Differential effects of mercury, lead, and cadmium on IL-2 production by Jurkat T cells.
Mercury, lead, and cadmium are widespread and highly toxic pollutants. The aim of this study was to determine the effects of sublethal doses of CH(3)HgCl, CdCl(2), and PbCl(2) on IL-2 production by T lymphocytes. Jurkat T cells were stimulated by triggering CD3 and CD28 molecules before, in conjunction with, or following heavy metal exposure. Heavy metals, individually or mixed together at equimolar concentrations, were used. Results demonstrated that low, noncytotoxic doses of metals induce tyrosine phosphorylation. Mercury and lead (1 microM) inhibit IL-2 production regardless of the state of T cell activation. Cadmium stimulated IL-2 production only in preactivated T cells. Surprisingly, a mixture of these three metals had no effect. We subsequently determined the effects of heavy metals on NFAT (nuclear factors of activated T cells) activity. When cells were stimulated by potent stimulation involving the CD3 and CD28 molecules, an increased NFAT activation was noted when the cells were exposed to mercury and to the metal mixture. Activation with PMA/calcium ionophores indicated that the target of heavy metals is located downstream from PKC and calcium mobilization. These results suggest that the state and mode of T cell activation are important parameters to consider in heavy metal toxicity.
Colombo
Myrian
M
Centre de recherche en santé humaine, INRS-Institut Armand Frappier, Université du Québec, Pointe-Claire, QC, Canada.
Hamelin
Claudine
C
Kouassi
Edouard
E
Fournier
Michel
M
Bernier
Jacques
J
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D019256:Cadmium Chloride / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D007854:Lead / Q000633:toxicity*; D008213:Lymphocyte Activation; D008767:Methylmercury Compounds / Q000633:toxicity*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D013601:T-Lymphocytes / Q000187:drug effects*; D014157:Transcription Factors / Q000187:drug effects
D018106:CD28 Antigens; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008767:Methylmercury Compounds; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D007854:Lead; C029891:lead chloride; D019256:Cadmium Chloride; C004925:methylmercuric chloride