title: Polycyclic aromatic hydrocarbons inhibit differentiation of human monocytes into macrophages.
abstract: Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are ubiquitous environmental carcinogenic contaminants exerting deleterious effects toward cells acting in the immune defense such as monocytic cells. To investigate the cellular basis involved, we have examined the consequences of PAH exposure on macrophagic differentiation of human blood monocytes. Treatment by BP markedly inhibited the formation of adherent macrophagic cells deriving from monocytes upon the action of either GM-CSF or M-CSF. Moreover, it reduced expression of macrophagic phenotypic markers such as CD71 and CD64 in GM-CSF-treated monocytic cells, without altering cell viability or inducing an apoptotic process. Exposure to BP also strongly altered functional properties characterizing macrophagic cells such as endocytosis, phagocytosis, LPS-triggered production of TNF-alpha and stimulation of allogeneic lymphocyte proliferation. Moreover, formation of adherent macrophagic cells was decreased in response to PAHs distinct from BP such as dimethylbenz(a)anthracene and 3-methylcholanthrene, which interact, like BP, with the arylhydrocarbon receptor (AhR) known to mediate many PAH effects. In contrast, benzo(e)pyrene, a PAH not activating AhR, had no effect. In addition, AhR was demonstrated to be present and functional in cultured monocytic cells, and the use of its antagonist alpha-naphtoflavone counteracted inhibitory effects of BP toward macrophagic differentiation. Overall, these data demonstrate that exposure to PAHs inhibits functional in vitro differentiation of blood monocytes into macrophages, likely through an AhR-dependent mechanism. Such an effect may contribute to the immunotoxicity of these environmental carcinogens owing to the crucial role played by macrophages in the immune defense.
authors.affiliation: Faculté de Pharmacie, Institut National de la Santé et de la Recherche Médicale, Rennes, France.
authors.forename: Julien
authors.initials: J
authors.lastname: van Grevenynghe
authors.forename: Sophie
authors.initials: S
authors.lastname: Rion
authors.forename: Eric
authors.initials: E
authors.lastname: Le Ferrec
authors.forename: Marc
authors.initials: M
authors.lastname: Le Vee
authors.forename: Laurence
authors.initials: L
authors.lastname: Amiot
authors.forename: Renée
authors.initials: R
authors.lastname: Fauchet
authors.forename: Olivier
authors.initials: O
authors.lastname: Fardel
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D011084:Polycyclic Aromatic Hydrocarbons / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D000954:Antigens, Surface; D001571:Benzoflavones; D015415:Biomarkers; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; C011512:alpha-naphthoflavone; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor