Asbestos in peripheral lung culture a species comparison of pulmonary tissue response

Our plain-English summary of Asbestos in peripheral lung culture a species comparison of pulmonary tissue response, by M.E. Placke, G.L. Fisher (Drug and Chemical Toxicology, 1987).

The study

• Authors: M.E. Placke, G.L. Fisher
• Journal: Drug and Chemical Toxicology
• Published: 1987;10(1-2):133-56
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We have recently developed culture techniques to allow the long-term maintenance of adult peripheral lung tissue in vitro from a variety of mammalian species including hamster, rat, bovine, and human. The technique involves perfusion of the major airways with agarose gel and culture media followed by thin sectioning and culture on porous surgical foam. Cross sections of lung lobes 1-2 mm thick have been cultured for periods beyond four weeks with maintenance of structural and biochemical integrity of the lung. In vitro exposure of lung explants to crocidolite asbestos through the airways produced fibrotic and hyperplastic lesions similar to those reported after in vivo exposure. The incidence and severity of interstitial fibrous was concentration-dependent, including the human specimens, and the morphologic appearance of the lesions was similar in explants derived from each species. The lung explant model is well suited for further mechanistic evaluations of asbestos-induced lung lesions. It is notable that the pulmonary lesions were produced without the possibility for recruitment of hematogenous inflammatory cell populations.

In plain English

This was a laboratory study. The authors kept thin slices of adult lung alive in culture from hamsters, rats, cattle and humans. The human tissue was uninvolved lung removed during lung cancer surgery. They introduced crocidolite asbestos into the airways at 5, 50, 500 or 5000 micrograms per millilitre; human tissue received only 500 and 5000. Comparison slices received glass beads or no treatment, and tissue was examined under the microscope for up to four weeks. Glass beads caused few differences from untreated tissue. In asbestos-exposed slices, cell damage appeared in the first two weeks, and moderate-to-marked interstitial fibrosis was present by four weeks. Lesions looked similar across the four species. Severity rose with concentration from 5 through 500, while 5000 caused widespread cell death that limited fibrosis. Hamster tissue seemed least sensitive. The authors reported that changes in human tissue were more severe than in the other species, including squamous foci resembling early squamous cell carcinomas. The authors concluded that inflammation recruited from the blood may simply modulate or worsen the lung tissue damage.

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: Laboratory (in vitro) experiment using cultured slices of lung tissue (lung explants) exposed to asbestos
• Who was studied: Lung tissue from 5- to 6-week-old female golden Syrian hamsters and Fischer 344 rats (about 12-15 animals used), from freshly slaughtered steers, and from human lung cancer surgery patients (uninvolved lung; long-term smokers with bronchiogenic adenocarcinoma). Only one bovine or human subject was needed per concentration. The article reports 6-9 lung explants examined at each time point.
• Exposure: Crocidolite asbestos suspended in the agarose infusion at 5000, 500, 50 and 5 micrograms per millilitre (human lung only 5000 and 500). Controls were 500 micrograms per millilitre glass beads, and untreated cultures. Tissue was collected at explantation and at 7, 14 and 28 days.
• Main results:
  • Explants from each species exposed to glass beads showed few differences from untreated controls, apart from a minimal increase in free alveolar macrophages.
  • The appearance and sequence of tissue changes after asbestos were similar in lung from all four species.
  • Asbestos-exposed explants collected after four weeks had moderate-to-marked interstitial fibrosis, following degenerative and cytotoxic changes in the first two weeks.
  • Lesion severity increased with asbestos concentration from 5 through 500 micrograms per millilitre. At 5000, extensive degeneration and necrosis meant fibrosis was less widespread than in lower-dose tissue.
  • Hamster explants seemed least sensitive. Rat and human tissue showed more collagen staining than bovine or hamster tissue, and bovine tissue showed more cellular proliferation.
  • In human lung tissue, which already had mild to moderate emphysema and minimal to mild fibrosis, the authors reported that asbestos increased interstitial fibrosis and caused metaplastic and hyperplastic changes more severe than in the other species.
  • Asbestos caused squamous metaplasia and dysplasia in airways. In human lung explants exposed to 500 micrograms per millilitre, squamous foci resembled early squamous cell carcinomas.
  • Unlike in whole animals, the explants showed no inflammatory infiltrate (granulomatous response) in the distal lung.
• The authors' conclusion: The authors concluded that because fibrosis developed without systemic influences, inflammation including recruitment of cells from the circulation may simply modulate or exacerbate the primary lung tissue damage. They also concluded that the explant model is well suited for further study of how asbestos causes lung lesions.
• Limitations the authors state:
  • Human lung was tested at only two concentrations because little tissue was available.
  • In a few bovine and human cases, regional differences in lesions were due to uneven distribution of asbestos during instillation.

Topics

Medical terms in this study, explained in our Lexicon: Crocidolite, Interstitial.

Related studies

• Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers — D.B. Warheit, S.I. Snajdr, et al. (1997)
• In vitro models of lung toxicity — G.L. Fisher, M.E. Placke (1987)
• Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene — V.J. Feron, P.M. Scherrenberg, et al. (1985)
• Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase — M. Dörger, A.M. Allmeling, et al. (2002)
• A novel system for the culture of human lung: lung development and the response to injury — M.T. Hsu, M. Dimaio, et al. (1992)
• Interaction of asbestos with metaplastic squamous epithelium developing in organ cultures of hamster trachea — C.D. Woodworth, B.T. Mossman, et al. (1983)

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