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. 2015 May;30(5):559-71.
doi: 10.1002/tox.21932. Epub 2013 Dec 20.

Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin

Shanieek Lawrence  1 , Jacqueline Reid, Margaret Whalen
Affiliations

Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin

Shanieek Lawrence et al. Environ Toxicol. 2015 May.

Abstract

Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 - 2.5 nM) and DBT (5 - 0.05 µM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure.

Keywords: NK cells; PBMCs; dibutyltin; interferon gamma; tributyltin.

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Figures

Figure 1
Figure 1
Effects of 24 h, 48 h and 6 day exposures to TBT and DBT on IFNγ secretion from highly purified human NK cells, monocyte-depleted PBMCs, and PBMCs in an individual donor. A) NK cells exposed to 0–200 nM TBT (donor KB147). B) Monocyte-depleted PBMCs exposed to 0–200 nM TBT (donor F142). C) PBMCs exposed to 0–200 nM TBT (donor F120). D) NK cells exposed to 0–5 μM DBT (donor KB155). E) Monocyte-depleted PBMCs exposed to 0–5 μM DBT (donor F142). F) PBMCs exposed to 0–5 μM DBT (donor F120). The data point for a 48 h exposure of NK cells to 2.5 nM TBT (177±120 pg/mL) was omitted in (A) as it was not significant and made it difficult to see the effects at other concentrations.
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