Effects of cigarette smoke exposure on retention of asbestos fibers in various morphologic compartments of the guinea pig lung

Our plain-English summary of Effects of cigarette smoke exposure on retention of asbestos fibers in various morphologic compartments of the guinea pig lung, by A. Churg, V. Tron, J.L. Wright (The American Journal of Pathology, 1987).

The study

• Authors: A. Churg, V. Tron, J.L. Wright
• Journal: The American Journal of Pathology
• Published: 1987;129(2):385-93
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

For investigation of mechanisms whereby smoking might potentiate asbestos-related disease, guinea pigs were given 0.5 mg UICC amosite by intratracheal instillation. Half the animals were subsequently exposed to cigarette smoke. Animals were sacrificed at 1 day, 7 days, and 1 month after exposure. Lungs were lavaged and macrophages separated from the lavage fluid. Lung fiber concentration, numbers of fibers in macrophages, and fiber sizes from tissue (TFs), macrophages (MFs), and macrophage-free lavagate (FFs) were determined by electron microscopy. Smoke-exposed animals retained greater numbers of fibers in lung tissue by 1 month but had greater total numbers of fibers in macrophages at all time periods. In both smokers and nonsmokers, fibers in the three morphologic compartments had distinctly different lengths: the longest fibers were found associated with the lung tissue; the macrophages always contained the shortest fibers; and the macrophage-free lavagate had fibers of intermediate size. However, fiber widths and aspect ratios did not show the same clear separation by anatomic compartment, suggesting that in both smoking and nonsmoking animals length is the size parameter which is most important in determining fiber clearance. Smoking did not affect the lengths of MFs but did produce a progressive reduction in the lengths of FFs and TFs with time. These data indicate that smoking causes a marked increase in the number of fibers retained in the lung within macrophages and suggest that either macrophage removal via the mucociliary escalator or macrophage mobility is impaired by cigarette smoke. However, smoking does not change the sizes of fibers in macrophages and does not appear to depress phagocytic capacity. These observations imply that failure of macrophage clearance and subsequent re-release of fibers into the medium may at least partially explain the changes in fiber sizes and eventual increases in tissue fiber concentrations in smoke-exposed animals.

In plain English

This animal experiment examined how cigarette smoke affects where amosite asbestos fibers end up in the lung. Thirty female guinea pigs each had 0.5 mg of UICC amosite placed directly into the windpipe, and half were then exposed to cigarette smoke. Groups of five were killed at 1 day, 1 week and 1 month. The authors measured fiber concentration in lung tissue, fiber numbers in macrophages (scavenger cells) washed from the lung, and fiber sizes in tissue, macrophages and the remaining wash fluid. Between 1 week and 1 month, tissue fiber concentration fell fivefold in unexposed animals but less than twofold in smoke-exposed animals, and the two groups differed at 1 month. Smoke-exposed animals had statistically much greater total numbers of fibers in macrophages at all time points. Macrophages held the shortest fibers and tissue mostly the longest, and smoke did not change macrophage fiber lengths. The authors proposed that failing macrophage clearance helps explain the findings, and they called this scheme purely hypothetical. They noted that placing asbestos in the windpipe differs from inhaling it, and that lung washing did not remove all macrophages.

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: guinea pigs given amosite asbestos into the trachea, with half then exposed to cigarette smoke and half not, compared at three time points
• Who was studied: Thirty 400-g Hartley strain female guinea pigs, studied at the University of British Columbia, Vancouver. Groups of 5 smoke-exposed or 5 non-exposed animals were killed at 1 day, 1 week and 1 month after asbestos instillation.
• Exposure: 0.5 mg UICC amosite asbestos by intratracheal instillation. Smoke-exposed animals received the whole smoke of 10 nonfilter cigarettes, 5 days a week, roughly 100 minutes per day, starting 12 hours after asbestos instillation.
• Main results:
  • Lung tissue fiber concentration, between 1 week and 1 month: in non-smoke-exposed animals it dropped fivefold (P less than 0.03). In smoke-exposed animals it dropped less than twofold (not significant). The two groups were statistically different at 1 month (P less than 0.05).
  • Fiber concentration in macrophages (fibers per million macrophages): at 1 month, non-exposed animals had about one quarter of the mean concentration of smoke-exposed animals (P less than .03).
  • Total numbers of fibers in macrophages were statistically much greater in smoke-exposed animals at all time points.
  • Macrophages, in both groups: they consistently contained the shortest fibers, with geometric mean lengths of about 2 micrometres. Mean length did not change significantly over time and did not differ between smoke-exposed and non-exposed animals.
  • Fibers associated with lung tissue were, for the most part, significantly longer than fibers in macrophages or in the macrophage-free wash fluid.
  • Fibers in the macrophage-free wash fluid were intermediate in length between macrophage fibers and tissue fibers.
  • Tissue fiber length at 1 month: it had increased in non-exposed animals and was much longer than in smoke-exposed animals, where it had markedly decreased (P less than 0.01 between groups).
  • Fiber widths and aspect ratios followed broadly similar trends, but the differences between lung compartments were not as clear as for length.
• The authors' conclusion: The authors concluded that a likely mechanism of asbestos fiber retention in this animal model is a rapidly developing failure of macrophage clearance, with fibers building up in macrophages. They described their overall scheme as purely hypothetical and said that interference with macrophage clearance may be only one of several mechanisms operating in smoke-exposed animals.
• Limitations the authors state:
  • Asbestos was given by intratracheal instillation rather than inhalation. This method is known to produce uneven fiber distribution in the lung and may have influenced the results.
  • Only 3 lung washes were used, giving a relatively low macrophage yield. The method therefore cannot measure the actual number of fibers in the whole macrophage compartment.
  • Tissue fiber lengths were diluted by shorter fibers from macrophages and free fibers left in the lung, so the size differences between compartments are underestimated.
  • The data show fibers 'associated' with tissue. They do not by themselves show that fibers actually penetrated tissue.
  • The proposed mechanism is purely hypothetical. It does not explain how some longer fibers are cleared, why free and tissue fiber lengths stay greater than macrophage fiber lengths in smoke-exposed animals, or whether smoke directly affects fiber penetration into tissue.

Topics

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

Medical terms in this study, explained in our Lexicon: UICC, Amosite, Macrophage, Aspect Ratio (Length-to-diameter ratio), Fiber Clearance, Mucociliary Clearance.

Related studies

• Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig — V. Tron, J.L. Wright, et al. (1987)
• Effects of cigarette smoke on tissue uptake and retention of iron oxide in the guinea pig — B. Gilks, J. Wright, et al. (1988)
• Cigarette smoke increases amosite asbestos fiber binding to the surface of tracheal epithelial cells — A. Churg, J. Sun, et al. (1998)
• Effects of cigarette smoke on the clearance of short asbestos fibres from the lung and a comparison with the clearance of long asbestos fibres — A. Churg, J.L. Wright, et al. (1992)
• Effects of cigarette smoke and asbestos on airway, vascular and mesothelial cell proliferation — H. Sekhon, J. Wright, et al. (1995)
• Cigarette smoke increases the penetration of asbestos fibers into airway walls — D. McFadden, J. Wright, et al. (1986)

Browse more research in The American Journal of Pathology, or return to medical research.