**Immunological Risks Caused by Fibrous and Particulate Substances**

Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Shoko Yamamoto, Tamayo Hatayama, Kei Yoshitome, Hiroaki Hayashi, Megumi Maeda and Takemi Otsuki

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/62749

#### **Abstract**

The immunological risks caused by fibrous and particulate substances, especially the effects caused by asbestos fibers and silica particles, are discussed in this chapter. Patients with silicosis often suffer from autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, and antineutrophil cytoplasmic antibody–related vasculitis. Silica particles, SiO2, may influence directly various immune cells resulting in the production of many autoantibodies and imbalance between responder and regulatory T cells. The core chemical content of asbestos fibers is Si and O, although the physical feature is different. Considering the complications in asbestos-exposed patients, malignant tumors, such as lung cancer and malignant mesothelioma, are the most important. To think about these situations, asbestos fibers may cause the reduction of antitumor immunity. The experimental findings and measurements of various immunological parameters in silicosis patients, as well as asbestos-exposed population, such as patients with pleural plaque and mesothelioma, are demonstrated and discussed in this chapter.

**Keywords:** asbestos, silica, autoimmune diseases, antitumor immunity, regulatory T cell

### **1. Introduction**

Regarding environmental factors that cause health risks, exposure to fibrous and particulate substances, such as asbestos fibers and silica particles, represent classic examples, and the

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

investigation of other materials that lead to health impairment following exposure is ongoing [1–10]. In addition to pulmonary effects, such as fibrosis, chronic inflammations, and cancers, such as lung malignancies and pleural mesothelioma, in asbestos-exposed patients, there may be certain effects on immunological cells [11–16]. Among people who have been exposed to asbestos fibers or silica particles, people exposed to silica and have developed silicosis often suffer from complicated autoimmune diseases, such as rheumatoid arthritis, systemic sclero‐ sis, and antineutrophil cytoplasmic antigen (ANCA)–related vasculitis [17–20]. The core chemical components of asbestos fibers are Si and O2, and although the physical makeup of fibrous and particulate matter differs, asbestos fibers may affect the immune system. Therefore, we have been investigating the immunological effects of silica and asbestos [11–16].

Regarding silica particles, the mechanism of silica-induced dysregulation of autoimmunity is thought to involve silica acting as an adjuvant [21–24]. However, silica particles may also act by directly stimulating on circulating peripheral immune cells, which cause certain alterations in the cellular or molecular functions of these cells, since silica particles may remain in pulmonary lesions and lymph nodes after inhalation [11–16]. Since these direct effects may change the characteristics of immune cells and consequently facilitate the dysregulation of immune tolerance, clarification of these cellular and molecular mechanisms may be useful in the prevention of immune disorders that occur in silicosis patients (SIL), in addition to contributing toward an understanding of the etiology of various autoimmune diseases.

We have been focusing on the immunological effects of silica using human peripheral blood immune cells derived from healthy donors (HD) and SIL [11–14]. We will summarize our findings which indicate that silica is an environmental immune stimulator, and chronic activation of immune cells induced by recurrent and chronic exposure to silica causes an imbalance in the regulation of T cell responses.

Regarding asbestos fibers, asbestos-related cancers, such as malignant mesothelioma (MM) and lung cancer, have been a major global concern in Japan [25–29]. Given the conflict that has arisen due to economic considerations and the medical evidence, there is a confusion con‐ cerning the pathological mechanisms of asbestos-induced cancers, and in particular, an uncertainty concerning the dangers of iron-absent chrysotile (white) asbestos compared with iron-present crocidolite (blue) and amosite (brown) asbestos [30–33]. However, regarding the poor prognosis of MM, novel medical approaches to investigate the biological effects of asbestos and pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect early stages of MM, should be implemented to assist in the development of improved prevention strategies and cure of asbestos-related malignancies [34–36]. From this standpoint, our group has been investigating the immunological effects of asbestos with respect to the reduction of tumor immunity [11, 12, 15, 16]. In this chapter, cellular and molecular approaches to clarify the immunological effects of asbestos are described, and all findings indicate that a reduction of tumor immunity is caused by asbestos exposure and is involved in asbestos-induced cancers. In addition to confirming the well-known biological effects of asbestos, these investigations provide a basis for the development of a novel procedure for the early detection of previous asbestos exposure, mesothelioma and the chemoprevention of asbestos-related cancers.

As shown in **Figure 1**, both silica particles and asbestos fibers cause pulmonary fibrosis known as pneumoconiosis, silicosis, and asbestosis. Additionally, both can affect various immune cells, such as B cells, CD4 T helper (Th1), regulatory T (Treg), cytotoxic T lymphocyte (CTL), natural killer (NK) cells, and other immune cells [11, 12, 15, 16].

**Figure 1.** Schematic representation of immunological risks caused by exposure to silica particles and asbestos fibers. The immunological risks induced crucial complications, such as autoimmune diseases, in silicosis patients, as well as malignant tumors, such as lung cancer and malignant mesothelioma, in asbestos-exposed populations.

In this chapter, the immunological effects on various immune cells caused by silica particles and asbestos fibers as investigated in our laboratory will be presented and discussed with respect to the detection of immunological risks of particulate and fibrous environmental factors [11–16]. These summarized findings may be helpful in the development of future risk man‐ agement strategies, including cases related to newly developed fibrous and particulate matter, such as nanoparticles and nanotubes.
