Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases

Our plain-English summary of Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases, by Y. Nishimura, M. Maeda, N. Kumagai-Takei, et al (Environmental Health and Preventive Medicine, 2013).

The study

• Authors: Y. Nishimura, M. Maeda, N. Kumagai-Takei, S. Lee, H. Matsuzaki, Y. Wada, T. Nishiike-Wada, H. Iguchi, T. Otsuki
• Journal: Environmental Health and Preventive Medicine
• Published: 2013;18(3):198-204
• Type of article: Review
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. We focused on alveolar macrophages (AM) and natural killer (NK) cells in asbestosis and mesothelioma, respectively, and examined their functions upon exposure to asbestos or in patients with mesothelioma. Exposure to asbestos caused rat AM to exhibit high production of transforming growth factor-beta (TGF-β) with prolonged survival in the absence of other cells, not simultaneously with the apoptosis caused by asbestos. The NK cell line showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, and primary NK cells in culture with asbestos and peripheral blood NK cells in mesothelioma shared a decrease in expression of NKp46, a representative activating receptor. The AM finding indicates that AM contribute to asbestosis by playing a direct role in the fibrogenic response, as well as the inflammatory response. The response of NK cells indicates that exposure to asbestos has an immune-suppressive effect, as well as a tumorigenic effect. Our studies therefore reveal novel effects of asbestos exposure on AM and tumor immunity, which may represent valuable information for construction of a strategy for prevention and cure of asbestosis and malignant mesothelioma.

In plain English

This article was a review in which the authors summarized their own earlier laboratory studies on how chrysotile B asbestos affects two kinds of immune cells: alveolar macrophages (lung scavenger cells), which they linked to asbestosis, and natural killer (NK) cells, which they linked to malignant mesothelioma. In rats given chrysotile B into the windpipe, lung fluid showed inflammation after 1 day and more TGF-beta, a scarring-related signal, after 5 days. Macrophages exposed to low doses produced more TGF-beta and showed signs of longer survival, while higher doses caused cell death. A human NK cell line kept with chrysotile for about 5 months lost some of its ability to kill target cells. NK cells from mesothelioma patients, and NK cells cultured with chrysotile, both showed less of a receptor called NKp46. Glass wool did not cause this decrease. The authors concluded that macrophages may play a direct role in lung scarring and that asbestos may suppress immunity in ways that might contribute to mesothelioma. They noted that the cell-line results did not match the patient results.

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: Review of the authors' own previous laboratory studies (rat experiments, cell culture experiments, and blood NK cells from patients and healthy volunteers)
• Who was studied: Wistar rats and their alveolar macrophages; a human NK cell line (YT-A1); blood NK cells from healthy volunteers and from patients with malignant mesothelioma. The review does not give the number of animals or people.
• Exposure: Chrysotile B asbestos. Rats received 4 mg into the trachea. Macrophages were exposed in culture to 1.25 to 25 micrograms per square centimeter. The NK cell line was kept long term at 5 micrograms per ml. Blood mononuclear cells were cultured at 5 micrograms per ml for 7 days. Glass wool, a man-made mineral fiber, was used as a comparison.
• Main results:
  • In rats given chrysotile B, lung lavage fluid 1 day later showed more granulocytes and the inflammatory signals TNF-alpha, IL-1beta and IL-6 than in control rats. At 5 days TGF-beta was increased and many apoptotic (dying) cells were found.
  • Macrophages from chrysotile-exposed rats produced high levels of TGF-beta, and further exposure in culture did not raise this. Macrophages from control rats produced little, but exposure in culture raised their TGF-beta to the same level.
  • Macrophages died (apoptosis) at 12.5 or 25 micrograms per square centimeter but not at 1.25 or 2.5. TGF-beta production peaked at 2.5 and did not increase above 5.0. The macrophages also showed increased expression of the survival-related genes Bcl-2 and Bcl-xL.
  • The chrysotile-exposed NK cell line (YT-CB5) did not differ from the control line at 1 month. After about 5 months it showed lower ability to kill target cells, with decreased expression of the receptors NKG2D and 2B4 but not NKp46. Activation of the signaling molecule ERK after NKG2D stimulation was also lower.
  • Blood NK cells from patients with malignant mesothelioma showed impaired killing ability, with decreased NKp46 but not NKG2D or 2B4.
  • NK cells in blood cell cultures exposed to chrysotile B showed decreased NKp46, but not NKG2D or 2B4, as seen in the patients. Glass wool did not cause a decrease in NKp46.
• The authors' conclusion: The authors concluded that alveolar macrophages may contribute directly to the scarring (fibrogenic) response in asbestosis, not only to inflammation. They also concluded that asbestos has an immune-suppressive effect on NK cells that might contribute to the development of malignant mesothelioma, alongside its tumor-causing effect.
• Limitations the authors state:
  • Results from the NK cell line did not match those from primary NK cell cultures or from mesothelioma patients. The cell line did not show the decrease in NKp46.
  • The amount of TGF-beta produced by the macrophages may not be large.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Asbestos Exposure, Malignant Mesothelioma, Mesothelioma, Transforming Growth Factor-beta (TGF-β), Apoptosis, Fibrogenic.

Related studies

• Long-lasting production of TGF-beta1 by alveolar macrophages exposed to low doses of asbestos without apoptosis — Y. Nishimura, T. Nishiike-Wada, et al. (2007)
• A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function — R.F. Hamilton, A. Holian, et al. (2004)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)
• Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury — D.W. Kamp, M.M. Dunn, et al. (1994)
• Activation of alveolar macrophages and peripheral red blood cells in rats exposed to fibers/particles — F. Afaq, P. Abidi, et al. (1998)
• 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)

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