Intensive Care Medicine

, 37:1680

Overexpression of pulmonary extracellular superoxide dismutase attenuates endotoxin-induced acute lung injury

  • Patrick Hassett
  • Gerard F. Curley
  • Maya Contreras
  • Claire Masterson
  • Brendan D. Higgins
  • Timothy O’Brien
  • James Devaney
  • Daniel O’Toole
  • John G. Laffey
Experimental

DOI: 10.1007/s00134-011-2309-y

Cite this article as:
Hassett, P., Curley, G.F., Contreras, M. et al. Intensive Care Med (2011) 37: 1680. doi:10.1007/s00134-011-2309-y

Abstract

Purpose

Superoxide is produced by activated neutrophils during the inflammatory response to stimuli such as endotoxin, can directly or indirectly injure host cells, and has been implicated in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We wished to determine the potential for pulmonary overexpression of the extracellular isoform of superoxide dismutase (EC-SOD) to reduce the severity of endotoxin-induced lung injury.

Methods

Animals were randomly allocated to undergo intratracheal instillation of (1) surfactant alone (vehicle); (2) adeno-associated virus (AAV) vectors containing a null transgene (AAV-null); and (3) adeno-associated virus vectors containing the EC-SOD transgene (AAV-EC-SOD) and endotoxin was subsequently administered intratracheally. Two additional groups were randomized to receive (1) vehicle or (2) AAV-EC-SOD, and to undergo sham (vehicle) injury. The severity of the lung injury was assessed in all animals 24 h later.

Results

Endotoxin produced a severe lung injury compared to sham injury. The AAV vector encoding EC-SOD increased lung EC-SOD concentrations, and enhanced the antioxidant capacity of the lung. EC-SOD overexpression decreased the severity of endotoxin-induced ALI, reducing the decrement in systemic oxygenation and lung compliance, decreasing lung permeability and decreasing histologic injury. EC-SOD attenuated pulmonary inflammation, decreased bronchoalveolar lavage neutrophil counts, and reduced interleukin-6 and CINC-1 concentrations. The AAV vector itself did not contribute to inflammation or to lung injury.

Conclusions

Pulmonary overexpression of EC-SOD protects the lung against endotoxin-induced ALI.

Keywords

Acute lung injurySuperoxide dismutaseRatAcute respiratory distress syndromeEndotoxinSepsis

Supplementary material

134_2011_2309_MOESM1_ESM.doc (96 kb)
Supplementary material 1 (DOC 97 kb)
134_2011_2309_MOESM2_ESM.tif (1 mb)
Supplementary material 2 (TIFF 1062 kb)
134_2011_2309_MOESM3_ESM.tif (3.1 mb)
Supplementary material 3 (TIFF 3162 kb)

Copyright information

© Copyright jointly held by Springer and ESICM 2011

Authors and Affiliations

  • Patrick Hassett
    • 1
    • 2
  • Gerard F. Curley
    • 1
    • 2
  • Maya Contreras
    • 1
    • 2
  • Claire Masterson
    • 1
    • 2
  • Brendan D. Higgins
    • 1
    • 2
  • Timothy O’Brien
    • 3
  • James Devaney
    • 1
    • 2
    • 3
  • Daniel O’Toole
    • 1
    • 2
    • 3
  • John G. Laffey
    • 1
    • 2
    • 3
  1. 1.Anaesthesia, School of Medicine, Clinical Sciences InstituteNational University of IrelandGalwayIreland
  2. 2.Lung Biology Group, National Centre for Biomedical Engineering SciencesNational University of IrelandGalwayIreland
  3. 3.Regenerative Medicine InstituteNational University of IrelandGalwayIreland