title: Elemental analysis of lung tissue particles and intracellular iron content of alveolar macrophages in pulmonary alveolar proteinosis.
abstract: BACKGROUND
  Pulmonary alveolar proteinosis (PAP) is a rare disease occurred by idiopathic (autoimmune) or secondary to particle inhalation. The in-air microparticle induced X-ray emission (in-air micro-PIXE) system performs elemental analysis of materials by irradiation with a proton microbeam, and allows visualization of the spatial distribution and quantitation of various elements with very low background noise. The aim of this study was to assess the secondary PAP due to inhalation of harmful particles by employing in-air micro-PIXE analysis for particles and intracellular iron in parafin-embedded lung tissue specimens obtained from a PAP patient comparing with normal lung tissue from a non-PAP patient. The iron inside alveolar macrophages was stained with Berlin blue, and its distribution was compared with that on micro-PIXE images.
  
  
  RESULTS
  The elements composing particles and their locations in the PAP specimens could be identified by in-air micro-PIXE analysis, with magnesium (Mg), aluminum (Al), silicon (Si), phosphorus (P), sulfur (S), scandium (Sc), potassium (K), calcium (Ca), titanium (Ti), chromium (Cr), copper (Cu), manganase (Mn), iron (Fe), and zinc (Zn) being detected. Si was the major component of the particles. Serial sections stained by Berlin blue revealed accumulation of sideromacrophages that had phagocytosed the particles. The intracellular iron content of alveolar macrophage from the surfactant-rich area in PAP was higher than normal lung tissue in control lung by both in-air micro-PIXE analysis and Berlin blue staining.
  
  
  CONCLUSIONS
  The present study demonstrated the efficacy of in-air micro-PIXE for analyzing the distribution and composition of lung particles. The intracellular iron content of single cells was determined by simultaneous two-dimensional and elemental analysis of paraffin-embedded lung tissue sections. The results suggest that secondary PAP is associated with exposure to inhaled particles and accumulation of iron in alveolar macrophages.
authors: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan. yasuos@med.gunma-u.ac.jp
authors: Yasuo
authors: Y
authors: Shimizu
authors: Shinichi
authors: S
authors: Matsuzaki
authors: Kunio
authors: K
authors: Dobashi
authors: Noriko
authors: N
authors: Yanagitani
authors: Takahiro
authors: T
authors: Satoh
authors: Masashi
authors: M
authors: Koka
authors: Akihito
authors: A
authors: Yokoyama
authors: Takeru
authors: T
authors: Ohkubo
authors: Yasuyuki
authors: Y
authors: Ishii
authors: Tomihiro
authors: T
authors: Kamiya
authors: Masatomo
authors: M
authors: Mori
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D007501:Iron / Q000032:analysis*; D008168:Lung / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000737:chemistry*; D008875:Middle Aged; D016612:Paraffin Embedding; D010316:Particle Size; D052638:Particulate Matter / Q000009:adverse effects*; D010587:Phagocytosis; D011649:Pulmonary Alveolar Proteinosis / Q000209:etiology / Q000378:metabolism*; D013052:Spectrometry, X-Ray Emission; D013194:Staining and Labeling
chemical_list: D052638:Particulate Matter; D007501:Iron