Polycyclic Aromatic Hydrocarbons Affect Functional Differentiation and Maturation of Human Monocyte-Derived Dendritic Cells

Abstract

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.

Biomonitoring of polycyclic aromatic hydrocarbon exposure in pregnant women in Trujillo, Peru — Comparison of different fuel types used for cooking

“…The increase in the metabolite concentrations during gestation may reflect an increase in exposure to PAHs, and may be important because of evidences that pre-natal exposure to PAH could influence birth outcomes and childhood mental development (Choi et al, 2008;Laupeze et al, 2002;Mishra et al, 2004). However, a study based on the collection of urine samples throughout the gestation period, and using a more effective method such as specific gravity adjustment for adjusting for urine dilution, is the only way to verify whether the observed increase represents actual changes in exposure across pregnancy stages.…”

“…The International Agency for Research on Cancer (IARC) classifies some of the individual PAHs as Class II carcinogens, and identifies benzo(a)pyrene as a Class I carcinogen (IARC, 2010;Straif et al, 2005). Additionally, PAHs have been associated with immunotoxicity (Laupeze et al, 2002;Oh et al, 2006).…”

Human Macrophages Constitute Targets for Immunotoxic Inorganic Arsenic

“…These monocytic cells were next cultured for 6 days in RPMI 1640 medium supplemented with 10% FCS, 2 mM L-glutamine, 20 UI/ml penicillin, and 20 g/ml streptomycin, in the presence of 800 UI/ml GM-CSF to get macrophages as previously reported (17)(18)(19). To obtain dendritic cells, monocytic cells were differentiated in the presence of 800 UI/ml GM-CSF and 500 UI/ml IL-4, as previously reported (20). Once differentiated, macrophages were cultured in GM-CSF-free RPMI 1640 medium in the absence or presence of As 2 O 3 for indicated time intervals.…”

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

“…PAHs that bind to and/or are activated by CYP are toxic to mouse and human stem cells (Fine et al, 1989;Murante & Gasiewicz, 2000;van Grevenynghe et al, 2005), and myeloid (Luster et al, 1985;Laupeze et al, 2002;van Grevenynghe et al, 2003) and lymphoid progenitors (Luster et al, 1988;Yamaguchi et al, 1997a,b;Near et al, 1999;Thurmond et al, 2000). Both DMBA and benzo [a]pyrene exert important effects on bone marrow that alter the formation of B cells.…”