Immune cell type
Kinds of asbestos fiber for exposure or analyzed patients exposed to asbestos
Findings
References
NK cell
Human NK cell line, YT-A1
Cultivation with chrysotile
Reduction of cytotoxicity
Reduction of surface expression of NKG2D and 2B4
Decreased phosphorylation of ERK signaling molecule
Peripheral CD56+ NK cells
Malignant mesothelioma
Low cytotoxicity
Low surface expression of NKp46-activating receptor
Freshly isolated NK cells derived from healthy donors
Cultivation with chrysotile during in vitro activation
Reduction of surface expression of NKp46
Cytotoxic T cell
Human CD8+ cells in mixed lymphocyte reaction (MLR)
Cultivation with chrysotile during MLR
Reduction of allogenic cell killing
Decrease of intracellular IFN-γ and granzyme B
Peripheral CD8+ T cell
Pleural plaque
Relatively high perforin+ cell
T helper cell
Human T cell line, MT-2
Continuous cultivation with chrysotile
Acquisition of asbestos-induced apoptosis
Excess expression and production of IL-10
Overexpression of Bcl-2
Reduced production of IFN-γ, TNF-α, and CXCL10
Reduction of CXCR3 surface and mRNA expressions
Hyperphosphorylation of β-actin
Excess binding capacity to chrysotile in vimentin, myosin 9, and tubulinβ2
Excess production of TGFβ with phosphorylation of p38 and SMAD3
Resistance to TGFβ-induced growth inhibition
Continuous cultivation with crocidolite
Acquisition of asbestos-induced apoptosis
Excess expression and production of IL-10
Enhancement of Bcl-2/Bax expression ratio
Reduced production of IFN-γ and TNF-α
Freshly isolated CD4+ cells derived from healthy donors
Cultivation with chrysotile during in vitro activation
Reduced expression of surface CXCR3
Reduction of intracellular IFN-γ
Peripheral CD4+ T cell
Pleural plaque
Low expression of surface CXCR3
Malignant mesothelioma
Remarkably lower expression of surface CXCR3
Low IFN-γ mRNA expression
High Bcl-2 mRNA expression
Regulatory T cell
[41]
Human T cell line, MT-2
Continuous cultivation with chrysotile
Enhanced suppressive activity in cell-cell contact assay
Enhanced production of functional soluble factors such as IL-10 and TGFβ
Fig. 1.1
Summarized schematic effects of asbestos fibers on various immune cells such as natural killer (NK), cytotoxic T lymphocyte (CTL), naïve CD8+, T helper 1 (Th1), and regulatory T (Treg) cells (right side of figure). The carcinogenic effects of asbestos fibers are shown on the left side, and normal mesothelial cells are gradually transformed toward malignant mesothelioma cells with alteration of tumor suppressor genes such as p16, NF2, and BAP1. Between these two effects, the usual immune surveillance system regarding cancerous cells may be impaired by asbestos exposure
As mentioned at the beginning of this chapter, the carcinogenic actions of asbestos fibers are attributed to (1) oxygen stress, (2) chromosome tangling, and (3) absorption of other carcinogens in the lung [16–20]. Due to these or other mechanisms, mesothelial cells may tend to change their cellular and molecular characteristics toward an abnormal and transformed cell type. For example, p16 cyclin-dependent kinase inhibitor, NF2, neurofibromatosis type 2, BAP1, and breast cancer susceptibility gene 1 (BRCA1 )-associated protein-1 (ubiquitin carboxy-terminal hydrolase) are the typical altered tumor suppressor genes in MM [44–48]. However, many of these transforming cells are usually monitored by immune surveillance and then removed from the body. However, asbestos-exposed individuals may possess an impaired immune surveillance system as described in this chapter, and this impairment may result in MM and other cancers in these individuals after a long latent period [49–53].
Future investigations aimed at neutralizing the immune surveillance system in the asbestos-exposed population through physiologically active substances in foods, plants, and other materials are necessary in order to prevent the occurrence of cancerous diseases in asbestos-exposed individuals.
Acknowledgments
The authors thank Ms. Minako Katoh, Naomi Miyahara, Satomi Hatada, Keiko Yamashita, Keiko Kimura, Tomoko Sueishi, and Misao Kuroki for their technical assistance. All the experimental findings performed in the Department of Hygiene, Kawasaki Medical School, were supported by the Special Coordination Fund for Promoting Science and Technology grant H18-1-3-3-1; JSPS KAKENHI grants 17790375, 19790431, 20890270, 22790550, 23790679, 24590770, and 25860470; Kawasaki Medical School Project grants 29-403, 19-407 M, 20-402O, 20411I, 32-107, 21-401, 22A29, 22B1, 23P3, 23B66, 24B39, and 25B41; the Kawasaki Foundation for Medical Science and Medical Welfare (2007 and 2009); and the Ryobi Teien Memorial Foundation (2009 and 2010).
References
1.
Roggli VL, Coin P. Mineralogy of asbestos. In: Roggi VL, Oury TD, Sporn TA, editors. Pathology of asbestos-associated diseases. New York: Springer; 2004. p. 1–16.CrossRef
2.
Craighead JE, Gibbs A, Pooley F. Mineralogy of asbestos. In: Craighead JE, Gibbs AR, editors. Asbestos and its diseases. New York: Oxford University Press; 2008. p. 23–38.CrossRef
3.
Henderson DW, Leigh J. The history of asbestos utilization and recognition of asbestos-induced diseases. In: Dodson RF, Hammar SO, editors. Asbestos. Risk assessment, epidemiology, and health effects. 2nd ed. Boca Raton: CRC Press; 2011. p. 1–22.CrossRef
4.
Kohyama N, Shinohara Y, Suzuki Y. Mineral phases and some reexamined characteristics of the International Union Against Cancer standard asbestos samples. Am J Ind Med. 1996;30:515–28.PubMed
6.
IARC monograph. A review of human carcinogens: arsenic, metals, fibres, and dusts (Iarc Monographs on the Evaluation of the Carcinogenic Risks to Humans). Geneva: World Health Organization; 2012.
7.
Le GV, Takahashi K, Park EK, Delgermaa V, Oak C, Qureshi AM, Aljunid SM. Asbestos use and asbestos-related diseases in Asia: past, present and future. Respirology. 2011;16:767–75. doi:10.1111/j.1440-1843.2011.01975.x.CrossRefPubMed
8.
Kameda T, Takahashi K, Kim R, Jiang Y, Movahed M, Park EK, Rantanen J. Asbestos: use, bans and disease burden in Europe. Bull World Health Organ. 2014;92:790–7. doi:10.2471/BLT.13.132118.CrossRefPubMedPubMedCentral
9.
O’Bryne K, Rusch V, editors. Malignant pleural mesothelioma. New York: Oxford University Press; 2006.
10.
Hammar SP. Asbestos and mesothelioma. In: Dodson RF, Hammar SO, editors. Asbestos. Risk assessment, epidemiology, and health effects. 2nd ed. Boca Raton: CRC Press; 2011. p. 307–418.CrossRef
11.
Gibbs AR, Craighead JE. Malignant diseases of the pleura, peritoneum, and other serosal surface. In: Craighead JE, Gibbs AR, editors. Asbestos and its diseases. New York: Oxford University Press; 2008. p. 190–229.CrossRef
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