Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells

Our plain-English summary of Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells, by B. Keeling, K.Y. Li, A. Churg (American Journal of Respiratory Cell and Molecular Biology, 1994).

The study

• Authors: B. Keeling, K.Y. Li, A. Churg
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1994;10(6):683-8
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The factors that determine whether an exogenous mineral particle will be taken up by tracheobronchial epithelial cells are unclear. We have previously proposed that active oxygen species play a role in this process, most likely through iron-catalyzed formation of hydroxyl radical and subsequent lipid peroxidation of cell membranes. To further examine this hypothesis, we prepared rat tracheal explant cultures and exposed them for 1 h to suspensions of amosite asbestos or titanium dioxide (rutile) that had been preincubated with varying concentrations of a mixture of ferrous and ferric chloride. Explants were then maintained in organ culture in air/CO2 for 1 wk to allow particle or fiber uptake to occur. Particles or fibers in the tracheal epithelium were determined by light microscopic morphometry. Similarly treated explants were assayed for malondialdehyde as a measure of lipid peroxidation in the epithelial cells. Asbestos fibers without added iron caused lipid peroxidation, but this was not true of titanium dioxide particles. For both types of dust, increasing adsorbed iron concentrations were associated with increasing particle uptake and increasing lipid peroxidation. These observations suggest that cationic iron may play a major role in particle uptake by tracheobronchial epithelia, and that particle uptake is also related to iron-mediated lipid peroxidation.

In plain English

This was a laboratory experiment on windpipe segments (tracheal explants) from female Sprague-Dawley rats. The authors tested whether iron added to dust particles changed how many particles the lining cells took up, and how much lipid peroxidation (oxidative damage to cell membranes, measured as malondialdehyde) occurred. Segments were exposed for 1 hour to amosite asbestos or titanium dioxide (rutile) that had been soaked in iron chloride solutions of 0 to 10 mM, then kept in culture for 7 days. For amosite, fiber uptake rose significantly at the 1 and 10 mM iron levels but not at 100 µM. Amosite without added iron produced a statistically significant, approximately 2-fold rise in malondialdehyde compared with undusted control segments. Titanium dioxide alone did not raise malondialdehyde compared with undusted controls, and statistically significant increases in its uptake and malondialdehyde were seen only at 10 mM iron. The authors concluded that iron may play a major role in particle uptake. They cautioned that uptake and lipid peroxidation rising together does not prove one causes the other, and that direct translation to whole animals is difficult.

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: Laboratory (in vitro) experiment using rat tracheal explants kept in organ culture
• Who was studied: Tracheal segments from 250-g female Sprague-Dawley rats, with six to 12 segments per test group, studied at the University of British Columbia, Vancouver. Control segments were not exposed to any dust.
• Exposure: UICC standard reference amosite asbestos (4 mg/ml) or titanium dioxide (rutile, 5 mg/ml). The dust was preincubated for 24 h in 0 to 10 mM of an equimolar ferrous/ferric chloride mixture and washed. Segments were exposed to it for 1 h and then cultured for 7 days. The amosite fibers had a geometric mean length of 3.8 µm and width of 0.26 µm.
• Main results:
  • Amosite: fiber uptake by the tracheal lining increased significantly with the 1 mM and 10 mM iron concentrations, but not with 100 µM.
  • Amosite without added iron: a statistically significant, approximately 2-fold increase in malondialdehyde compared with undusted control segments. Malondialdehyde rose markedly with 1 mM and 10 mM iron.
  • Titanium dioxide: statistically significant increases in particle uptake and malondialdehyde were seen only at the 10 mM iron dose. Titanium dioxide by itself produced no evidence of lipid peroxidation compared with controls.
  • Surface iron: untreated titanium dioxide had virtually no surface iron, while untreated amosite had considerably more. Each successive iron loading dose significantly increased surface iron on both dusts.
• The authors' conclusion: The authors concluded that cationic iron may play a major role in particle uptake by tracheobronchial lining cells, and that particle uptake is also related to iron-mediated lipid peroxidation. They described this as only some support for a role of lipid peroxidation.
• Limitations the authors state:
  • The fact that particle uptake and lipid peroxidation changed together does not prove that lipid peroxidation causes uptake.
  • Whole segments were homogenized, so the malondialdehyde assay may have measured changes in cells beneath the lining layer. The authors thought this probably not a significant problem.
  • The surface iron levels reached on titanium dioxide were considerably higher than those found on dust recovered from lungs, so this part of the experiment might be unphysiologic.
  • Direct translation of the findings to the whole animal is difficult, and the in vitro model may somewhat exaggerate the effects of surface iron.

Topics

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

Medical terms in this study, explained in our Lexicon: Hydroxyl Radical, Amosite, Epithelium.

Related studies

• Cigarette smoke increases amosite asbestos fiber binding to the surface of tracheal epithelial cells — A. Churg, J. Sun, et al. (1998)
• Effect of mineral particles containing iron on primary cultures of rabbit tracheal epithelial cells: possible implication of oxidative stress — C. Guilianelli, A. Baeza-Squiban, et al. (1993)
• Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture — A. Churg, M. Brauer, et al. (1996)
• Effects of cigarette smoke on epithelial uptake of non-asbestos mineral particles in tracheal organ culture — B. Keeling, J. Hobson, et al. (1993)
• Relationship of fiber surface iron and active oxygen species to expression of procollagen, PDGF-A, and TGF-beta(1) in tracheal explants exposed to amosite asbestos — J. Dai, A. Churg (2001)
• Active oxygen species mediate asbestos fiber uptake by tracheal epithelial cells — J. Hobson, J.L. Wright, et al. (1990)

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