title: Two-dimensional analysis of elements and mononuclear cells in hard metal lung disease.
abstract: BACKGROUND
  Hard metal lung disease is caused by exposure to hard metal, a synthetic compound that combines tungsten carbide with cobalt as well as a number of other metals. Interstitial lung disease caused by hard metal is uniquely characterized by giant cell interstitial pneumonia. The pathogenesis of hard metal lung disease is unclear.
  
  
  OBJECTIVE
  To elucidate the distribution of inhaled hard metal and reactive inflammatory cells in biopsy lung tissue from patients with hard metal lung disease.
  
  
  METHODS
  Seventeen patients with interstitial lung disease in which tungsten was detected and five control subjects were studied. Detection and mapping of elements were performed with an electron probe microanalyzer equipped with a wavelength dispersive spectrometer. We immunohistochemically stained mononuclear cells, in tissue samples available from five patients, with anti-human CD4, CD8, CD20, CD68, and CD163 antibodies, and compared the distribution of positive cells with hard metal elements.
  
  
  RESULTS
  Thirteen of 17 patients were pathologically diagnosed as having giant cell interstitial pneumonia. Tungsten and cobalt were accumulated in the centrilobular fibrotic lesions, but were never found in the control lungs. CD8+ lymphocytes and CD163+ monocyte-macrophages were distributed predominantly in centrilobular fibrotic lesions around the hard metal elements. CD163+ colocalized with tungsten. Small numbers of CD8+ and CD163+ cells were also immunohistochemically shown in peribronchiolar areas and alveolar walls.
  
  
  CONCLUSIONS
  Macrophages may phagocytose inhaled tungsten via CD163 and play an important role in forming the fibrotic lesion of hard metal lung disease with cytotoxic T lymphocytes.
authors.affiliation: Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriyama
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Takada
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Masaki
authors.initials: M
authors.lastname: Terada
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Narita
authors.forename: Michio
authors.initials: M
authors.lastname: Maruyama
authors.forename: Kouichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Eiichi
authors.initials: E
authors.lastname: Suzuki
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
mesh_terms: D000328:Adult; D000497:Alloys / Q000009:adverse effects; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D003035:Cobalt / Q000009:adverse effects / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015743:Giant Cells, Foreign-Body / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017563:Lung Diseases, Interstitial / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010587:Phagocytosis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014414:Tungsten / Q000009:adverse effects / Q000276:immunology*; D017973:Tungsten Compounds / Q000009:adverse effects / Q000276:immunology; D000098902:CD163 Antigen
chemical_list: D000497:Alloys; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D017973:Tungsten Compounds; C080121:hard metal; C002802:tungsten carbide; D003035:Cobalt; D014414:Tungsten