Asbestos directly increases lung epithelial permeability

Our plain-English summary of Asbestos directly increases lung epithelial permeability, by M.W. Peterson, M.E. Walter, T.J. Gross (The American Journal of Physiology, 1993).

The study

• Authors: M.W. Peterson, M.E. Walter, T.J. Gross
• Journal: The American Journal of Physiology
• Published: 1993;265(3 Pt 1):L308-17
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos causes the fibrotic lung disease asbestosis, but the biologic basis for this is unknown. Lung epithelial dysfunction including increased permeability is hypothesized to contribute to lung scarring in other forms of pulmonary fibrosis. Lung epithelial permeability is increased in both animals and humans exposed to asbestos. It is not known whether the increased epithelial permeability results from direct effects of asbestos or occurs as a result of the inflammatory reaction to asbestos fibers. To address this question we used a cultured human lung epithelial model, and we measured the direct effect of asbestos on lung epithelial barrier integrity as measured by mannitol permeability. We exposed the monolayer to chryogenically ground, respirable-sized chrysotile asbestos particles. This chrysotile asbestos caused a dose- and time-dependent increase in mannitol permeability across the epithelial monolayer. Increased mannitol permeability occurred both in the presence and in the absence of serum, was not due to cytotoxicity as measured by lactate dehydrogenase release, and was not associated with altered actin cytoskeleton at the light microscopic level. Permeability to 70 kDa neutral dextran also increased after asbestos exposure; however, the absolute permeability to dextran was less than mannitol permeability. Neither latex beads nor tantalum caused any change in permeability, suggesting that our findings are not explained by nonspecific effects of particles. Increased permeability did not reverse in the continued presence of asbestos and persisted even after removing the asbestos. Finally, surface-bound iron did not appear to be necessary for this effect because neither chelating iron with deferoxamine nor iron-loading the asbestos altered the effect on mannitol permeability. These results show that asbestos has direct effects on lung epithelial permeability. Together with the recent observation that asbestos directly increases epithelial fibrinolytic activity, our results suggest a novel mechanism for asbestos-induced lung injury.

In plain English

This laboratory study tested whether asbestos could make a layer of human airway lining cells leakier on its own, without the inflammatory cells present in a living lung. The authors grew a human bronchial epithelial cell line as single cell layers on filters. They exposed these layers to chrysotile asbestos (Calidria) ground into respirable particles with a mean length of 1 micrometer. Leakiness was measured as how much of a small molecule, mannitol, crossed the layer. At 100 or 500 micrograms per milliliter, mannitol permeability rose fourfold 19 hours after asbestos was added. After 24 hours of exposure, there was no increase at 1 microgram per milliliter, and the increase was maximal at 50. Permeability to a larger molecule, dextran, doubled. Asbestos did not increase release of the enzyme LDH, a marker of cell damage. Latex beads and tantalum particles did not change permeability. Permeability kept rising with longer exposure and after the asbestos-containing medium was removed. Changing the iron on the fiber surfaces did not alter the effect. The authors concluded that chrysotile asbestos directly increased epithelial permeability in this model.

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: In vitro (cell culture) laboratory experiment
• Who was studied: A human bronchial epithelial cell line (HBE), derived from human segmental bronchial epithelial cells transformed with SV40 large T antigen, grown as cell monolayers on filters; no humans or animals were studied
• Exposure: Chrysotile asbestos (Calidria, Union Carbide), cryogenically ground to a mean particle length of 1 micrometer, applied at 1 to 500 micrograms per milliliter, mostly for 24 hours; latex beads and tantalum were used as comparison particles
• Main results:
  • Mannitol permeability of the cell layers rose fourfold 19 hours after adding 100 or 500 micrograms per milliliter of asbestos, and stayed at that level at 24 hours
  • After 24 hours of exposure, permeability did not increase at 1 microgram per milliliter of asbestos but increased maximally at 50 micrograms per milliliter
  • Permeability to the larger molecule dextran (70 kD) doubled after asbestos exposure; mannitol permeability rose fourfold in the same experiments
  • Release of the enzyme LDH, a marker of cell damage, was not changed by 100 or 500 micrograms per milliliter of asbestos, with or without serum
  • Asbestos had no visible effect on cell shape or on the actin cytoskeleton under the light microscope
  • Permeability increased only in cell layers exposed to asbestos, not in those exposed to latex beads or tantalum
  • Permeability continued to increase with longer exposure, measured at 24, 48 and 72 hours
  • Permeability continued to increase 24 and 48 hours after the asbestos-containing medium was removed
  • Neither chelating surface iron with deferoxamine nor iron-loading the fibers affected the rise in permeability. Deferoxamine reduced surface iron by 70% and iron-loading increased it sixfold.
• The authors' conclusion: The authors concluded that, in an in vitro human lung epithelial model, chrysotile asbestos fibers directly increased epithelial permeability, without cell death, and that asbestos may contribute to lung disease without requiring inflammatory cells.
• Limitations the authors state:
  • The authors noted that the rise in permeability after the asbestos was removed may be because the cells had taken up fibers that washing could not fully remove
  • The authors stated that whether the effect depends on oxidant production was unresolved and needs further study

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Santa Rita mine, Joaquin Ridge near Coalinga, California

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Pulmonary Fibrosis, Chrysotile, Lactate Dehydrogenase (LDH), Asbestos Exposure.

Related studies

• Cigarette smoke increases amosite asbestos fiber binding to the surface of tracheal epithelial cells — A. Churg, J. Sun, et al. (1998)
• Asbestos-induced lung epithelial permeability: potential role of nonoxidant pathways — M.W. Peterson, J. Kirschbaum (1998)
• Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells — B. Keeling, K.Y. Li, et al. (1994)
• Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall — J. Dai, B. Gilks, et al. (1998)
• Asbestos exposure increases paracellular transport of fibrin degradation products across human airway epithelium — T.J. Gross, S.M. Cobb, et al. (1994)
• Asbestos exposure increases human bronchial epithelial cell fibrinolytic activity — T.J. Gross, S.M. Cobb, et al. (1993)

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