Experimental lesions in rats corresponding to advanced human asbestosis

Our plain-English summary of Experimental lesions in rats corresponding to advanced human asbestosis, by J.M. Davis, R.E. Bolton, D. Brown, et al (Experimental and Molecular Pathology, 1986).

The study

• Authors: J.M. Davis, R.E. Bolton, D. Brown, H.E. Tully
• Journal: Experimental and Molecular Pathology
• Published: 1986;44(2):207-21
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Rats inhaling chrysotile asbestos developed a progressive interstitial fibrosis similar in most respects to human asbestosis. The earliest lesions were focal deposits of fibrous tissue in the walls of respiratory bronchioles and alveolar ducts. Later alveolar septa between adjacent bronchioles became progressively thickened to produce lesions with similarities to human honeycombing. The thickened septa between alveoli or "micro-honeycomb" spaces were mainly surfaced with cuboidal epithelial cells although some spaces lined by ciliated columnar epithelium were also found. Transmission electron microscopy of these advanced lesions showed that the cuboidal epithelial cells retained most of the characteristics of type 2 pneumocytes but that they frequently exhibited apical cytoplasmic blebs normally associated with the apocrine secretion of Clara cells. Columnar cells exhibited all stages from fully cilitated to cells with only an occasional cilium among the normal cell surface microvilli. Alveolar or micro-honeycomb spaces frequently contained clusters of pulmonary macrophages with their surface processes interdigitated but with no signs of fusion to giant cells. At more than 18 months after the end of dust inhalation these macrophages contained no chrysotile asbestos. The basement membranes beneath the epithelial layers of thickened septa were irregular and often convoluted as well as being much thicker than normal. Microscopic deposits of calcification were frequently found within the basement membrane material. Some thickened septa were relatively acellular, consisting mainly of masses of collagen fibrils but others were cellular and contained many macrophages, fibroblasts, plasma cells and mast cells. In these advanced lesions extremely little chrysotile asbestos was found and this was present in two sites only. Some chrysotile, always as individual fibrils and usually of short length, was present among collagen fibrils in areas of fibrosis and some was present within the thickened basement membranes.

In plain English

This animal experiment, from the Institute of Occupational Medicine in Edinburgh, used light and electron microscopy to examine lung tissue from elderly rats. The rats had inhaled chrysotile asbestos dust at 4 mg/m3 for 1 year and were killed at various times between the end of exposure and 19 months later. The article does not state how many rats were examined. Advanced lung scarring (fibrosis) was uncommon until 6 months after exposure ended but was found in all animals older than 2½ years. Similar changes were seen only very occasionally in old control rats. Scarred areas formed small thick-walled spaces, termed "micro-honeycomb" by the authors, resembling human honeycombing. Most lining cells resembled type 2 pneumocytes; some spaces were lined with ciliated cells. In these advanced lesions, clustered macrophages did not appear to fuse into giant cells. Basement membranes were thickened and irregular, with small calcium deposits. Very little chrysotile was found. It appeared as single fibrils almost only among collagen in scarred areas and in thickened basement membranes; just one fibril was found inside a macrophage. The authors concluded that the rat appears to be a good model for studying asbestosis.

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: light and transmission electron microscopy (TEM) examination of rat lung tissue taken from a long-term inhalation study
• Who was studied: Rats of advanced age (2½ to 3 years old) from a long-term chrysotile inhalation study at the Institute of Occupational Medicine, Edinburgh, Scotland; the number of rats examined is not stated
• Exposure: Inhaled dust from several different preparations of chrysotile asbestos at 4 mg/m3 of air for 1 year; rats were killed at various times from the end of dusting up to 19 months later
• Main results:
  • In chrysotile-treated rats, advanced fibrosis was first seen in small areas in occasional rats at the end of the 12-month dusting period. It was uncommon until 6 months after dusting ended and was found in all animals aged more than 2½ years.
  • Similar changes were seen very occasionally in control rats, but only in advanced age and at levels usually more than two orders of magnitude less than after chrysotile treatment.
  • Thick-walled spaces formed that were histologically similar to human honeycombing, but without the same widespread increase in size; the authors called them "micro-honeycomb" spaces.
  • The cuboidal cells lining many micro-honeycomb spaces showed most of the structural features of type 2 pneumocytes. Some had large apical cytoplasmic blebs, which the authors likened to the apocrine secretion of Clara cells.
  • Occasional areas were lined by ciliated columnar cells. In some areas there was a gradation from fully ciliated cells to cells with a few cilia to typical type 2 pneumocytes.
  • In the advanced lesions in old rats, alveolar macrophages often formed tightly bound clusters in the spaces, but they did not appear to fuse into giant cells.
  • Basement membranes beneath the lining cells were irregular, convoluted and often much thicker than normal. The thickened areas often contained small nodules of calcification.
  • Some thickened septa were mainly acellular connective tissue. Others contained many cells, mostly fibroblasts, with macrophages, mast cells and plasma cells also common.
  • Very little chrysotile was found. It was present as individual fibrils almost exclusively among collagen fibers in fibrotic areas and within thickened basement membrane.
  • Across sections from many tissue blocks, only one chrysotile fibril was found within an alveolar macrophage.
• The authors' conclusion: The authors concluded that the rat appears to be a good model for experimental studies of asbestosis, with stages of fibrosis development similar to those found in humans.
• Limitations the authors state:
  • The mass of chrysotile remaining in the lungs of 3-year-old rats was not measured; the authors judged it to be extremely small only from how hard it was to find by electron microscopy.
  • Electron microscopy could not be used to compare advanced lesions in amphibole-treated rats, because the tough amphibole fibers are difficult to section.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Interstitial Fibrosis, Honeycombing, Alveoli, Epithelium, Transmission Electron Microscopy (TEM), Columnar Cell, Macrophage.

Related studies

• Experimental asbestosis. The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust — P. Gross, R.T. DeTreville, et al. (1967)
• Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats — E. Fasske (1988)
• 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)
• Time course of chemotactic factor generation and the corresponding macrophage response to asbestos inhalation — D.B. Warheit, L.H. Hill, et al. (1986)
• Epithelial outgrowths from lung tissue following intrapleural injection of asbestos dust in experimental animals — J.M. Davis (1971)
• Characteristics of tumors and tumor cells cultured from experimental asbestos-induced mesotheliomas in rats — J.E. Craighead, N.J. Akley, et al. (1987)

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