Selective exposure and analysis of the sheep tracheal lobe as a model for toxicological studies of respirable particles

Our plain-English summary of Selective exposure and analysis of the sheep tracheal lobe as a model for toxicological studies of respirable particles, by R. Bégin, S. Massé, M. Rola-Pleszczynski, et al (Environmental Research, 1985).

The study

• Authors: R. Bégin, S. Massé, M. Rola-Pleszczynski, G. Drapeau, D. Dalle
• Journal: Environmental Research
• Published: 1985;36(2):389-404
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A conscious sheep model, recently developed to study sequentially the bronchoalveolar milieu, was further refined to use in the rapid in vivo assessment of the biological effects of respirable particles. In this model, the anatomically isolated tracheal lobe was selectively exposed to either 100 ml phosphate buffered saline (PBS) (control group of 12 sheep), 100 mg of 0.1-micron latex beads in 100 ml PBS (latex group of 12 sheep), or 100 mg of UICC Canadian chrysotile fibers in 100 ml PBS (asbestos group of 12 sheep). Bronchoalveolar lavages (BAL) of the tracheal lobe were obtained prior to exposure and at Days 1, 8, 15, 21, 29, 45, and 60 after exposure. Whole-lung detailed pulmonary function tests (PFT) were performed at the same times and the histopathology of the lobe was examined in six sheep in each group at Days 29 and 60. In the control sheep, there were no significant changes over time in any of the measures, and lung morphology remained normal. In the latex group, there was no significant change in PFT, the BAL analyses documented early transient increase in cellularity (macrophages and neutrophils at Day 1) and only macrophages after; lung histology documented an early macrophagic alveolitis which decreased to less than 10% of the initial inflammatory reaction at Day 60, without other distortion of the lung and airway architecture. In the asbestos sheep, the only change in whole-lung PFT was a 10-torr fall in arterial O2 pressure. BAL analyses documented persistent increases in macrophages, neutrophils, and lactate dehydrogenase as well as increasing gamma-globulins. Lung histology revealed a macrophagic and neutrophilic peribronchiolar alveolitis at Day 30, which regressed substantially by Day 60, but persistent peribronchiolar alveolitis, early fibrosis, and severe distortion of the small airways, lesions comparable to those of early asbestosis in sheep or humans. Thus selective exposure and sequential analyses of the sheep tracheal lobe in terms of BAL histomorphology should be valuable for rapid in vivo assessment of toxicity of respirable particles.

In plain English

In this animal experiment, 36 male sheep were divided into three groups of 12. One lung lobe (the tracheal lobe) received salt solution (controls), 100 mg of latex beads, or 100 mg of UICC Canadian chrysotile asbestos fibers. Lavage (lung-washing) fluid and lung function were checked repeatedly up to Day 60. Six sheep per group were killed for tissue examination at Days 29 and 60. Controls showed no significant changes. In latex sheep, lavage cells rose to 8 times control at Day 1, and residual inflammation covered less than 10% of the lobe by Day 60. In asbestos sheep, neutrophils were still 20 times control levels at Day 60, and the enzyme LDH stayed at an average of 4 times control. Arterial oxygen pressure fell by an average 10 torr, the only whole-lung function change. By Day 60 their inflammation had shrunk to about 20% of its initial extent, but small airways remained severely distorted. The authors called these lesions comparable to early asbestosis in sheep or humans. The authors concluded the model should be useful in predicting the toxicity and fibrosis-causing potential of industrial materials, but said its sensitivity needs further study.

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: Controlled animal experiment comparing three groups of sheep given saline, latex beads, or chrysotile asbestos into one lung lobe, followed with repeated lavage and lung function tests and later tissue examination
• Who was studied: 36 male sheep weighing 25 to 45 kg, at the pulmonary research unit of the Université de Sherbrooke, Quebec, Canada; 12 per group, with six per group examined by histology at Day 29 and six at Day 60
• Exposure: A single infusion into the tracheal lobe, through a bronchoscope, of 100 mg UICC Canadian chrysotile asbestos fibers in 100 ml phosphate buffered saline (asbestos group). The comparison groups received 100 mg of 0.1-micrometer latex beads in 100 ml saline (latex group) or 100 ml saline alone (control group).
• Main results:
  • In the control sheep, there were no significant changes over time in any measure, and lung tissue remained normal
  • Latex group: total lavage cells rose at Day 1 to 8 times the control value (P < 0.001)
  • Asbestos group: between Days 8 and 29, neutrophils averaged 34% of total lavage cells, or 100 times control levels. At Day 60 they were still 20 times above levels in control or latex sheep (P < 0.05).
  • Asbestos group: the enzyme LDH in lavage fluid increased significantly and persistently, to an average 4 times control levels
  • Asbestos group: total proteins in lavage fluid rose gradually, largely due to gamma-globulins, which became significant at Day 22 and after
  • Whole-lung mechanical function tests: no significant changes over time and no significant differences between the three groups
  • Asbestos group: arterial oxygen pressure decreased by an average 10 torr, and this mild hypoxemia persisted through the 60 days after exposure
  • Latex group: by Day 60 the macrophage infiltrate had largely regressed, and residual cell accumulation made up less than 10% of the lobe
  • Asbestos group, Day 30: a macrophage and neutrophil infiltrate with considerable distortion of lung and airway architecture
  • Asbestos group, Day 60: the infiltrate had regressed to about 20% of its initial extent, mainly around the small airways, with persistent severe distortion of the small airways
  • The authors described the asbestos-group lesions (persistent alveolitis, early fibrosis and small-airway distortion) as comparable to early asbestosis in sheep or humans
• The authors' conclusion: The authors concluded that the sheep tracheal lobe model should be useful in predicting the cytotoxicity and fibrogenicity of various materials used in industry
• Limitations the authors state:
  • The study needs to be pursued further regarding the sensitivity of the model and the specificity of the biological markers
  • The sheep model is more expensive to use than small-rodent models
  • The early inflammatory reaction appears to have limited specificity

Topics

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

Medical terms in this study, explained in our Lexicon: UICC, Chrysotile, Bronchoalveolar Lavage (BAL), Pulmonary Function Test (PFT), Histopathology, Macrophage, Histology, Lactate Dehydrogenase (LDH).

Related studies

• Asbestos-induced lung injury in the sheep model: the initial alveolitis — R. Bégin, M. Rola-Pleszczynski, et al. (1983)
• Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests — R. Bégin, M. Rola-Pleszczynski, et al. (1983)
• Morphologic features and function of the airways in early asbestosis in the sheep model — R. Bégin, S. Massé, et al. (1982)
• Fibronectin and procollagen 3 levels in bronchoalveolar lavage of asbestos-exposed human subjects and sheep — R. Bégin, M. Martel, et al. (1986)
• Effect of mineral particles containing iron on primary cultures of rabbit tracheal epithelial cells: possible implication of oxidative stress — C. Guilianelli, A. Baeza-Squiban, et al. (1993)
• Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells — B. Keeling, K.Y. Li, et al. (1994)

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