Polycyclic aromatic hydrocarbons affect functional differentiation and maturation of human monocyte-derived dendritic cells.
Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are environmental carcinogens exhibiting potent immunosuppressive properties. To determine the cellular bases of this immunotoxicity, we have studied the effects of PAHs on differentiation, maturation, and function of monocyte-derived dendritic cells (DC). Exposure to BP during monocyte differentiation into DC upon the action of GM-CSF and IL-4 markedly inhibited the up-regulation of markers found in DC such as CD1a, CD80, and CD40, without altering cell viability. Besides BP, PAHs such as dimethylbenz(a)anthracene and benzanthracene also strongly altered CD1a levels. Moreover, DC generated in the presence of BP displayed decreased endocytic activity. Features of LPS-mediated maturation of DC, such as CD83 up-regulation and IL-12 secretion, were also impaired in response to BP treatment. BP-exposed DC poorly stimulated T cell proliferation in mixed leukocyte reactions compared with their untreated counterparts. In contrast to BP, the halogenated arylhydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, which shares some features with PAHs, including interaction with the arylhydrocarbon receptor, failed to phenotypically alter differentiation of monocytes into DC, suggesting that binding to the arylhydrocarbon receptor cannot mimic PAH effects on DC. Overall, these data demonstrate that exposure to PAHs inhibits in vitro functional differentiation and maturation of blood monocyte-derived DC. Such an effect may contribute to the immunotoxicity of these environmental contaminants due to the major role that DC play as potent APC in the development of the immune response.
Laupeze
Béatrice
B
Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, Unité Propre de Recherche de l'Enseignement Supérieur 22-33, Faculté de Médecine, Rennes, France.
Amiot
Laurence
L
Sparfel
Lydie
L
Le Ferrec
Eric
E
Fauchet
Renée
R
Fardel
Olivier
O
D001564:Benzo(a)pyrene / Q000633:toxicity; D002274:Carcinogens, Environmental / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000633:toxicity*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology
D002274:Carcinogens, Environmental; D007166:Immunosuppressive Agents; D000072317:Polychlorinated Dibenzodioxins; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene