Development and characterization of a rapid-onset rodent inhalation model of asbestosis for disease prevention

Our plain-English summary of Development and characterization of a rapid-onset rodent inhalation model of asbestosis for disease prevention, by B.T. Mossman, Y.M. Janssen, J.P. Marsh, et al (Toxicologic Pathology, 1991).

The study

• Authors: B.T. Mossman, Y.M. Janssen, J.P. Marsh, A. Sesko, M.A. Shatos, J. Doherty, K.B. Adler, D. Hemenway, R. Mickey, Vacek
• Journal: Toxicologic Pathology
• Published: 1991;19(4 Pt 1):412-8
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A short-term inhalation model of asbestosis was developed in rodents to examine possible preventive approaches to lung disease. Fischer 344 (F344) rats were exposed for 10 and 20 days to National Institute of Environmental Health Sciences (NIEHS) crocidolite asbestos while sham controls were exposed to air only. To determine quantitative biochemical indicators of asbestos-induced lung disease, bronchoalveolar lavage (BAL) fluids were analyzed for lactic dehydrogenase (LDH), alkaline phosphatase, angiotensin-converting enzyme (ACE), and protein. Total and differential cell counts were performed on cell pellets from BAL. Lungs from additional rats were processed for histopathology, measurement of hydroxyproline, and autoradiography after injection of rats with 3H-thymidine. Exposure to asbestos for 10 and 20 days caused increases in LDH, alkaline phosphatase, and protein in BAL. In contrast, ACE was undetectable in BAL fluids from sham or asbestos-exposed rats. At both time periods, the percentages of polymorphonuclear leukocytes (PMNs) and lymphocytes in BAL were increased in asbestos-exposed rats. Total cell numbers in BAL were increased significantly at 20 days in animals inhaling asbestos. Exposure to asbestos for 10 and 20 days caused elevated amounts of hydroxyproline in lung and the development of fibrotic lesions. Asbestos-exposed rats exhibited increased numbers of interstitial cells and airspace epithelial cells incorporating 3H-thymidine, whereas labeled bronchiolar epithelial cells were not elevated significantly. The quantitative changes in asbestos-associated enzyme levels, cell types and protein in BAL, as well as increases in hydroxyproline and morphologic evidence of fibrosis, are useful indices of asbestos-related lung injury which enable preventive and therapeutic approaches to disease.

In plain English

This animal inhalation experiment developed a short-term rat model of asbestosis. Male Fischer 344 rats (4 per group per time point, in duplicate or triplicate experiments) inhaled NIEHS crocidolite asbestos at a time-weighted average of 7-10 mg/m3, 6 hours a day, 5 days a week, for 10 and 20 days; sham rats were placed in chambers without asbestos. Bronchoalveolar lavage (BAL) fluid, lung hydroxyproline, histopathology graded for fibrosis, and 3H-thymidine labelling were measured. In asbestos-exposed rats, lactic dehydrogenase, alkaline phosphatase and protein in BAL were increased at both 10 and 20 days, while angiotensin-converting enzyme was not detected in either group. In control rats over 98% of BAL cells were alveolar macrophages, whereas in exposed rats polymorphonuclear leukocytes made up about 15-22% and lymphocytes 5-8%. Lung hydroxyproline was elevated at 10 and 20 days, more so at 20 days. Focal fibrotic lesions appeared at 10 days, but the fibrosis grade was significantly elevated only at 20 days. The authors concluded that biochemically detecting collagen synthesis appeared more sensitive than histology for measuring incipient fibrotic changes.

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 inhalation experiment developing a short-term (rapid-onset) rat model of asbestosis, with sham-exposed controls
• Who was studied: Male Fischer 344 rats weighing 200-250 g, 4 rats per group per time point, each experiment done in duplicate or triplicate; laboratory study (University of Vermont and Georgetown University)
• Exposure: Inhaled NIEHS crocidolite asbestos, 7-10 mg/m3 air, 6 hours/day, 5 days/week, for 10 and 20 days; sham rats in chambers without asbestos; fibers 3-50 micrometres long, average about 11.5 micrometres, average aspect ratio about 14:1
• Main results:
  • LDH, alkaline phosphatase and protein in BAL were increased in asbestos-exposed rats at 10 and 20 days
  • Angiotensin-converting enzyme was not detected in BAL from either sham controls or asbestos-exposed rats
  • Cell composition of BAL: in control rats over 98% of cells were alveolar macrophages; in asbestos-exposed rats PMNs were about 15-22% and lymphocytes about 5-8% of cell yields
  • Total BAL cell numbers rose with asbestos exposure; the abstract printed in the article states the increase was statistically significant at 20 days
  • Lung hydroxyproline was elevated in asbestos-exposed rats at both 10 and 20 days, more at 20 days than at 10 days
  • Focal fibrotic lesions were already seen at 10 days in asbestos-exposed rats
  • The histologic fibrosis grade in asbestos-exposed rats was not significantly elevated until 20 days
  • Asbestos-exposed rats had more interstitial cells and airspace epithelial cells incorporating 3H-thymidine, while labelled bronchiolar epithelial cells were not significantly increased
• The authors' conclusion: The authors concluded that the model showed a sequence of biochemical, morphologic and proliferative changes, with cell damage and inflammation within 10 days of crocidolite exposure. They also concluded that biochemical detection of collagen synthesis appeared to be a more sensitive tool than histology for measuring incipient fibrotic changes, and they considered these indices useful for testing preventive and therapeutic approaches.
• Limitations the authors state:
  • The authors noted that 3H-thymidine-labelled cells were not confined to areas of fibrosis, so the proliferative responses may not be intrinsically related to fibrogenesis

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Bronchoalveolar Lavage (BAL), Histopathology, BAL Fluid, Interstitial, Fibrosis.

Related studies

• Inhibition of lung injury, inflammation, and interstitial pulmonary fibrosis by polyethylene glycol-conjugated catalase in a rapid inhalation model of asbestosis — B.T. Mossman, J.P. Marsh, et al. (1990)
• Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos — T.R. Quinlan, K.A. BéruBé, et al. (1995)
• Dose-responsive increases in pulmonary fibrosis after inhalation of asbestos — T.R. Quinlan, J.P. Marsh, et al. (1994)
• Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models — T.R. Quinlan, K.A. BeruBe, et al. (1998)
• Persistent localization of activated extracellular signal-regulated kinases (ERK1/2) is epithelial cell-specific in an inhalation model of asbestosis — A.B. Cummins, C. Palmer, et al. (2003)
• Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase — B.T. Mossman, J.P. Marsh, et al. (1986)

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