Asbestos stimulation triggers differential cytokine release from human monocytes and alveolar macrophages

Our plain-English summary of Asbestos stimulation triggers differential cytokine release from human monocytes and alveolar macrophages, by L.J. Geist, L.S. Powers, M.M. Monick, et al (Experimental Lung Research, 2000).

The study

• Authors: L.J. Geist, L.S. Powers, M.M. Monick, G.W. Hunninghake
• Journal: Experimental Lung Research
• Published: 2000;26(1):41-56
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation of asbestos fibers results in a variety of lung diseases, including pulmonary fibrosis. Various animal models have demonstrated the importance of cytokines in the pathogenesis of pulmonary fibrosis. Alveolar macrophages from patients exposed to asbestos spontaneously release increased amounts of cytokines. The purpose of these studies was to determine whether asbestos directly stimulates cytokine release from human alveolar macrophages after in vitro exposure. We demonstrate that, although asbestos triggers cytokine release from blood monocytes, normal alveolar macrophages do not respond to asbestos stimulation with cytokine release. However, normal alveolar macrophages are activated by asbestos particles, in vitro, as determined by the upregulation of mRNAs for cytokines, and activation of the p38 kinase, which has been shown to be important in the translation of cytokine message into protein. These studies demonstrate that asbestos stimulates both normal blood monocytes and normal alveolar macrophages, but that there is a block in translation of cytokine mRNAs in the macrophages.

In plain English

This laboratory study exposed human cells to asbestos. From the same healthy, nonsmoking volunteers, the authors collected alveolar macrophages by lung washing during bronchoscopy, and blood cells that were about 20% monocytes, the rest lymphocytes. The cells received amosite, crocidolite or chrysotile asbestos, or LPS as a positive control. Each asbestos type significantly increased release of three inflammatory proteins (TNF, IL-6 and IL-8) from the monocyte preparations. It did not raise their release from alveolar macrophages above control levels. Yet asbestos raised the macrophages' messenger RNA for IL-6 and IL-8 to levels similar to those with LPS. Nor were the proteins building up inside the macrophages. Asbestos also activated the enzyme p38 kinase in the macrophages, which the authors said could not explain the gap. Cytokine release did not appear to differ by fiber type, so later tests used amosite only. The authors concluded that the block lay in translating RNA into protein. They suggested that recruitment of immature macrophages or monocytes to the lung, and/or a change in the fibers' capacity to stimulate cells, may be important in 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: In vitro laboratory experiment on human cells (blood mononuclear cells and alveolar macrophages) exposed to asbestos in culture
• Who was studied: Alveolar macrophages obtained by bronchoalveolar lavage, and blood mononuclear cells, from healthy nonsmoking volunteers without asbestos exposure or other lung diseases (University of Iowa). Both cell types came from the same volunteer in each experiment. The blood preparation was approximately 20% monocytes, with the remainder lymphocytes, and was plated according to monocyte numbers. The total number of volunteers is not stated in the text.
• Exposure: Amosite, crocidolite and chrysotile asbestos (endotoxin-free preparations from the NAIMA Fiber Repository), each at 50 (printed 'm g/mL') in the cytokine release experiments. Only amosite, at 500 (same unit), was used in the RNA experiments. LPS was used as a positive control.
• Main results:
  • In alveolar macrophages, asbestos did not increase release of TNF, IL-6 or IL-8 over unstimulated control cells.
  • In blood monocytes (a mixed preparation of about 20% monocytes and the rest lymphocytes), each form of asbestos produced a statistically significant (P less than .05) increase in release of TNF, IL-6 and IL-8.
  • Asbestos did not trigger cytokine release from alveolar macrophages with or without serum, or when the cells could adhere to plastic dishes. It continued to trigger release from monocytes.
  • Amosite asbestos increased IL-6 and IL-8 messenger RNA in alveolar macrophages, in amounts comparable to those induced by LPS.
  • At 3, 6 and 24 hours, alveolar macrophages stimulated with asbestos expressed similar amounts of IL-6 and IL-8 messenger RNA to those stimulated with LPS.
  • There was no increase in cytokines held inside the alveolar macrophages compared with monocytes, so the missing release was not due to proteins being retained in the cells.
  • Asbestos activated p38 kinase in alveolar macrophages, to a similar degree as LPS. The authors stated that this could not account for the translational block.
  • The authors located the defect in cytokine release by alveolar macrophages at the step of translating cytokine messenger RNA into protein.
  • Cytokine release did not appear to differ by type of asbestos, so the remaining experiments (messenger RNA and p38 kinase) used amosite only.
• The authors' conclusion: The authors concluded that asbestos increases cytokine production from peripheral blood mononuclear cells but not from alveolar macrophages, and that the difference occurs where messenger RNA is translated into protein. They suggested that recruitment of immature macrophages/monocytes to the lung and/or a change in the capacity of the fibers to stimulate cells may be an important component of the pathogenesis of asbestosis.

Topics

Medical terms in this study, explained in our Lexicon: Cytokine, Alveolar Macrophage, Pulmonary Fibrosis, Macrophage.

Related studies

• Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure — R.C. Perkins, R.K. Scheule, et al. (1993)
• Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts — I. Lemaire, S. Ouellet (1996)
• Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release — G.D. Leikauf, S.P. Fink, et al. (1995)
• Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes — T.O. Khaliullin, E.R. Kisin, et al. (2020)
• High levels of catalase and glutathione peroxidase activity dampen H2O2 signaling in human alveolar macrophages — A.B. Carter, L.A. Tephly, et al. (2004)
• Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation — E. Meunier, A. Coste, et al. (2012)

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