title: Bronchiolarized metaplasia and interstitial fibrosis in rat lungs chronically exposed to high ambient levels of ozone.
abstract: The cellular and tissue changes in the lungs of rats were studied using electron microscopy following 20 months exposure to a range of ozone levels from 0.12 to 1.0 ppm. Male and female Fischer 344 rats were exposed and morphometric methods were used to determine the volume, surface area, and cellular changes observed in bronchiole-alveolar duct regions following chronic ozone exposure. No major gender-related effects were observed in response to chronic inhalation of ozone nor were significant effects of ozone exposure found in either terminal bronchioles or the proximal alveolar regions in animals chronically exposed to 0.12 ppm ozone. The proximal alveolar regions of animals exposed for 20 months to 0.5 and 1.0 ppm ozone were significantly altered with exposure. The high-dose, long-term exposure to ozone resulted in a pronounced increase in volume of both the interstitium and epithelium in the proximal alveolar regions. The thickening of the epithelium was due to a change in tissue type from the normal squamous epithelium to a cuboidal epithelium similar, but not identical, to that found in terminal bronchioles. This bronchiolar epithelial metaplasia of proximal alveolar ducts, which was dose related, was composed of differentiated ciliated and Clara cells similar to those found in terminal bronchioles. In addition, unique cells which contained morphologic features of many different cell types were observed. These cells, which may represent stem cells or differentiated but transformed cells, were found associated with the bronchiolar metaplasia of alveolar ducts. In conjunction with the epithelial changes, cellular and matrix components in the interstitium were increased with chronic exposure to 0.5 and 1.0 ppm ozone. All matrix components were increased including collagen, elastin, and basement membrane, as well as other acellular spaces which did not contain identifiable structures. The total volume of interstitial fibroblasts was also increased in the high-dose exposure group. Alveolar macrophages were increased only in the 1.0 ppm exposed animals. The cell and tissue changes in the terminal bronchioles were less pronounced indicating a relative resistance of this tissue to ozone and mainly consisted of a change in cell type from ciliated to Clara cells in the 1.0 ppm exposed animals. The relative resistance of bronchiolar tissue to high concentration ozone exposure and the extensive bronchiolar epithelial metaplasia may be an adaptive mechanism following chronic ozone exposure.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Stockstill
authors.forename: L Y
authors.initials: LY
authors.lastname: Chang
authors.forename: M G
authors.initials: MG
authors.lastname: Ménache
authors.forename: P W
authors.initials: PW
authors.lastname: Mellick
authors.forename: R R
authors.initials: RR
authors.lastname: Mercer
authors.forename: J D
authors.initials: JD
authors.lastname: Crapo
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D008297:Male; D008679:Metaplasia; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
chemical_list: D010083:Oxidants, Photochemical; D010126:Ozone