Relationship of inhaled ozone concentration to acute tracheobronchial epithelial injury, site-specific ozone dose, and glutathione depletion in rhesus monkeys

Charles G. Plopper, Gary E. Hatch, Viviana Wong, Xiuchen Duan, Alison J. Weir, Brian K. Tarkington, Robert B. Devlin, Suzanne Becker, A. R. Buckpitt

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Abstract

Acute pulmonary epithelial injury produced by short-term exposure to ozone varies by site within the tracheobronchial tree. To test whether this variability is related to the local dose of ozone at the tissue site or to local concentrations of glutathione, we exposed adult male rhesus monkeys for 2 h to filtered air or to 0.4 or 1.0 ppm ozone generated from 18O2. Following exposure, lungs were split into lobes and specimens were selected by microdissection so that measurements could be made on airway tissue of similar branching history, including trachea, proximal (generation one or two) and distal (generation six or seven) intrapulmonary bronchi, and proximal respiratory bronchioles. One half of the lung was lavaged for analysis of extracellular components. In monkeys exposed to filtered air, the concentration of reduced glutathione (GSH) varied throughout the airway tree, with the proximal intrapulmonary bronchus having the lowest concentration and the parenchyma having the highest concentration. Exposure to 1.0 ppm ozone significantly reduced GSH only in the respiratory bronchiole, whereas exposure to 0.4 ppm increased GSH only in the proximal intrapulmonary bronchus. Local ozone dose (measured as excess 18O) varied by as much as a factor of three in different airways of monkeys exposed to 1.0 ppm, with respiratory bronchioles having the highest concentration and the parenchyma the lowest concentration. In monkeys exposed to 0.4 ppm, the ozone dose was 60% to 70% less than in the same site in monkeys exposed to 1.0 ppm. Epithelial disruption was present to some degree in all airway sites, but not in the parenchyma, in animals exposed to 1.0 ppm ozone. The mass of mucous and ciliated cells decreased in all airways, and necrotic and inflammatory cells increased. At 0.4 ppm, epithelial injury was minimal, except in the respiratory bronchiole, where cell loss and necrosis occurred, and was 50% that found in monkeys exposed to 1.0 ppm ozone. We conclude that there is a close association between site-specific O3 dose, the degree of epithelial injury, and glutathione depletion at local sites in the tracheobronchial tree. Plopper, C. G., G. E. Hatch, V. Wong, X. Duan, A. J. Weir, B. K. Tarkington, R. B. Devlin, S. Becker, and A. R. Buckpitt. 1998. Relationship of inhaled ozone concentration to acute tracheobronchial epithelial injury, site-specific ozone dose, and glutathione depletion in rhesus monkeys. Am. J. Respir. Cell Mol. Biol. 19:387-399.

Original languageEnglish (US)
Pages (from-to)387-399
Number of pages13
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume19
Issue number3
StatePublished - 1998

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Ozone
Macaca mulatta
Glutathione
Wounds and Injuries
Bronchioles
Haplorhini
Bronchi
Microdissection
Air
Tissue
Lung
Acute Lung Injury
Trachea
Animals
Necrosis
History

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Relationship of inhaled ozone concentration to acute tracheobronchial epithelial injury, site-specific ozone dose, and glutathione depletion in rhesus monkeys. / Plopper, Charles G.; Hatch, Gary E.; Wong, Viviana; Duan, Xiuchen; Weir, Alison J.; Tarkington, Brian K.; Devlin, Robert B.; Becker, Suzanne; Buckpitt, A. R.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 19, No. 3, 1998, p. 387-399.

Research output: Contribution to journalArticle

Plopper, Charles G. ; Hatch, Gary E. ; Wong, Viviana ; Duan, Xiuchen ; Weir, Alison J. ; Tarkington, Brian K. ; Devlin, Robert B. ; Becker, Suzanne ; Buckpitt, A. R. / Relationship of inhaled ozone concentration to acute tracheobronchial epithelial injury, site-specific ozone dose, and glutathione depletion in rhesus monkeys. In: American Journal of Respiratory Cell and Molecular Biology. 1998 ; Vol. 19, No. 3. pp. 387-399.
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AU - Hatch, Gary E.

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N2 - Acute pulmonary epithelial injury produced by short-term exposure to ozone varies by site within the tracheobronchial tree. To test whether this variability is related to the local dose of ozone at the tissue site or to local concentrations of glutathione, we exposed adult male rhesus monkeys for 2 h to filtered air or to 0.4 or 1.0 ppm ozone generated from 18O2. Following exposure, lungs were split into lobes and specimens were selected by microdissection so that measurements could be made on airway tissue of similar branching history, including trachea, proximal (generation one or two) and distal (generation six or seven) intrapulmonary bronchi, and proximal respiratory bronchioles. One half of the lung was lavaged for analysis of extracellular components. In monkeys exposed to filtered air, the concentration of reduced glutathione (GSH) varied throughout the airway tree, with the proximal intrapulmonary bronchus having the lowest concentration and the parenchyma having the highest concentration. Exposure to 1.0 ppm ozone significantly reduced GSH only in the respiratory bronchiole, whereas exposure to 0.4 ppm increased GSH only in the proximal intrapulmonary bronchus. Local ozone dose (measured as excess 18O) varied by as much as a factor of three in different airways of monkeys exposed to 1.0 ppm, with respiratory bronchioles having the highest concentration and the parenchyma the lowest concentration. In monkeys exposed to 0.4 ppm, the ozone dose was 60% to 70% less than in the same site in monkeys exposed to 1.0 ppm. Epithelial disruption was present to some degree in all airway sites, but not in the parenchyma, in animals exposed to 1.0 ppm ozone. The mass of mucous and ciliated cells decreased in all airways, and necrotic and inflammatory cells increased. At 0.4 ppm, epithelial injury was minimal, except in the respiratory bronchiole, where cell loss and necrosis occurred, and was 50% that found in monkeys exposed to 1.0 ppm ozone. We conclude that there is a close association between site-specific O3 dose, the degree of epithelial injury, and glutathione depletion at local sites in the tracheobronchial tree. Plopper, C. G., G. E. Hatch, V. Wong, X. Duan, A. J. Weir, B. K. Tarkington, R. B. Devlin, S. Becker, and A. R. Buckpitt. 1998. Relationship of inhaled ozone concentration to acute tracheobronchial epithelial injury, site-specific ozone dose, and glutathione depletion in rhesus monkeys. Am. J. Respir. Cell Mol. Biol. 19:387-399.

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