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Extracellular superoxide dismutase has a highly specific localization in idiopathic pulmonary fibrosis/usual interstitial pneumonia

Aims : Recent studies suggest the importance of oxidant stress in the progression of pulmonary fibrosis. The aim of this study was to investigate extracellular superoxide dismutase (ECSOD), the major antioxidant enzyme of the extracellular matrix of human lung, in biopsy‐proven idiopathic pulmonary...

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Bibliographic Details
Published in:Histopathology 2006-07, Vol.49 (1), p.66-74
Main Authors: Kinnula, V L, Hodgson, U A, Lakari, E K, Tan, R J, Sormunen, R T, Soini, Y M, Kakko, S J, Laitinen, T H, Oury, T D, Pääkkö, P K
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Language:English
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Summary:Aims : Recent studies suggest the importance of oxidant stress in the progression of pulmonary fibrosis. The aim of this study was to investigate extracellular superoxide dismutase (ECSOD), the major antioxidant enzyme of the extracellular matrix of human lung, in biopsy‐proven idiopathic pulmonary fibrosis (IPF) related to usual interstitial pneumonia (UIP). Methods and results : Fibrotic areas and fibroblastic foci in UIP lungs were notable for absence of ECSOD by immunohistochemistry. Western blotting showed significantly lowered immunoreactivity of ECSOD in fibrotic compared with non‐fibrotic areas of the diseased lung. The only cell type that showed intense ECSOD positivity in UIP was the interstitial mast cell. In order to investigate the mechanism for ECSOD depletion in fibrotic areas, alveolar epithelial cells were exposed to tumour necrosis factor‐α and transforming growth factor (TGF)‐β1; TGF‐β suggested a trend towards decreased synthesis. Patients with UIP were also assessed to determine whether this disease is associated with a naturally occurring mutation in ECSOD (Arg213Gly) which leads to a loss of tissue binding of ECSOD. No significant differences could be found in the allele or genotype frequencies of this polymorphism between 63 UIP patients and 61 control subjects. Conclusion : Overall, consistent with several other antioxidant enzymes, ECSOD is very low in fibrotic areas of UIP, which may further increase the oxidant burden in this disease.
ISSN:0309-0167
1365-2559
DOI:10.1111/j.1365-2559.2006.02470.x