title: Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys.
abstract: Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA. esschelegle@ucdavis.edu
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Miller
authors.forename: Laurel J
authors.initials: LJ
authors.lastname: Gershwin
authors.forename: Michelle V
authors.initials: MV
authors.lastname: Fanucchi
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
authors.forename: Joan E
authors.initials: JE
authors.lastname: Gerriets
authors.forename: William F
authors.initials: WF
authors.lastname: Walby
authors.forename: Valerie
authors.initials: V
authors.lastname: Mitchell
authors.forename: Brian K
authors.initials: BK
authors.lastname: Tarkington
authors.forename: Viviana J
authors.initials: VJ
authors.lastname: Wong
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Baker
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Pantle
authors.forename: Jesse P
authors.initials: JP
authors.lastname: Joad
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Reen
authors.initials: R
authors.lastname: Wu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Hyde
authors.forename: Charles G
authors.initials: CG
authors.lastname: Plopper
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004357:Drug Synergism; D004804:Eosinophils / Q000276:immunology; D006632:Histamine / Q000097:blood; D006969:Hypersensitivity, Immediate / Q000139:chemically induced / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology; D008253:Macaca mulatta; D008925:Mites / Q000276:immunology; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D015656:Respiratory Mechanics / Q000187:drug effects; D012882:Skin Tests; D013050:Spectrometry, Fluorescence
chemical_list: D000336:Aerosols; D000485:Allergens; D010083:Oxidants, Photochemical; D007073:Immunoglobulin E; D010126:Ozone; D006632:Histamine