In vitro models of lung toxicity

Our plain-English summary of In vitro models of lung toxicity, by G.L. Fisher, M.E. Placke (Toxicology, 1987).

The study

• Authors: G.L. Fisher, M.E. Placke
• Journal: Toxicology
• Published: 1987;47(1-2):71-93
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In vitro assays that emphasize cellular components critical to the host defense system have been developed to evaluate pulmonary toxicity and define deleterious changes in parenchymal cell populations. Assays that employ pulmonary alveolar macrophages (PAM) have demonstrated good correlation between macrophage toxicity and pulmonary fibrogenicity for many inorganic compounds. The PAM assays provide simple and inexpensive screens of potential respiratory tract toxicity. Many investigators screen chemicals for their ability to alter the mucosal epithelial cell conducting airways by performing tracheal organ cultures. The tracheal assays have also provided useful screens for Vitamin A analogues required for epithelial cell differentiation. Most recently, in vitro respiratory tract models have been extended to include whole-lung explants, an approach that allows for development of fibrosis and epithelial cell toxicity after in vitro exposure to inorganic and organic fibrogens. The whole-lung explant system appears to duplicate the in vivo response to a variety of lung toxins, including bleomycin, silica, and crocidolite asbestos. Together, these assays provide a description of potential toxicity to key components of the lung, emphasizing the pulmonary macrophage, conducting airways, and alveolar septae. It is expected that continued research in these models will enhance their predictive abilities and utility in risk assessment.

In plain English

This article was the authors' review of laboratory (in vitro) methods for testing lung toxicity, drawn mainly from their own earlier studies. It covered three systems: scavenger cells (macrophages) washed from cattle lungs, small pieces of hamster windpipe (trachea), and thin slices of whole lung kept alive in culture. In lung slices, crocidolite asbestos caused interstitial fibrosis (scarring of lung tissue) on a time frame similar to silica. The scarring was multifocal to regional, and the asbestos also caused squamous metaplasia (a change in lining cells) in the small airways. Glass beads, used as an inert comparison, caused no significant lesions. In windpipe cultures, tissue from younger hamsters was more sensitive to asbestos or benzo(a)pyrene. A collaborative study of heated and irradiated chrysotile gave results the authors described as consistent with chrysotile toxicity working through electron transfer. The authors noted that the lung cultures lacked the surrounding inflammatory response seen in whole animals. They concluded that the lung-slice system appeared to mimic whole-animal responses to scar-causing substances. The article gave no asbestos doses.

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: Review of in vitro (cell and organ culture) lung toxicity models, describing mainly the authors' own laboratory studies
• Who was studied: Animal cells and tissues, not people: alveolar macrophages from a healthy adult steer at slaughter; tracheal and whole-lung explants from female golden Syrian hamsters; peripheral lung cultures also from rat, human and bovine tissue. Numbers of animals are not given.
• Exposure: Crocidolite asbestos (lung explants); heated and irradiated chrysotile asbestos (macrophage and other assays); asbestos of unstated type (tracheal age study). Other agents included silica, paraquat, bleomycin, benzo(a)pyrene, nickel compounds, trace elements and fly ash. Glass beads served as an inert control. Asbestos doses are not reported.
• Main results:
  • In lung explants, each of silica, asbestos, paraquat and bleomycin caused progressive interstitial fibrosis over four weeks after exposure
  • In lung explants exposed to crocidolite, the fibrosis was multifocal to regional, and squamous metaplasia developed in the airway lining along respiratory bronchioles and alveolar ducts
  • Lung explants exposed to 5 mg/ml of glass beads (inert control) showed no significant lesions
  • Lung explants differed from whole animals in that no surrounding inflammatory response developed
  • Tracheal tissue from 30-, 100- and 180-day-old hamsters showed age-dependent sensitivity to asbestos or benzo(a)pyrene. The most severe changes were in tissue from 30-day-old animals compared with 100-day-old animals.
  • In a collaborative study of heated and irradiated chrysotile, all assays gave similar responses, which the authors described as consistent with chrysotile toxicity being mediated through electron transfer
• The authors' conclusion: The authors concluded that the lung explant system's response to a variety of fibrogens appeared to mimic whole-animal responses, and that these in vitro assays can be used to screen lung toxicants and to complement standard animal testing

Topics

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

Related studies

• A possible mechanism of chrysotile asbestos toxicity — G.L. Fisher, B.T. Mossman, et al. (1987)
• A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials — V.C. Sanchez, P. Weston, et al. (2011)
• Asbestos in peripheral lung culture a species comparison of pulmonary tissue response — M.E. Placke, G.L. Fisher (1987)
• Assessment of the pathogenic potential of asbestiform vs. nonasbestiform particulates (cleavage fragments) in in vitro (cell or organ culture) models and bioassays — B.T. Mossman (2008)
• Pulmonary toxicity of wollastonite in vivo and in vitro — E. Tátrai, Z. Kováciková, et al. (2004)
• Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation — H. Barosova, S. Chortarea, et al. (2018)

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