title: Co-localization of iron binding on silica with p62/sequestosome1 (SQSTM1) in lung granulomas of mice with acute silicosis.
abstract: The cellular mechanisms involved in the development of silicosis have not been fully elucidated. This study aimed to examine influence of silica-induced lung injury on autophagy. Suspensions of crystalline silica particles were administered transnasally to C57BL/6j mice. Immunohistochemical examination for Fas and p62 protein expression was performed using lung tissue specimens. Two-dimensional and quantitative analysis of silica deposits in the lungs were performed in situ using lung tissue sections by an in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis system, which was based on irrradiation of specimens with a proton ion microbeam. Quantitative analysis showed a significant increase of iron levels on silica particles (assessed as the ratio of Fe relative to Si) on day 56 compared with day 7 (p<0.05). Fas and p62 were expressed by histiocytes in granulomas on day 7, and the expressions persisted for day 56. Fas- and p62-expressing histiocytes were co-localized in granulomas with silica particles that showed an increase of iron levels on silica particles in mouse lungs. Iron complexed with silica induces apoptosis, and may lead to dysregulations of autophagy in histiocytes of granulomas, and these mechanisms may contribute to granuloma development and progression in silicosis.
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Tochigi 321-0293, Japan ; Department of Respiratory Medicine, Maebashi Red Cross Hospital, 3-21-36 Asahi-cho, Maebashi-shi, Tochigi 371-0014, Japan ; Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi-shi, Gunma 371-8511, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Gunma University School of Health Sciences, 3-39-22 Showa-machi, Maebashi-shi, Gunma 371-8514, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Dobashi
authors.affiliation: Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagase
authors.affiliation: Department of Respiratory Diseases, National Hospital Organization Tokyo National Hospital, Tokyo, 3-1-1 Takeoka, Kiyose-shi, Tokyo 204-8585, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi-shi, Gunma 371-8511, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sano
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi-shi, Gunma 371-8511, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Matsuzaki
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Tochigi 321-0293, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, 1233 Watanuki-machi, Takasaki-shi, Gunma 370-1292, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, 1233 Watanuki-machi, Takasaki-shi, Gunma 370-1292, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Koka
authors.affiliation: Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, 1233 Watanuki-machi, Takasaki-shi, Gunma 370-1292, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, 1233 Watanuki-machi, Takasaki-shi, Gunma 370-1292, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Ohkubo
authors.affiliation: Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, 1233 Watanuki-machi, Takasaki-shi, Gunma 370-1292, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, 1233 Watanuki-machi, Takasaki-shi, Gunma 370-1292, Japan.
authors.forename: Tomihiro
authors.initials: T
authors.lastname: Kamiya
keywords: Fas; apoptosis; autophagy; p62; silicosis
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