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

Antioxid Redox Signal. 2008 Feb;10(2):261-8. doi: 10.1089/ars.2007.1906.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asbestosis / prevention & control
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / physiology
  • Disease Models, Animal
  • Extracellular Matrix / physiology*
  • Heparin / metabolism
  • Heparitin Sulfate / metabolism*
  • Humans
  • Lung / drug effects
  • Lung / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Pulmonary Fibrosis / prevention & control
  • Superoxide Dismutase / pharmacology*
  • Superoxides / metabolism


  • Superoxides
  • Heparin
  • Heparitin Sulfate
  • Superoxide Dismutase