Two-dimensional analysis of elements and mononuclear cells in hard metal lung disease.
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.
Moriyama
Hiroshi
H
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Japan.
Kobayashi
Masayoshi
M
Takada
Toshinori
T
Shimizu
Takashi
T
Terada
Masaki
M
Narita
Jun-Ichi
J
Maruyama
Michio
M
Watanabe
Kouichi
K
Suzuki
Eiichi
E
Gejyo
Fumitake
F
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
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