Extracellular superoxide dismutase protects against matrix degradation of heparan sulfate in the lung.


Journal Article

Asbestosis is a form of interstitial lung disease caused by the inhalation of asbestos fibers, leading to inflammation and pulmonary fibrosis. Inflammation and oxidant/antioxidant imbalances are known to contribute to the disease pathogenesis. Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that has been shown to protect the lung from oxidant-mediated damage, inflammation, and interstitial fibrosis. Extracellular matrix (ECM) components, such as collagen and glycosaminoglycans, are known to be sensitive to oxidative fragmentation. Heparan sulfate, a glycosaminoglycan, is highly abundant in the ECM and tightly binds EC-SOD. We investigated the protective role of EC-SOD by evaluating the interaction of EC-SOD with heparan sulfate in the presence of reactive oxygen species (ROS). We found that ROS-induced heparin and heparan sulfate fragments induced neutrophil chemotaxis across a modified Boyden chamber, which was inhibited by the presence of EC-SOD by scavenging oxygen radicals. Chemotaxis in response to oxidatively fragmented heparin was mediated by Toll-like receptor-4. In vivo, bronchoalveolar lavage fluid from EC-SOD knockout mice at 1, 14, and 28 days after asbestos exposure showed increased heparan sulfate shedding from the lung parenchyma. We demonstrate that one mechanism through which EC-SOD inhibits lung inflammation and fibrosis in asbestosis is by protecting heparin/heparan sulfate from oxidative fragmentation.

Full Text

Cited Authors

  • Kliment, CR; Tobolewski, JM; Manni, ML; Tan, RJ; Enghild, J; Oury, TD

Published Date

  • February 2008

Published In

Volume / Issue

  • 10 / 2

Start / End Page

  • 261 - 268

PubMed ID

  • 17961072

Pubmed Central ID

  • 17961072

Electronic International Standard Serial Number (EISSN)

  • 1557-7716

International Standard Serial Number (ISSN)

  • 1523-0864

Digital Object Identifier (DOI)

  • 10.1089/ars.2007.1906


  • eng