Early postnatal, but not late, exposure to chemical ambient pollutant 1,2-naphthoquinone increases susceptibility to pulmonary allergic inflammation at adulthood

• Published in: Archives of toxicology 2014-08, Vol.88 (8), p.1589-1605
• Main Authors: Santos, Karen T., Florenzano, Juliana, Rodrigues, Leandro, Fávaro, Rodolfo R., Ventura, Fernanda F., Ribeiro, Marcela G., Teixeira, Simone A., Ferreira, Heloisa H. A., Brain, Susan D., Damazo, Amílcar S., Zorn, Telma M., Câmara, Niels O., Muscará, Marcelo N., Peron, Jean Pierre, Costa, Soraia K.
• Format: Article
• Language: English
• Subjects: Adaptive Immunity - drug effects; Aging - drug effects; Aging - immunology; Air Pollutants - toxicity; Airborne particulates; Allergies; Animals; Animals, Newborn; Biomedical and Life Sciences; Biomedicine; Cytokines; Cytokines - immunology; Diesel fuels; Disease Susceptibility - chemically induced; Environmental Health; Human exposure; Immunity, Innate - drug effects; Immunoglobulin E - immunology; In Vitro Systems; Inhalation Exposure - adverse effects; Inhalation Exposure - analysis; Leukotriene B4 - immunology; Male; Naphthoquinones - toxicity; Occupational Medicine/Industrial Medicine; Ovalbumin - immunology; Pharmacology/Toxicology; Pneumonia - chemically induced; Pneumonia - immunology; Respiratory Hypersensitivity - chemically induced; Respiratory Hypersensitivity - immunology; Toxicity; Vehicle Emissions - analysis; Vehicle Emissions - toxicity
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-014-1212-z

High diesel exhaust particle levels are associated with increased health effects; however, knowledge on the impact of its chemical contaminant 1,2-naphthoquinone (1,2-NQ) is limited. We investigated whether postnatal and adult exposures to 1,2-NQ influence allergic reaction and the roles of innate and adaptive immunity. Male neonate (6 days) and adult (56 days) C57Bl/6 mice were exposed to 1,2-NQ (100 nM; 15 min) for 3 days, and on day 59, they were sensitized and later challenged with ovalbumin (OVA). Airway hyper-responsiveness (AHR) and production of cytokines, immunoglobulin E (IgE) and leukotriene B 4 (LTB 4 ) were measured in the airways. Postnatal exposure to 1,2-NQ activated dendritic cells in splenocytes by increasing expressing cell surface molecules (e.g., CD11c). Co-exposure to OVA effectively polarized T helper (Th) type 2 (Th2) by secreting Th2-mediated cytokines. Re-stimulation with unspecific stimuli (PMA and ionomycin) generated a mixed Th1 (CD4 + /IFN-γ + ) and Th17 (CD4 + /IL-17 + ) phenotype in comparison with the vehicle-matched group. Postnatal exposure to 1,2-NQ did not induce eosinophilia in the airways at adulthood, although it evoked neutrophilia and exacerbated OVA-induced eosinophilia, Th2 cytokines, IgE and LTB 4 production without affecting AHR and mast cell degranulation. At adulthood, 1,2-NQ exposure evoked neutrophilia and increased Th1/Th2 cytokine levels, but failed to affect OVA-induced eosinophilia. In conclusion, postnatal exposure to 1,2-NQ increases the susceptibility to antigen-induced asthma. The mechanism appears to be dependent on increased expression of co-stimulatory molecules, which leads to cell presentation amplification, Th2 polarization and enhanced LTB 4 , humoral response and Th1/Th2 cytokines. These findings may be useful for future investigations on treatments focused on pulmonary illnesses observed in children living in heavy polluted areas.