Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone
- Duke University Medical Center, Durham, NC (United States)
Electron microscopic morphometry was used to study the development of lung injury during and after chronic (78 weeks) exposure to a pattern of ozone (O3) designed to simulate high urban ambient concentrations that occur in some environments. The daily exposure regimen consisted of a 13-hr background of 0.06 ppm, an exposure peak that rose from 0.06 to 0.25 ppm, and returned to the background level over a 9-hr period, and 2-hr downtime for maintenance. Rats were exposed for 1, 3, 13, and 78 weeks. Additional groups of rats exposed for 13 or 78 weeks were allowed to recover in filtered clean air for 6 or 17 weeks, respectively. Rats exposed to filtered air for the same lengths of time were used as controls. Samples from proximal alveolar regions and terminal bronchioles were obtained by microdissection. Analysis of the proximal alveolar region revealed a biphasic response. Acute tissue reactions after 1 week of exposure included epithelial inflammation, interstitial edema, interstitial cell hypertrophy, and influx of macrophages. These responses subsided after 3 weeks of exposure. Progressive epithelial and interstitial tissue responses developed with prolonged exposure and included epithelial hyperplasia, fibroblast proliferation, and interstitial matrix accumulation. The epithelial responses involved both type I and type II epithelial cells. Alveolar type I cells increased in number, became thicker, and covered a smaller average surface area. These changes persisted throughout the entire exposure and did not change during the recovery period, indicating the sensitivity of these cells to injury. The main response of type II epithelial cells was cell proliferation. The accumulation of interstitial matrix after chronic exposure consisted of deposition of both increased amounts of basement membrane and collagen fibers.
- OSTI ID:
- 7159257
- Journal Information:
- Toxicology and Applied Pharmacology; (United States), Vol. 115:2; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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LUNGS
SENSITIVITY
OZONE
TOXICITY
AIR POLLUTION
CHRONIC EXPOSURE
ELECTRON MICROSCOPY
ENVIRONMENTAL EXPOSURE
EPITHELIUM
FIBROSIS
INHALATION
MACROPHAGES
RATS
SIMULATION
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BODY
CONNECTIVE TISSUE CELLS
INTAKE
MAMMALS
MICROSCOPY
ORGANS
PATHOLOGICAL CHANGES
PHAGOCYTES
POLLUTION
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology