Characterization of intracellular calcium responses produced by polycyclic aromatic hydrocarbons in surface marker-defined human peripheral blood mononuclear cells.
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 exposed in vitro for 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.
Mounho
B J
BJ
The University of New Mexico College of Pharmacy, Toxicology Program, Albuquerque 87131-1066, USA.
Davila
D R
DR
Burchiel
S W
SW
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000097:blood / Q000633:toxicity; D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood / Q000633:toxicity*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D002118:Calcium