Dose-Dependent Tolerance to Ozone. III. Elevation of Intracellular Clara Cell 10-kDa Protein in Central Acini of Rats Exposed for 20 Months

D. E. Dodge, R. B. Rucker, Kent E Pinkerton, C. J. Haselton, Charles Plopper

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Abstract

Understanding factors that promote pulmonary tolerance to long-term oxidant injury is essential to evaluating health risks in humans. One such factor may be Clara cell 10-kDa protein (CC10), a protein secreted by nonciliated cells in distal conducting airways thought to have an anti-inflammatory action against inhaled xenobiotics. Using standard immunohistochemical techniques and laser scanning confocal microscopy, we assessed changes in CC10 abundance in the centriacinar region of the rat following 20 months′ exposure to 0.12 and 1.00 ppm ozone. Three zones of reflectance intensity (high, medium, and low), directly related to CC10 density, were used to distinguish between the two major subcellular compartments where CC10 is distributed: granules and endoplasmic reticulum. Low levels of ozone (0.12 ppm) had no significant effect on the cellular distribution or abundance of CC10 in nonciliated epithelium in the centriacinar region. In contrast, 1.00 ppm ozone not only elevated cellular volume of granule-based CC10, but also elevated the protein′s concentration within the granules and increased the number of granules per cell profile. The proportion of nonciliated cells in terminal bronchioles increased significantly at the expense of ciliated cells. This combination of factors led to a threefold increase in CC10 stored per unit surface area of epithelium in terminal bronchioles. The nonciliated cells in ozone-induced respiratory bronchioles contained a distribution of CC10 similar to that of bronchiolar nonciliated cells in control animals. We conclude that ozone-induced tolerance may be related to the increased abundance and wider distribution of CC10 in central acini of rats following long-term ozone exposure.

Original languageEnglish (US)
Pages (from-to)109-123
Number of pages15
JournalToxicology and Applied Pharmacology
Volume127
Issue number1
DOIs
StatePublished - Jul 1994

Fingerprint

Ozone
Rats
Proteins
Bronchioles
Confocal microscopy
Epithelium
Health risks
Xenobiotics
Oxidants
Animals
Anti-Inflammatory Agents
Confocal Microscopy
Endoplasmic Reticulum
Scanning

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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Dose-Dependent Tolerance to Ozone. III. Elevation of Intracellular Clara Cell 10-kDa Protein in Central Acini of Rats Exposed for 20 Months. / Dodge, D. E.; Rucker, R. B.; Pinkerton, Kent E; Haselton, C. J.; Plopper, Charles.

In: Toxicology and Applied Pharmacology, Vol. 127, No. 1, 07.1994, p. 109-123.

Research output: Contribution to journalArticle

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abstract = "Understanding factors that promote pulmonary tolerance to long-term oxidant injury is essential to evaluating health risks in humans. One such factor may be Clara cell 10-kDa protein (CC10), a protein secreted by nonciliated cells in distal conducting airways thought to have an anti-inflammatory action against inhaled xenobiotics. Using standard immunohistochemical techniques and laser scanning confocal microscopy, we assessed changes in CC10 abundance in the centriacinar region of the rat following 20 months′ exposure to 0.12 and 1.00 ppm ozone. Three zones of reflectance intensity (high, medium, and low), directly related to CC10 density, were used to distinguish between the two major subcellular compartments where CC10 is distributed: granules and endoplasmic reticulum. Low levels of ozone (0.12 ppm) had no significant effect on the cellular distribution or abundance of CC10 in nonciliated epithelium in the centriacinar region. In contrast, 1.00 ppm ozone not only elevated cellular volume of granule-based CC10, but also elevated the protein′s concentration within the granules and increased the number of granules per cell profile. The proportion of nonciliated cells in terminal bronchioles increased significantly at the expense of ciliated cells. This combination of factors led to a threefold increase in CC10 stored per unit surface area of epithelium in terminal bronchioles. The nonciliated cells in ozone-induced respiratory bronchioles contained a distribution of CC10 similar to that of bronchiolar nonciliated cells in control animals. We conclude that ozone-induced tolerance may be related to the increased abundance and wider distribution of CC10 in central acini of rats following long-term ozone exposure.",
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