell-mediated immunotoxic potential in humans. (C) 1999 Academic Pr ess.