Halogenated aryl hydrocarbon-induced suppression of the in vitro plaque-forming cell response to sheep red blood cells is not dependent on the Ah receptor.
The immunosuppressive effects of the halogenated aromatic hydrocarbons (HAHs), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,9-PeCDF and 1,3,6,8-TCDF were investigated utilizing the Mishell-Dutton model for in vitro immunization. The selected polychlorinated dibenzofuran congeners and 2,3,7,8-TCDD caused a concentration-dependent suppression of the splenic plaque-forming cell response to sheep red blood cells using cell cultures derived from C57BL/6 (Ah responsive) mice. Previous studies showed that there was up to a 14,900-fold difference in the in vivo immunotoxicity of these compounds, however in the in vitro studies, their immunosuppressive potencies were comparable. In addition, these congeners also exhibited similar potencies using spleen cell cultures from DBA/2 (Ah-nonresponsive) mice. Previous research demonstrated that alpha-naphthoflavone was relatively inactive in the in vitro splenic assay system and that co-treatment of cells from C57BL/6 mice with alpha-naphthoflavone (10 microM) plus 2,3,7,8-TCDD (20 mM) resulted in a significant inhibition of the immunotoxicity of 2,3,7,8-TCDD. In these studies, comparable interactive effects were also observed in cells treated with alpha-naphthoflavone plus 1,3,6,8-TCDF, a weak in vivo Ah receptor agonist. Collectively, the results from this study suggest that there may be mechanism(s) of action for HAH-induced suppression of the in vitro murine humoral response to sheep red blood cells which are independent of the Ah receptor protein.
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University of New Mexico College of Pharmacy, Albuquerque.
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D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects* / Q000276:immunology; D001572:Benzofurans / Q000633:toxicity; D004912:Erythrocytes / Q000276:immunology; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects / Q000276:immunology; D012756:Sheep; D013329:Structure-Activity Relationship
D001572:Benzofurans; D006846:Hydrocarbons, Halogenated; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; C038890:2,3,4,7,8-pentachlorodibenzofuran; C014211:2,3,7,8-tetrachlorodibenzofuran