Asbestos-induced fibrosis in rats: increase in lung mast cells and autacoid contents

Our plain-English summary of Asbestos-induced fibrosis in rats: increase in lung mast cells and autacoid contents, by I. Keith, R. Day, S. Lemaire, et al (Experimental Lung Research, 1987).

The study

• Authors: I. Keith, R. Day, S. Lemaire, I. Lemaire
• Journal: Experimental Lung Research
• Published: 1987;13(3):311-27
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Adult male Wistar rats were treated with one tracheal instillation of 5 or 10 mg chrysotile B asbestos fibers in 0.5 ml saline, or 0.5 ml saline only (controls). Rats were killed at 1, 3, and 6 months postinstillation. Serotonin and histamine were quantitated in lung tissue homogenate using high-performance liquid chromatography with electrochemical and fluorometric detection, respectively. Serotonin was also quantitated in the cytoplasm of grouped (NEB) and individual (NEC) neuroendocrine cells and in mast cells using formaldehyde vapor-induced fluorescence and microspectrofluorometry, and density indices of NEBs, NECs, and mast cells were determined. Tissue edema, fibrotic lesions, and medial hypertrophy of pulmonary arterioles were assessed morphometrically. Test rats had higher pulmonary serotonin and histamine levels than controls at 1, 3, and 6 months. They also had higher cellular serotonin in NEBs at 1 month, but not in NECs, and tended to have higher serotonin levels in mast cells at 6 months. Mast cell numbers were higher among tests at 1 and 3 months, whereas NEBs and NECs were unchanged by asbestos. There was no difference between tests and controls in the amount of tissue edema at any time. However, all test rats had distinct lung lesions characterized by peribronchiolar fibrosis and bronchiolitis obliterans. No such lesions were present among control rats. Typically, mast cells were located immediately beneath the epithelial basal lamina of the bronchiolar fibrotic projections and at their stalks, whereas no mast cells were noted beneath normal epithelium, indicating a role of mast cells in asbestos-induced peribronchiolar fibrosis. Moreover, arteriolar medial hypertrophy at all three ages in conjunction with the increased levels of serotonin was an index of putative chronic pulmonary hypertension. Our results suggest that asbestos-induced rises in serotonin and histamine are due primarily to increased numbers of mast cells.

In plain English

This was an animal experiment. Adult male Wistar rats received a single instillation into the windpipe of either saline alone (27 control rats) or UICC Canadian chrysotile B asbestos at 5 mg (33 rats) or 10 mg (16 rats). The rats were killed 1, 3 or 6 months later. One month after exposure, lung serotonin was 1.8-fold higher in the 5 mg group and 2.9-fold higher in the 10 mg group, and the increase persisted at 3 and 6 months. In the 5 mg group, lung histamine rose 2-, 1.8- and 1.4-fold at 1, 3 and 6 months. Mast cell density was significantly higher in treated rats at 1 and 3 months but not at 6 months. All treated rats, unlike controls, developed peribronchiolar fibrosis with bronchiolitis obliterans, seen in 33-45% of bronchioles, and mast cells lay beneath these lesions. The muscular wall of small lung arteries was thicker at 3 and 6 months. No signs of cancer were found. The authors concluded that the rise in serotonin and histamine probably came mainly from the increased number of mast 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 experiment: single intratracheal instillation of asbestos or saline in rats, with lungs examined at 1, 3 and 6 months
• Who was studied: Adult male Wistar rats: 27 saline controls, 33 given 5 mg asbestos and 16 given 10 mg asbestos. Many measurements used six rats per group.
• Exposure: One intratracheal instillation of 5 mg or 10 mg UICC Canadian chrysotile B asbestos in 0.5 ml saline. Controls received 0.5 ml saline only.
• Main results:
  • One month after exposure, lung serotonin was increased 1.8-fold in the 5 mg group and 2.9-fold in the 10 mg group compared with controls. The significant increase persisted at 3 and 6 months.
  • In the 5 mg group, lung histamine showed a significant and persistent increase: 2-fold at 1 month, 1.8-fold at 3 months and 1.4-fold at 6 months.
  • Serotonin inside clustered neuroendocrine cells (NEBs) was higher in treated rats at 1 month only. Serotonin in single neuroendocrine cells (NECs) did not differ at any time. Mast cell serotonin tended to increase in treated rats at 6 months (p = 0.1).
  • Mast cell density index in treated versus control rats: 610.81 vs 246.79 at 1 month (p less than 0.05); 659.55 vs 382.50 at 3 months (p less than 0.01); 693.35 vs 546.47 at 6 months (not significant). Density of NEBs and NECs did not differ at any time.
  • Alveolar and interstitial edema was not noticeable at 1, 3 or 6 months after treatment.
  • In contrast to controls, all treated rats developed peribronchiolar fibrosis and papillomatous projections of the airway lining (bronchiolitis obliterans). These lesions were present in 33-45% of bronchioles and occupied about 50% of the lumen in affected airways.
  • Mast cells were typically located beneath the lining of the bronchiolar papillomatous projections.
  • In treated rats, the medial thickness index of pulmonary arterioles was significantly raised at 3 and 6 months, and the arteriolar surface index was increased at 1, 3 and 6 months.
  • No evidence of neoplasia was found. Enlarged NEBs were seen in one rat 6 months after 5 mg asbestos.
• The authors' conclusion: The authors concluded that asbestos-induced lung injury was associated with increased lung serotonin and histamine, and that this rise originated mainly from mast cells, probably because there were more of them. Their results did not exclude increased content per cell as well. They also concluded that the position of mast cells in the papillomatous projections suggested a link to the fibrotic response.
• Limitations the authors state:
  • The authors stated that the significance of the raised serotonin levels was not clear. Their suggestion that serotonin contributed to pulmonary hypertension was offered as speculation.
  • The authors stated that it was not known whether the extra mast cells came from replication of existing mast cells, migration from other sites, or differentiation from precursors, and that this needs further study.
  • The authors stated that their results did not exclude a possible increase in amine content per cell as well.
  • The authors noted that NEB and NEC density indices were generally higher than expected in adult rats, possibly because of variation between batches of rats.

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Chrysotile, Epithelium, Pulmonary Hypertension.

Related studies

• Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis — R. Day, S. Lemaire, et al. (1987)
• Mast cells and inhalation of asbestos in rats — M.M. Wagner, R.E. Edwards, et al. (1984)
• 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)
• Upregulation of the PDGF-alpha receptor precedes asbestos-induced lung fibrosis in rats — J.A. Lasky, B. Tonthat, et al. (1998)
• Different hormonal responses of mast cells in gastric mucosa and dermis in the rat — T. Räsänen (1967)
• Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats — T.D. Perdue, A.R. Brody (1994)

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