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-alpha and transforming growth factor (TGF)-beta1; TGF-beta 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.
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-alpha and transforming growth factor (TGF)-beta1; TGF-beta 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.
Authors: K Arsalane; C M Dubois; T Muanza; R Bégin; F Boudreau; C Asselin; A M Cantin Journal: Am J Respir Cell Mol Biol Date: 1997-11 Impact factor: 6.914
Authors: Kevin R Flaherty; Thomas V Colby; William D Travis; Galen B Toews; Jeanette Mumford; Susan Murray; Victor J Thannickal; Ella A Kazerooni; Barry H Gross; Joseph P Lynch; Fernando J Martinez Journal: Am J Respir Crit Care Med Date: 2003-02-20 Impact factor: 21.405
Authors: K Kuwano; N Nakashima; I Inoshima; N Hagimoto; M Fujita; M Yoshimi; T Maeyama; N Hamada; K Watanabe; N Hara Journal: Eur Respir J Date: 2003-02 Impact factor: 16.671
Authors: B Loenders; E Van Mechelen; S Nicolaï; N Buyssens; N Van Osselaer; P G Jorens; J Willems; A G Herman; H Slegers Journal: Free Radic Biol Med Date: 1998-05 Impact factor: 7.376
Authors: Melissa L T Teoh-Fitzgerald; Matthew P Fitzgerald; Taylor J Jensen; Bernard W Futscher; Frederick E Domann Journal: Mol Cancer Res Date: 2011-11-07 Impact factor: 5.852
Authors: Vincent F Fiore; Megan C Lofton; Susanne Roser-Page; Stephen C Yang; Jesse Roman; Niren Murthy; Thomas H Barker Journal: Biomaterials Date: 2009-10-20 Impact factor: 12.479
Authors: Carmen Veith; Agnes W Boots; Musa Idris; Frederik-Jan van Schooten; Albert van der Vliet Journal: Antioxid Redox Signal Date: 2019-04-05 Impact factor: 8.401
Authors: Angela K Tollefson; Rebecca E Oberley-Deegan; Kiel T Butterfield; Michael E Nicks; Michael R Weaver; Linda K Remigio; Jessica Decsesznak; H W Chu; Donna L Bratton; David W Riches; Russell P Bowler Journal: Free Radic Biol Med Date: 2010-09-29 Impact factor: 7.376