Synthesis and anti-inflammatory activity of a chimeric recombinant superoxide dismutase: SOD2/3

Am J Physiol Lung Cell Mol Physiol. 2003 Jun;284(6):L917-25. doi: 10.1152/ajplung.00374.2002. Epub 2003 Jan 10.


External surfaces of cells are normally protected by extracellular superoxide dismutase, SOD3, which binds to polyanions such as heparan sulfate. We constructed a fusion gene encoding a chimeric SOD consisting of the mature human mitochondrial SOD2 plus the COOH-terminal 26-amino acid heparin-binding "tail" from SOD3. This tail is responsible for the enzyme's affinity for endothelial surfaces. The fusion gene was expressed in Escherichia coli, and the fully active enzyme SOD2/3 was purified. Although native SOD2 has no affinity for heparin, SOD2/3 binds to a heparin-agarose column. In a rat model of acute lung injury induced by intratracheal instillation of IL-1, SOD2/3, SOD2, and denatured SOD2/3 showed 92%, 13.8%, and 0% reduction of lung leak, respectively. Only SOD2/3 prevented neutrophil accumulation. In the carrageenan-induced foot edema model in the rat, SOD2/3 reduced edema by 62% (P < 0.003) at a dose in which native SOD2 produced no significant effect. Thus SOD2/3 appears to have properties as a therapeutic anti-inflammatory agent that are greatly superior to other available forms of the enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Carrageenan
  • Disease Models, Animal
  • Edema / chemically induced
  • Edema / drug therapy
  • Extremities
  • Gene Expression Regulation, Enzymologic
  • Heparin / metabolism
  • Humans
  • Interleukin-1 / pharmacology
  • Male
  • Molecular Sequence Data
  • Neutrophils / immunology
  • Oxidative Stress / immunology
  • Plasmids
  • Pneumonia / drug therapy*
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / immunology*
  • Superoxide Dismutase / pharmacology


  • Interleukin-1
  • Recombinant Fusion Proteins
  • Carrageenan
  • Heparin
  • SOD3 protein, human
  • Sod3 protein, rat
  • Superoxide Dismutase
  • superoxide dismutase 2