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Arch Toxicol (2013) 87:249258 DOI 10.1007/s00204-012-0926-z
INORGANIC COMPOUNDS
Impact of lead and mercuric ions on the interleukin-2-dependent proliferation and survival of T cells
Andrea Jorissen Laura M. Plum
Lothar Rink Hajo Haase
Received: 6 March 2012 / Accepted: 6 August 2012 / Published online: 22 August 2012 Springer-Verlag 2012
Abstract Mercury and lead are widespread in the environment, causing chronic exposure of a large population to low concentrations of these metals. While several studies demonstrated that low levels of both metals affect the immune system, little is known about underlying molecular mechanisms. The objective of this study was to investigate the impact of mercuric (Hg2?) and lead (Pb2?) ions on T cells. Up to 100 lM Pb(NO3)2 had no effect on cellular viability and proliferation. In contrast, HgCl2 caused a concentration-dependent decline of viable leukocytes and especially of activated T cells. Additionally, Hg2? induced reactive oxygen species (ROS) generation accompanied by the loss of mitochondrial transmembrane potential, measured by Dihydrorhodamine and Rhodamine-123, respectively. The antioxidant N-acetylcysteine partially reversed the toxic effects of Hg2?, pointing to an involvement of ROS. The major cytokine controlling T-cell survival and proliferation is interleukin (IL)-2. Hg2? had no effect on the secretion of IL-2, but on IL-2 mediated signal transduction pathways, reducing phosphorylation of the downstream kinases ERK1/2 and AKT. Moreover, Hg2? led to an arrest of the cells in the S phase of the cell cycle. Taken together, these data t a model in which Hg2? disrupts mitochondria, and the resulting release of ROS inhibits IL-2-dependent signal transduction, reducing proliferation and survival of T cells.
Keywords Mercury Lead T cells IL-2
Proliferation ROS
Introduction
Mercury and lead are two widespread pollutants in the environment. Thus, a large population is permanently exposed to low levels of these metals. Beside the consistent release from the earths crust (Daz Rizo et al. 2011; Vas and Monestier 2008), anthropogenic causes such as industrial waste dumping and the utilization of fossil fuels increase the contamination of air, soil, and water, augmenting exposure of humans and animals. Like many metals, mercury and lead bioaccumulate in the food chain. The ingestion of contaminated food presents one main route of exposure of humans to these metals (Bernier et al. 1995; Vas and Monestier 2008). For mercury, the...