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Extracellular superoxide dismutase has a highly specific localization in idiopathic pulmonary fibrosis/usual interstitial pneumonia
Author(s) -
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
Publication year - 2006
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2006.02470.x
Subject(s) - idiopathic pulmonary fibrosis , usual interstitial pneumonia , pulmonary fibrosis , pathology , fibrosis , lung , transforming growth factor , extracellular matrix , interstitial lung disease , superoxide dismutase , biology , medicine , oxidative stress , microbiology and biotechnology
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)‐β 1 ; 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 (Arg 213 Gly) 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.