Co-localization of iron binding on silica with p62/sequestosome1 (SQSTM1) in lung granulomas of mice with acute silicosis

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Author(s)

    • Shimizu Yasuo
    • Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine|Department of Respiratory Medicine, Maebashi Red Cross Hospital|Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine
    • Yokoyama Akihito
    • Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute
    • Ohkubo Takeru
    • Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute
    • Ishii Yasuyuki
    • Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute
    • Kamiya Tomihiro
    • Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute
    • Nagase Hiroyuki
    • Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine
    • Ohta Ken
    • Department of Respiratory Diseases, National Hospital Organization Tokyo National Hospital
    • Sano Takaaki
    • Department of Diagnostic Pathology, Gunma University Graduate School of Medicine
    • Matsuzaki Shinichi
    • Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine
    • Ishii Yoshiki
    • Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine
    • Satoh Takahiro
    • Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute
    • Koka Masashi
    • Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute

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 <i>in situ</i> 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 (<i>p</i><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.

Journal

  • Journal of Clinical Biochemistry and Nutrition

    Journal of Clinical Biochemistry and Nutrition 56(1), 74-83, 2015

    SOCIETY FOR FREE RADICAL RESEARCH JAPAN

Codes

  • NII Article ID (NAID)
    130004704980
  • Text Lang
    ENG
  • ISSN
    0912-0009
  • Data Source
    J-STAGE 
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