Inorganic Compounds

Archives of Toxicology

, Volume 87, Issue 2, pp 249-258

Impact of lead and mercuric ions on the interleukin-2-dependent proliferation and survival of T cells

  • Andrea JorissenAffiliated withInstitute of Immunology, Medical Faculty, RWTH Aachen University
  • , Laura M. PlumAffiliated withInstitute of Immunology, Medical Faculty, RWTH Aachen University
  • , Lothar RinkAffiliated withInstitute of Immunology, Medical Faculty, RWTH Aachen University
  • , Hajo HaaseAffiliated withInstitute of Immunology, Medical Faculty, RWTH Aachen University Email author 

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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 μM 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 fit 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