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

Abstract

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 B4 (LTB4) 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 LTB4 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 LTB4, 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.

• Authors: Karen T Santos, Juliana Florenzano, Leandro Rodrigues, Rodolfo R Fávaro, Fernanda F Ventura, Marcela G Ribeiro, Simone A Teixeira, Heloisa H A Ferreira, Susan D Brain, Amílcar S Damazo, Telma M Zorn, Niels O Câmara, Marcelo N Muscará, Jean Pierre Peron, Soraia K Costa
• Journal: Archives of toxicology (Arch Toxicol) Vol. 88 Issue 8 Pg. 1589-605 (Aug 2014) ISSN: 1432-0738 [Electronic] Germany
• PMID: 24554396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Air Pollutants
• Cytokines
• Naphthoquinones
• Vehicle Emissions
• Leukotriene B4
• Immunoglobulin E
• 1,2-naphthoquinone
• Ovalbumin

Topics

• Adaptive Immunity (drug effects)
• Aging (drug effects, immunology)
• Air Pollutants (toxicity)
• Animals
• Animals, Newborn
• Cytokines (immunology)
• Disease Susceptibility (chemically induced)
• Immunity, Innate (drug effects)
• Immunoglobulin E (immunology)
• Inhalation Exposure (adverse effects, analysis)
• Leukotriene B4 (immunology)
• Male
• Naphthoquinones (toxicity)
• Ovalbumin (immunology)
• Pneumonia (chemically induced, immunology)
• Respiratory Hypersensitivity (chemically induced, immunology)
• Vehicle Emissions (analysis, toxicity)