title: Postnatal exposure history and airways: oxidant stress responses in airway explants.
abstract: Postnatally, the lung continues to grow and differentiate while interacting with the environment. Exposure to ozone (O(3)) and allergens during postnatal lung development alters structural elements of conducting airways, including innervation and neurokinin abundance. These changes have been linked with development of asthma in a rhesus monkey model. We hypothesized that O(3) exposure resets the ability of the airways to respond to oxidant stress and that this is mediated by changes in the neurokinin-1 receptor (NK-1R). Infant rhesus monkeys received episodic exposure to O(3) biweekly with or without house dust mite antigen (HDMA) from 6 to 12 months of age. Age-matched monkeys were exposed to filtered air (FA). Microdissected airway explants from midlevel airways (intrapulmonary generations 5-8) for four to six animals in each of four groups (FA, O(3), HDMA, and HDMA+O(3)) were tested for NK-1R gene responses to acute oxidant stress using exposure to hydrogen peroxide (1.2 mM), a lipid ozonide (10 μM), or sham treatment for 4 hours in vitro. Airway responses were measured using real-time quantitative RT-PCR of NK-1R and IL-8 gene expression. Basal NK-1R gene expression levels were not different between the exposure groups. Treatment with ozonide or hydrogen peroxide did not change NK-1R gene expression in animals exposed to FA, HDMA, or HDMA+O(3). However, treatment in vitro with lipid ozonide significantly increased NK-1R gene expression in explants from O(3)-exposed animals. We conclude that a history of prior O(3) exposure resets the steady state of the airways to increase the NK-1R response to subsequent acute oxidant stresses.
authors.affiliation: Center for Health and the Environment, University of California Davis, Davis, CA 95616-8732, USA.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Murphy
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Edwards
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Miller
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Hyde
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D015870:Gene Expression; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008253:Macaca mulatta; D008297:Male; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010126:Ozone / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: C503429:1,2,4-trioxane; D039741:Antigens, Dermatophagoides; D006571:Heterocyclic Compounds; D016209:Interleukin-8; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016877:Oxidants; D018040:Receptors, Neurokinin-1; D010126:Ozone; D006861:Hydrogen Peroxide