INORGANIC LEAD ACTIVATES NF-KAPPA-B IN PRIMARY HUMAN CD4(-LYMPHOCYTES() T)

Inorganic lead (Pb) is a ubiquitous environmental contaminant that pro duces a variety of effects on humoral and cell mediated immune respons es. The underlying molecular mechanisms for Pb's complex effects on th e immune system remain obscure. Many of Pb's effects on the immune sys tem could be explained through activation of the transcription factor, NF-kappa B. NF-kappa B is critical for T lymphocyte function and is a strong inducer of HIV-LTR activation. We demonstrate that Pb at physi ologically relevant concentrations activates NF-kappa B in primary hum an CD4(+) T lymphocytes. Pb-induced activation of NF-kappa B is blocke d by antibodies for p65 and p50 subunits but not cRel, indicating that the p65:p50 heterodimer (NF-kappa B) is involved. Functional activati on of gene expression by Pb was confirmed using primary CD4(+) T cells transfected with an NF-kappa B dependent reporter gene construct. Pb did not activate NF-kappa B in 4 different T cell lines, suggesting th at lymphoid cell lines may not be reliable surrogates for the study of transcriptional activation in human T cells. These data suggest that NF-kappa B may be an important molecular mediator of Pb-induced immuno toxicity. (C) 1996 Academic Press, Inc.