Characterization of Intracellular Calcium Responses Produced by Polycyclic Aromatic Hydrocarbons in Surface Marker-Defined Human Peripheral Blood Mononuclear Cells

Abstract

Previous studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP) and 7,12-dimethybenz[a]anthracene (DMBA), and possibly 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), may exert their immunosuppressive effects by altering intracellular Ca2+homeostasis in lymphocytes. In these studies, we examined the effects of two immunosuppressive PAHs (BaP and DMBA), two nonimmunosuppressive PAHs (benzo[e]pyrene (BeP) and anthracene (ANTH)), and TCDD on intracellular Ca2+levels in surface marker-defined human peripheral blood mononuclear cells (HPBMC). BaP and DMBA, but not BeP and ANTH, were found to produce a time-dependent increase in intracellular Ca2+with maximal effects achieved following 42- to 66-hr exposures. In a series of studies with HPBMC obtained from 10 donors exposedin vitrofor 42 hr, BaP and DMBA were found to produce a significant increase in Ca2+in CD3+T cells, CD19+B cells, and CD14+monocytes. BeP and ANTH did not produce a statistically significant increase in Ca2+in the group of donors, but occasionally produced an apparent nonspecific elevation of Ca2+in HPBMC from individual donors. Interestingly, TCDD produced a small and statistically significant increase in Ca2+only in B cells analyzed for the pooled 10 donors. Certain BaP metabolites, such as the 7,8-dihydrodiol and the 7,8-diol-9,10-epoxide, were more effective in elevating Ca2+in HPBMC lymphocytes at 20 hr than was BaP. These results demonstrate in normal HPBMC that immunosuppressive PAHs alter intracellular Ca2+homeostasis in B cells, T cells, and monocytes, and suggest that P450 metabolism may play an important role in the immunotoxicity of certain PAHs.