title: Structural and functional localization of airway effects from episodic exposure of infant monkeys to allergen and/or ozone.
abstract: Both allergen and ozone exposure increase asthma symptoms and airway responsiveness in children. Little is known about how these inhalants may differentially modify airway responsiveness in large proximal as compared to small distal airways. We evaluated whether bronchi and respiratory bronchioles from infant monkeys exposed episodically to allergen and/or ozone differentially develop intrinsic hyperresponsiveness to methacholine and whether eosinophils and/or pulmonary neuroendocrine cells play a role. Infant monkeys were exposed episodically for 5 months to: (1) filtered air, (2) aerosolized house dust mite allergen, (3) ozone 0.5 ppm, or (4) house dust mite allergen + ozone. Studying the function/structure relationship of the same lung slices, we evaluated methacholine airway responsiveness and histology of bronchi and respiratory bronchioles. In bronchi, intrinsic responsiveness was increased by allergen exposure, an effect reduced by bombesin antagonist. In respiratory bronchioles, intrinsic airway responsiveness was increased by allergen + ozone exposure. Eosinophils were increased by allergen and allergen + ozone exposure in bronchi and by allergen exposure in respiratory bronchioles. In both airways, exposure to allergen + ozone resulted in fewer tissue eosinophils than did allergen exposure alone. In bronchi, but not in respiratory bronchioles, the number of eosinophils and neuroendocrine cells correlated with airway responsiveness. We conclude that episodically exposing infant monkeys to house dust mite allergen with or without ozone increased intrinsic airway responsiveness to methacholine in bronchi differently than in respiratory bronchioles. In bronchi, eosinophils and neuroendocrine cells may play a role in the development of airway hyperresponsiveness.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, Davis, 2516 Stockton Boulevard, Sacramento, CA 95817, USA. jesse.joad@ucdmc.ucdavis.edu
authors.forename: Jesse P
authors.initials: JP
authors.lastname: Joad
authors.forename: Kayleen S
authors.initials: KS
authors.lastname: Kott
authors.forename: John M
authors.initials: JM
authors.lastname: Bric
authors.forename: Janice L
authors.initials: JL
authors.lastname: Peake
authors.forename: Charles G
authors.initials: CG
authors.lastname: Plopper
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
authors.forename: Laurel J
authors.initials: LJ
authors.lastname: Gershwin
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
mesh_terms: D000403:Airway Resistance / Q000187:drug effects / Q000276:immunology; D000485:Allergens / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D004357:Drug Synergism; D004804:Eosinophils / Q000276:immunology; D019570:Inhalation Exposure; D007958:Leukocyte Count; D008253:Macaca mulatta; D016210:Methacholine Chloride / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D010126:Ozone / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D039981:Pyroglyphidae / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*
chemical_list: D000485:Allergens; D016210:Methacholine Chloride; D010126:Ozone