title: 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.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes, 1524, São Paulo, SP, 05508-900, Brazil.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Santos
authors.forename: Juliana
authors.initials: J
authors.lastname: Florenzano
authors.forename: Leandro
authors.initials: L
authors.lastname: Rodrigues
authors.forename: Rodolfo R
authors.initials: RR
authors.lastname: Fávaro
authors.forename: Fernanda F
authors.initials: FF
authors.lastname: Ventura
authors.forename: Marcela G
authors.initials: MG
authors.lastname: Ribeiro
authors.forename: Simone A
authors.initials: SA
authors.lastname: Teixeira
authors.forename: Heloisa H A
authors.initials: HH
authors.lastname: Ferreira
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
authors.forename: Amílcar S
authors.initials: AS
authors.lastname: Damazo
authors.forename: Telma M
authors.initials: TM
authors.lastname: Zorn
authors.forename: Niels O
authors.initials: NO
authors.lastname: Câmara
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Muscará
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Peron
authors.forename: Soraia K
authors.initials: SK
authors.lastname: Costa
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000375:Aging / Q000187:drug effects / Q000276:immunology*; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000276:immunology; D004198:Disease Susceptibility / Q000139:chemically induced; D007113:Immunity, Innate / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology; D019570:Inhalation Exposure / Q000009:adverse effects* / Q000032:analysis; D007975:Leukotriene B4 / Q000276:immunology; D008297:Male; D009285:Naphthoquinones / Q000633:toxicity*; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D009285:Naphthoquinones; D001335:Vehicle Emissions; D007975:Leukotriene B4; D007073:Immunoglobulin E; C040756:1,2-naphthoquinone; D010047:Ovalbumin