Chrysotile-induced asbestosis: changes in the free cell population, pulmonary surfactant and whole lung tissue of rats

Our plain-English summary of Chrysotile-induced asbestosis: changes in the free cell population, pulmonary surfactant and whole lung tissue of rats, by T.D. Tetley, P.M. Hext, R.J. Richards, et al (British Journal of Experimental Pathology, 1976).

The study

• Authors: T.D. Tetley, P.M. Hext, R.J. Richards, M. McDermott
• Journal: British Journal of Experimental Pathology
• Published: 1976;57(5):505-14
• Cited by: 71 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Rats inhaling chrysotile asbestos contracted asbestosis and fibrosis of the lungs. Studies of biochemical and morphological changes (between normal and treated animals) show that chrysotile induces an increase in the lung free cell population and pulmonary surfactant levels. Lysosomal enzyme levels are elevated in both the whole lung and free cell population and there are considerable changes in macrophage morphology. It is suggested that the primary response of the lung to chrysotile is an increase in surfactant production coupled with an increase in free cell numbers, in order to prevent the cytotoxic effect of the dust.

In plain English

This was an animal experiment. The authors exposed specific pathogen-free rats to UICC Rhodesian chrysotile asbestos in inhalation chambers for 7 hours a day, 5 days a week, for 15 weeks. They compared them with an unexposed control group matched by age and sex. Rats were killed 7, 15, 30 and 50 weeks after first exposure. The article does not say how many rats were used. No rats developed lung tumours during the study. Grade 3 asbestosis was found in some exposed rats at 15 weeks and consistently at 30 and 50 weeks. At 15 weeks, exposed rats had about three times as many free lung cells (mostly macrophages) as controls, and ten times as much pulmonary surfactant. By 30 weeks, free cell numbers were similar to controls, while surfactant was still twice as high. Macrophages in exposed rats were larger and often had two or more nuclei. Lysosomal enzyme activity in whole lung was mostly higher. The authors concluded that surfactant and macrophage changes appeared to be a primary response to inhaled chrysotile, but that their significance for asbestosis was unclear.

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 experiment (inhalation study in rats); the authors call it preliminary studies
• Who was studied: Specific pathogen-free rats, divided into two equivalent groups by age and sex: one unexposed control group and one exposed group. Exposure took place at the M.R.C. Pneumoconiosis Unit, Llandough Hospital, South Wales. Rats were killed 7, 15, 30 and 50 weeks after the first day of exposure. The total number of rats is not stated.
• Exposure: Inhaled UICC Rhodesian chrysotile asbestos in inhalation chambers, 7 hours a day, 5 days a week, for 15 weeks in total. The concentration is printed as '12-5 mg/m3' (probably 12.5 mg/m3; OCR-damaged). Rats killed at 30 and 50 weeks had 15 and 35 weeks without dust.
• Main results:
  • No animals developed lung tumours during the study. Grade 3 asbestosis was found in some exposed rats at 15 weeks and was consistently apparent in exposed rats at 30 and 50 weeks.
  • In exposed rats, the number of free lung cells rose by 7 weeks and showed a three-fold increase by 15 weeks. The table gives a mean of 42.8 x 10^6 cells per animal in exposed rats versus 15.5 x 10^6 in controls.
  • At 30 weeks there was no difference in free cell numbers between exposed and control rats. At 50 weeks the mean was higher in exposed rats, but several exposed rats were not significantly different from controls.
  • Exposed rats had higher lung weights than control rats.
  • In both groups, 98% or more of free cells looked like macrophages. In exposed rats the cells were larger, most markedly at 7 and 15 weeks, when 50% or more were larger than in controls.
  • Cells with two or more nuclei were common among free cells of exposed rats. Control lungs had no multinucleate free cells.
  • Lysosomal enzyme activities in whole lungs of exposed rats were much higher than in controls at all time points, with two exceptions: acid phosphatase at 30 weeks and acid ribonuclease at 7 weeks.
  • At 15 weeks, lipase activity in the lungs of exposed rats was 8 times that in controls.
  • In general, the free (macrophage) cells contributed a relatively small share (6%) of total lung enzyme activity in both groups. The exceptions were lipase and cathepsin D, which accounted for 9-60% and 2-32% of the total lung levels respectively.
  • Pulmonary surfactant showed a ten-fold increase per animal in exposed rats after 15 weeks of exposure.
  • At 30 weeks (after 15 weeks without dust), surfactant in exposed rats was twice as high as in controls.
  • At 50 weeks, the material isolated as surfactant in exposed rats was up to 5 times that in controls. Some of these 50-week samples were contaminated with cell membrane fragments.
• The authors' conclusion: The authors concluded that surfactant production appeared to be increased in chrysotile-exposed rats as an additional protective mechanism alongside the free cells. They suggested that surfactant build-up combined with macrophage changes is a primary response to inhaled chrysotile.
• Limitations the authors state:
  • No enzyme levels were recorded for the 50-week free cell sample because the material was lost.
  • Surfactant isolated from some exposed rats at 50 weeks was contaminated with cell membrane fragments.
  • The study could not show whether chrysotile causes selective release of lysosomal enzymes from macrophages in the living animal.
  • The authors stated that the significance of the findings for asbestosis was unclear and gave no direct link to involvement of interstitial tissue in pulmonary fibrosis.

Topics

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

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

Related studies

• Changes in pulmonary surfactant and phosphatidylcholine metabolism in rats exposed to chrysotile asbestos dust — T.D. Tetley, R.J. Richards, et al. (1977)
• Studies on the fate of pulmonary surfactant in the lung — R. Desai, T.D. Tetley, et al. (1978)
• Changes in surfactant in bronchoalveolar lavage fluid after hemithorax irradiation in patients with mesothelioma — M. Hallman, P. Maasilta, et al. (1990)
• Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis — R. Day, S. Lemaire, et al. (1987)
• Pulmonary bombesin in experimentally induced asbestosis in rats — R. Day, I. Lemaire, et al. (1985)
• Effect of air pollutants on the pulmonary surfactant system — B. Müller, C. Seifart, et al. (1998)

Browse more research in British Journal of Experimental Pathology, or return to medical research.