Mast cells and inhalation of asbestos in rats

Our plain-English summary of Mast cells and inhalation of asbestos in rats, by M.M. Wagner, R.E. Edwards, C.B. Moncrieff, et al (Thorax, 1984).

The study

• Authors: M.M. Wagner, R.E. Edwards, C.B. Moncrieff, J.C. Wagner
• Journal: Thorax
• Published: 1984;39(7):539-44
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mast cell counts were performed on sections taken from the lungs of rats exposed by inhalation to different UICC samples of asbestos fibres for periods ranging from a few days to two years. A comparison of mast cell counts with grades of fibrosis showed that there is a sevenfold increase when there is interlobular linking of the fibrotic lesions (grade 5). Submesothelial mast cells showed a trend of increasing numbers with increasing exposure and with increasing subpleural thickening. Each type of asbestos produced a steady increase in mast cell numbers with increasing exposure. Two samples from animals exposed to chrysotile and two from animals exposed to amphiboles (crocidolite and amosite respectively) had 10 times as many cells as the control group after six and 24 months' exposure. Another amphibole, anthophyllite, produced 50 times more cells than were present in the control specimen appropriate for the heaviest exposure. These results are briefly discussed in relation to further exposure, smoking, and characteristics of the dusts.

In plain English

This was a retrospective animal study from the Medical Research Council Pneumoconiosis Unit in Penarth. The authors counted mast cells, cells involved in inflammation, in preserved lung sections from control rats and from Wistar rats that had breathed one of five standard asbestos samples. These were amosite, crocidolite, anthophyllite and two chrysotiles, given for two to three days up to 24 months. Mast cells rose steadily with the severity of lung fibrosis. In the lung interior there was at least a 100-fold increase from grade 1 (normal lung) to grades 5 to 8, with a sevenfold rise between grades 4 and 5. Each asbestos type produced a considerable rise with longer exposure. Anthophyllite stood apart: after 24 months, the 4 exposed rats had an estimated geometric mean of 2846 mast cells per average lung section of 3.14 square centimetres, against 132 in 5 controls. The authors concluded that mast cells are associated with asbestos-induced interstitial fibrosis in rats. They said formal statistical testing was limited because material from many of the original rats could not be analysed.

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: Retrospective animal study using lung sections from rats previously exposed to asbestos by inhalation
• Who was studied: Specific pathogen free Wistar rats exposed in inhalation chambers, plus a group of unexposed control rats, at the Medical Research Council Pneumoconiosis Unit, Llandough Hospital, Penarth. Exposure groups were small: 1 to 7 rats per dust and time point. Rats found dead or killed because of illness were not included.
• Exposure: Five UICC standard reference asbestos samples: amosite, crocidolite, anthophyllite, chrysotile A (Rhodesian) and chrysotile B (Canadian). Dust clouds were given 7 hours a day, 5 days a week. Exposure lasted 2 to 3 days, 2 months, 3 months, 6 months (rats then killed after a further 18 months) or 24 months. Dust concentrations are not given in this article.
• Main results:
  • The counts in the tables are estimated group (geometric) means, converted to apply to an average lung section of 3.14 square centimetres in area and 3.26 mm in pleural length. They are not whole-lung counts or totals across rats.
  • Total lung mast cells increased steadily with the grade of lung fibrosis. There was a 20-fold increase between grade 1 and grades 6 to 7.
  • In the lung interior there was at least a 100-fold increase from grade 1 to grades 5 to 8, with a sevenfold increase between grades 4 and 5. The share of mast cells in the lung interior was 38% at grade 4 and 84% at grade 5.
  • Subpleural mast cells increased steadily with the grade of subpleural thickening. The mean count per average section of 3.26 mm pleural length rose from 39 in grade A (39 rats) to 323 in grade D (4 rats). Of the 4 grade D rats, 3 had been exposed to anthophyllite and 1 to chrysotile A, all for 24 months.
  • The authors found no consistent difference between the two chrysotile samples, or between amosite and crocidolite. Anthophyllite was completely different.
  • Mast cell numbers in the total lung rose considerably with increasing exposure to each dust. Only one rat was exposed to amosite for six months.
  • Up to three months there was little difference between exposed and unexposed rats, because mast cell numbers also rose with age.
  • After 24 months of exposure, the estimated geometric mean total lung count per average section of 3.14 square centimetres was 2846 in 4 anthophyllite-exposed rats. The corresponding figure was 132 in 5 control rats.
  • In the lung interior at three months, rats exposed to anthophyllite and to the two chrysotiles had five times more mast cells than control rats and than rats exposed to amosite or crocidolite.
  • Among rats killed at 24 months, lung interior counts were slightly higher in rats exposed to amosite or crocidolite for only six months than in rats exposed for the full period. For the two chrysotile dusts the reverse was true.
  • In the subpleural region, amosite and crocidolite gave a small, steady rise from two months onwards that was greater than the rise with the chrysotile dusts. Anthophyllite produced no rise with less than six months' exposure.
  • In exposed rats, the extra mast cells were found within the interstitial fibrous lesions, with some in nearby alveoli.
• The authors' conclusion: The authors concluded that mast cells are associated with the interstitial fibrosis caused by asbestos fibres in rats. They placed the greatest increase at the transition from minimal asbestosis to asbestosis that would be clinically apparent. In discussion they suggested, without testing it in this study, that further exposure or smoking could trigger mast cell mediator release in people with moderate asbestosis.
• Limitations the authors state:
  • Formal statistical testing was limited. Material could not be analysed from a large proportion of the original rats, because they had died before their term or had already been used to measure dust.
  • There were too few rats for the authors to comment on the higher count at grade 6 than at grade 7, or on the very high count at grade 8.
  • The authors said formal significance tests would be inappropriate for comparing the size of increases between fibrosis grades.

Topics

Medical terms in this study, explained in our Lexicon: UICC, Fibrosis, Chrysotile, Amphibole Group, Crocidolite, Amosite, Anthophyllite.

Related studies

• Asbestos-induced fibrosis in rats: increase in lung mast cells and autacoid contents — I. Keith, R. Day, et al. (1987)
• Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2016)
• Different hormonal responses of mast cells in gastric mucosa and dermis in the rat — T. Räsänen (1967)
• Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats — S.H. Gavett, C.U. Parkinson, et al. (2016)
• Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz — J.M. Davis, A.D. Jones, et al. (1991)
• Accumulation of mixed mineral dusts in the lungs of rats during chronic inhalation exposure — C.H. McMillan, A.D. Jones, et al. (1989)

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