Oxidant stress responses in human pleural mesothelial cells exposed to asbestos

Our plain-English summary of Oxidant stress responses in human pleural mesothelial cells exposed to asbestos, by Y.M. Janssen, J.P. Marsh, M.P. Absher, et al (American Journal of Respiratory and Critical Care Medicine, 1994).

The study

• Authors: Y.M. Janssen, J.P. Marsh, M.P. Absher, E. Gabrielson, P.J. Borm, K. Driscoll, B.T. Mossman
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 1994;149(3 Pt 1):795-802
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The generation of oxidants is a proposed mechanism of cell injury by asbestos fibers. To determine whether human pleural mesothelial cells (HMC) respond to asbestos and active oxygen species (AOS) by induction of antioxidant enzymes, cells obtained from pleural effusion were exposed to crocidolite or chrysotile asbestos or xanthine/xanthine oxidase (X/XO), a chemical-generating system of AOS. Gene expression of manganese-containing superoxide dismutase (MnSOD) and heme oxygenase (HO), endogenous enzymes involved in cell defense against oxidant stresses, was then determined. Dosage-dependent increases in steady-state mRNA levels of MnSOD and HO were observed in HMC exposed to asbestos or X/XO. However, increases in gene expression of MnSOD or HO did not occur in HMC after exposure to particulates such as polystyrene beads or riebeckite, the nonfibrous analog of crocidolite asbestos. Comparative experiments with human adult lung fibroblasts (HAL) showed less striking increases in mRNA levels of MnSOD and HO in response to asbestos, but steady-state mRNA levels for HO were increased more than fivefold in response to X/XO. To determine whether increases in mRNA levels of MnSOD were translated into protein, Western blot analyses were performed on HMC and HAL cells exposed to asbestos or X/XO. Slight increases in MnSOD immunoreactive protein were observed in HMC in response to both agents. In contrast, X/XO caused striking elevations in MnSOD protein levels in HAL cells. These results suggest that certain antioxidant enzymes are inducible in HMC after exposure to asbestos and other oxidants.

In plain English

This was a laboratory study of human cells grown in dishes. The authors used mesothelial cells (the cells lining the pleura) from the pleural fluid of patients with congestive heart failure and no clinical history of pleural disease, and a line of human adult lung fibroblasts. They exposed the mesothelial cells to crocidolite or chrysotile asbestos, to a chemical system producing reactive oxygen (xanthine plus xanthine oxidase), or to non-fibrous particles (riebeckite or polystyrene beads); the fibroblasts received crocidolite, the chemical system or riebeckite. They measured messenger RNA for two defensive enzymes, manganese superoxide dismutase (MnSOD) and heme oxygenase (HO), and MnSOD protein. In the mesothelial cells, crocidolite raised HO mRNA significantly. Its increases in MnSOD mRNA in the time-course experiment were slight and not statistically significant. The chemical system raised MnSOD mRNA two- to threefold. In one cell isolate, both crocidolite and chrysotile significantly raised MnSOD mRNA. Riebeckite altered neither. MnSOD protein rose modestly. In the fibroblasts, crocidolite did not significantly change either, while the chemical system raised both. The authors concluded that certain antioxidant enzymes are inducible in mesothelial cells after exposure to asbestos and other oxidants.

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) cell culture experiment
• Who was studied: Two isolates of human pleural mesothelial cells (HMC 9015 and 9017), obtained by pleural effusion from patients with congestive heart failure and no clinical history of pleural disease, plus one line of human adult lung fibroblasts (HAL); University of Vermont laboratory
• Exposure: UICC reference samples of crocidolite and chrysotile asbestos; xanthine/xanthine oxidase, a chemical system generating active oxygen species; riebeckite (nonfibrous, chemically similar to crocidolite) and polystyrene beads as negative controls. The mesothelial cells received crocidolite (e.g. 1.25, 2.5 or 5 micrograms per square centimeter of dish), chrysotile (1 microgram per square centimeter), xanthine/xanthine oxidase and riebeckite. The lung fibroblasts received crocidolite (2.5 to 10 micrograms per square centimeter), xanthine/xanthine oxidase and riebeckite. The outcomes measured were steady-state mRNA levels of MnSOD and HO, and MnSOD protein
• Main results:
  • In the toxicity tests, neither cell type showed a change in protein amount after crocidolite at concentrations below 25 micrograms per square centimeter, or after xanthine/xanthine oxidase below 0.2 U/ml
  • In mesothelial cells (HMC 9017), crocidolite caused slight but not statistically significant increases in MnSOD mRNA after 8 and 24 h. Xanthine/xanthine oxidase caused twofold to threefold increases (p less than 0.05)
  • In mesothelial cells, HO gene expression rose after crocidolite (p less than 0.05) and after xanthine/xanthine oxidase (p less than 0.05)
  • In mesothelial cells, crocidolite and xanthine/xanthine oxidase caused dose-dependent increases in HO mRNA, while riebeckite did not alter HO or MnSOD mRNA
  • In mesothelial cell line 9015, MnSOD mRNA rose significantly (p less than 0.05) after both crocidolite and chrysotile. Only crocidolite caused significant increases in HO
  • In mesothelial cells, polystyrene beads and riebeckite did not increase MnSOD or HO gene expression (reported in the article's summary)
  • In mesothelial cells, MnSOD protein showed modest increases at 48 h after crocidolite or xanthine/xanthine oxidase
  • In lung fibroblasts, crocidolite did not significantly alter MnSOD or HO mRNA
  • In lung fibroblasts, xanthine/xanthine oxidase significantly increased MnSOD mRNA at 2 and 8 h, and caused transient increases in HO mRNA (p less than 0.05) at 2 and 4 h. The article's summary describes the HO increase as more than fivefold
  • In lung fibroblasts, crocidolite did not increase MnSOD protein at 24 or 48 h. Xanthine/xanthine oxidase caused small increases at 24 h and more striking increases at 48 h
• The authors' conclusion: The authors concluded that their results suggest certain antioxidant enzymes are inducible in human pleural mesothelial cells after exposure to asbestos and other oxidants. They also concluded that these cells are not compromised in their ability to induce MnSOD or HO gene expression under oxidative stress
• Limitations the authors state:
  • The authors stated that strict comparisons between the two cell types require further study

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Crocidolite, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Pleural Effusion, Crocidolite, Chrysotile, Superoxide, Riebeckite, Fibroblast.

Related studies

• Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos — H. Fung, Y.W. Kow, et al. (1997)
• Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters — B. Kroczynska, R. Cutrone, et al. (2006)
• Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors — K. Pelin, A. Hirvonen, et al. (1995)
• Mechanisms of oxidative stress and alterations in gene expression by Libby six-mix in human mesothelial cells — J.M. Hillegass, A. Shukla, et al. (2010)
• Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats — I.Y. Adamson, H. Prieditis, et al. (1997)
• Modulation of genotoxic effects in asbestos-exposed primary human mesothelial cells by radical scavengers, metal chelators and a glutathione precursor — I. Poser, Q. Rahman, et al. (2004)

Browse more research in American Journal of Respiratory and Critical Care Medicine, or return to medical research.