Alveolar type II cell responses to chronic inhalation of chrysotile asbestos in rats

Our plain-English summary of Alveolar type II cell responses to chronic inhalation of chrysotile asbestos in rats, by K.E. Pinkerton, S.L. Young, E.K. Fram, et al (American Journal of Respiratory Cell and Molecular Biology, 1990).

The study

• Authors: K.E. Pinkerton, S.L. Young, E.K. Fram, J.D. Crapo
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1990;3(6):543-52
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The effects of chronic exposure to chrysotile asbestos on alveolar type II cells were examined in the lungs of Fischer 344 rats. Morphometric and three-dimensional analyses were used to characterize the alveolar type II cell and to determine the relationship of asbestos fiber localization to ultrastructural change in these cells. During the 2-yr period of study, type II cell number and volume increased to values more than 4 times those seen in controls. Ultrastructurally, cisternal dilations of the rough endoplasmic reticulum (RER) composed 12% of the total cell volume after 12 mo of exposure to asbestos and was still 15% of the total cell volume 1 yr after fiber exposure had ended compared to less than 1% in control cells. Asbestos fiber density surrounding these cells was directly proportional to the degree of cisternal dilatation in the cell; however, lamellar body volume and number in these cells were not different from that found in control type II cells. The incidence of a subset of type II cells with large lamellated inclusions was 10-fold greater in regions near bronchiolar-alveolar duct junctions, compared to more distal gas exchange regions of the lungs. Normal-sized lamellar bodies were fused to these large lamellated inclusions. These cells also contained significantly greater numbers of lamellar bodies and multivesicular bodies than those type II cells in more distal lung regions. These ultrastructural changes observed in type II cells may be a simple dose response to inhaled asbestos or the manifestation of two distinct populations of cells in the lungs that respond to asbestos in different ways. Asbestos fiber dose, cellular microenvironment, and aberrations of the cell plasma membrane and/or cell cytoskeleton (i.e., microtubules and filaments) are discussed as potential factors in the changes noted in type II cells.

In plain English

In this animal experiment, 40 male Fischer 344 rats breathed chrysotile asbestos for 7 hours a day, 5 days a week for 12 months, averaging 11.4 mg/m3. Another 40 control rats breathed filtered air. Four rats per group were examined after 3 and 12 months of exposure and 1 year after it ended. After 12 months, total alveolar type II cell volume was 156 mm3 in exposed rats versus 30 mm3 in controls. Dilated channels of the rough endoplasmic reticulum made up 12% of cell volume at 12 months. One year after exposure ended they made up 15%, versus 0.2% in controls. In five cells reconstructed in three dimensions, this dilation rose with nearby fiber density, though no fiber was fully inside any cell. The authors said it is unknown whether this is cause and effect. At 12 months of exposure, cell profiles with large lamellated inclusions were 10 times as frequent within 1 mm of terminal bronchioles as in randomly sampled regions (farther away or of undetermined distance). The authors concluded that prolonged exposure produced persistent changes in these cells.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal inhalation experiment in rats, using morphometric (measurement-based) analysis and three-dimensional serial-section reconstruction of lung cells
• Who was studied: 40 male specific pathogen-free Fischer 344 rats aged 6 to 8 weeks were exposed to asbestos, and 40 controls were exposed to filtered air. At each time point (3 and 12 months of exposure, and 1 year after exposure ended), four exposed animals and four age-matched controls were randomly selected for study. Serial sections came from three animals exposed for 12 months and one age-matched control.
• Exposure: Aerosolized chrysotile asbestos (NIEHS Intermediate-Range chrysotile from the Jeffrey Mine, Quebec, Canada) for 7 hours per day, 5 days per week for 12 months. Chamber concentration averaged 11.4 plus or minus 2.2 mg/m3 (SD). Controls breathed filtered air only.
• Main results:
  • After 3 months of exposure, exposed rats had 127 million type II cells in the lungs, compared with 81 million in controls.
  • After 12 months of exposure, exposed rats had 220 million type II cells per both lungs. Their total cell volume was 156 mm3, compared with 30 mm3 in control lungs.
  • One year after exposure ended, exposed rats had 124 million type II cells, compared with 57 million in controls.
  • In exposed rats after 12 months, the cisternal space of the rough endoplasmic reticulum (RER) increased to 12% of total type II cell volume.
  • One year after the end of exposure, RER cisternae made up 15% of type II cell volume in exposed rats, compared with 0.2% in matched controls.
  • The lamellar body volume fraction fell in exposed rats, but the average volume of lamellar bodies per cell was not significantly different from controls.
  • In type II cells with dilated RER cisternae, asbestos fiber density within 2 micrometers of the cell was correlated with the degree of RER dilatation (p less than 0.05). The figure legend states that this was based on five reconstructed cells after 12 months of exposure.
  • Numerous asbestos fibers lay close to every reconstructed type II cell in exposed animals, but no fiber was found completely inside any cell.
  • In exposed rats after 12 months, type II cell profiles with a large inclusion body were 10 times more frequent in proximal regions (within 1 mm of terminal bronchioles) than in random lung regions (more than 1 mm away, or at a distance that could not be determined on a single section).
  • Type II cells with large lamellated inclusions (from exposed rats) had twice as many lamellar bodies as control type II cells and significantly more multivesicular bodies.
• The authors' conclusion: The authors concluded that prolonged exposure to chrysotile asbestos resulted in large changes in type II cell number, volume and size, along with persistent ultrastructural changes in type II cells in all regions of the lung parenchyma. They suggested that two morphologically distinct populations of type II cells may differ in function.
• Limitations the authors state:
  • The authors stated it is unknown whether the correlation between RER dilatation and surrounding fiber density is cause and effect or a nonspecific repair reaction.
  • Phospholipid biosynthesis and secretion were not measured in the exposed animals.
  • Only a small number of cells were reconstructed in three dimensions: five from controls and eight from exposed animals.
  • It was unclear whether the cell's filaments and microtubules were functioning normally after exposure.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile.

Related studies

• Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos — K.E. Pinkerton, P.C. Pratt, et al. (1984)
• Brief inhalation of asbestos compromises superoxide production in cells from bronchoalveolar lavage — J.M. Petruska, J. Marsh, et al. (1990)
• Up-regulated expression of transforming growth factor-alpha in the bronchiolar-alveolar duct regions of asbestos-exposed rats — J.Y. Liu, G.F. Morris, et al. (1996)
• Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats — T.W. Hesterberg, W.C. Miiller, et al. (1994)
• Silica binds serum proteins resulting in a shift of the dose-response for silica-induced chemokine expression in an alveolar type II cell line — E.G. Barrett, C. Johnston, et al. (1999)
• In vitro biodegradation of chrysotile fibres by alveolar macrophages and mesothelial cells in culture: comparison with a pH effect — M.C. Jaurand, A. Gaudichet, et al. (1984)

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