Lung cell reactions in guinea pigs after inhalation of asbestos (amosite)

Our plain-English summary of Lung cell reactions in guinea pigs after inhalation of asbestos (amosite), by M. Sjöstrand, R. Rylander, R. Bergström (Toxicology, 1989).

The study

• Authors: M. Sjöstrand, R. Rylander, R. Bergström
• Journal: Toxicology
• Published: 1989;57(1):1-14
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To study the long-term effect of inhaled asbestos, guinea-pigs were exposed to airborne amosite at a concentration of 49 mg/m3, 2 h/day for 3 or 6 weeks and examined up to 2 years after exposure. Macrophages in lung lavage fluid (LLF) were increased at 16, 24 and 93 weeks and lymphocytes at 24 weeks. Examination of lung wall cells (LWC) 2 years after exposure compared to cells obtained by LLF showed higher proportions of LWC lymphocytes and neutrophils. Percoll gradient centrifugation of these cells showed a higher proportion of high density macrophages in LLF from the amosite-exposed animal and an increased number of low density lymphocytes in the LW. Cathepsin D was increased in LLF at 8 and 24 weeks and in alveolar macrophages 24 weeks and 2 years after exposure. Fibroblast cultures exposed to LLF did not show any statistical significant changes in their collagen synthesis. Histology 93 weeks after exposure showed macrophage and mediastinal lymph node accumulation of asbestos, as well as collagen in alveolar walls. Granulomas were found in the vicinity of blood vessels and in connection with the bronchioles. The data suggest that amosite at low doses ultimately causes fibrosis with a reaction pattern different from that seen in silicosis. The inflammation and fibrosis seems to develop only within the interstitium.

In plain English

In this animal experiment in Gothenburg, Sweden, 46 guinea pigs breathed UICC standard amosite asbestos dust through their noses, 2 hours a day, 5 days a week: 30 for 3 weeks averaging 49 mg/m3 and 16 for 6 weeks at 47 mg/m3. They were compared with unexposed controls up to 93 weeks, some at 2 years, after exposure ended. The authors estimated the lung dose at about 2.1 mg (3 weeks) or 4.2 mg (6 weeks), which they called low compared with windpipe-injection experiments giving 20-30 mg. Macrophages and lymphocytes washed from the lungs were significantly increased in number only at 24 weeks. After the 6-week exposure, Cathepsin D, an enzyme, rose in lung washings at 8 and 24 weeks and inside lung cells at 24 and 93 weeks. Lung washings did not significantly change collagen production by cultured lung cells. At 93 weeks after the 6-week exposure, the lungs showed scars, granulomas and collagen in the alveolar walls. The authors concluded that the results suggest amosite causes fibrosis in guinea pigs at low doses, with a long latency period.

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: guinea pigs were exposed nose-only and compared with unexposed control animals. The study used lung washing (lavage), lung wall cell preparation, enzyme measurements, fibroblast cell cultures and histology.
• Who was studied: 46 guinea pigs (300-400 g) were exposed to amosite, alongside control animals from the same batch, at the Department of Environmental Hygiene, University of Gothenburg, Sweden. Animals were examined at 4, 8, 16, 24, 50 and 93 weeks after exposure, with at least 4 guinea pigs per group and time point. Five exposed animals and 5 controls were killed 2 years after exposure.
• Exposure: UICC standard amosite dust, 2 h/day, 5 days/week. The methods give an overall average concentration of 49 mg/m3. The results give separate group averages: 30 animals for 3 weeks at 49 mg/m3 and 16 animals for 6 weeks at 47 mg/m3.
• Main results:
  • The authors calculated the lung burden as about 2.1 mg amosite per lung for the 3-week exposure and 4.2 mg per lung for the 6-week exposure. They called this a low dose compared with intratracheal injection experiments, in which 20-30 mg may be given.
  • No outward signs of disease due to exposure were seen in the animals, and the lungs looked normal.
  • Alveolar macrophages in lung lavage fluid were significantly increased only at 24 weeks after exposure: 9.9 x 10^6 in controls vs 17.5 (3-week group) and 16.0 (6-week group), P less than 0.01 and 0.001 respectively.
  • Lymphocytes in lung lavage fluid were also significantly increased at 24 weeks: 1.5 x 10^6 in controls vs 3.5 and 5.5, P less than 0.01 and 0.001 respectively. No increase in neutrophils was found.
  • At 2 years, high-density macrophages in lung lavage fluid were increased in exposed animals (6% vs 18%, P less than 0.01). These macrophages were heavily loaded with small amosite fibers.
  • At 2 years, low-density lymphocytes among lung wall cells were significantly increased after amosite exposure (12% vs 21%).
  • After the 6-week exposure, N-acetyl-beta-D-glucosaminidase and Cathepsin D activity in lung lavage fluid were increased at 8 and 24 weeks. The discussion states that only Cathepsin D was significantly increased at 24 weeks. All enzyme activities were at control values at 93 weeks, and there was no increase of LDH.
  • In free lung cells from lavage, Cathepsin D was significantly increased at 24 and 93 weeks after the 6-week exposure, and acid phosphatase was also increased at 93 weeks. There was no difference after the 3-week exposure.
  • Cultured lung fibroblasts were given lavage fluid from 6-week-exposed animals. Their collagen synthesis was increased by 40% at 8 weeks and decreased by 50% at 93 weeks, and neither change was statistically significant. At 24 weeks, protein synthesis was almost twice the control level (P less than 0.05, while the authors' stated significance level was P less than 0.01).
  • No lesions were found up to 50 weeks after the 3-week exposure, although there were more macrophages in the alveoli and the alveolar walls were thickened.
  • At 93 weeks after the 6-week exposure, the lungs showed dark scars and dots on the surface. They also showed granulomas near the bronchioles and near blood vessels with asbestos fibers, and alveolar walls thickened with collagen fibers. Mediastinal lymph nodes contained aggregates of asbestos particles.
• The authors' conclusion: The authors concluded that the results of these guinea pig experiments suggest amosite causes fibrosis at low doses but with a long latency period. They described its main features as an early increase in lung wall lymphocytes and airway macrophages and a persistent increase in macrophage production of Cathepsin D. They reported that the histological changes were different from those caused by inhaled silica.
• Limitations the authors state:
  • The size of the asbestos fibers was not measured. The authors relied on other authors' measurements of UICC standard amosite.
  • Different kinds of macrophages were not identified. The authors assumed that less than 20% of lung wall cells came from the free lung cell population.

Topics

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

Medical terms in this study, explained in our Lexicon: Amosite, Macrophage, Alveolar Macrophage, Fibroblast, Collagen, Histology, Granuloma, Fibrosis.

Related studies

• Asbestos-body formation in the lungs of rats and guinea-pigs after inhalation of anthophyllite — S.K. Botham, P.F. Holt (1972)
• Biochemical changes and pulmonary response of guinea pigs to asbestos dust — J. Singh, M.U. Beg, et al. (1976)
• The development of glass-fibre bodies in the lungs of guinea-pigs — S.K. Botham, P.F. Holt (1971)
• Failure of macrophage activation to induce pulmonary fibrosis in asbestos-exposed guinea-pigs — R.J. Emerson, P.J. Cole (1983)
• The effects of inhaled crocidolites from Transvaal and North-west Cape mines on the lungs of rats and guinea-pigs — S.K. Botham, P.F. Holt (1972)
• Rapid short-term clearance of chrysotile compared with amosite asbestos in the guinea pig — A. Churg, J.L. Wright, et al. (1989)

Browse more research in Toxicology, or return to medical research.