Synergistic protection against hyperoxia-induced lung injury by neutrophils blockade and EC-SOD overexpression

Respir Res. 2012 Jul 20;13(1):58. doi: 10.1186/1465-9921-13-58.

Abstract

Background: Oxygen may damage the lung directly via generation of reactive oxygen species (ROS) or indirectly via the recruitment of inflammatory cells, especially neutrophils. Overexpression of extracellular superoxide dismutase (EC-SOD) has been shown to protect the lung against hyperoxia in the newborn mouse model. The CXC-chemokine receptor antagonist (Antileukinate) successfully inhibits neutrophil influx into the lung following a variety of pulmonary insults. In this study, we tested the hypothesis that the combined strategy of overexpression of EC-SOD and inhibiting neutrophil influx would reduce the inflammatory response and oxidative stress in the lung after acute hyperoxic exposure more efficiently than either single intervention.

Methods: Neonate transgenic (Tg) (with an extra copy of hEC-SOD) and wild type (WT) were exposed to acute hyperoxia (95% FiO2 for 7 days) and compared to matched room air groups. Inflammatory markers (myeloperoxidase, albumin, number of inflammatory cells), oxidative markers (8-isoprostane, ratio of reduced/oxidized glutathione), and histopathology were examined in groups exposed to room air or hyperoxia. During the exposure, some mice received a daily intraperitoneal injection of Antileukinate.

Results: Antileukinate-treated Tg mice had significantly decreased pulmonary inflammation and oxidative stress compared to Antileukinate-treated WT mice (p < 0.05) or Antileukinate-non-treated Tg mice (p < 0.05).

Conclusion: Combined strategy of EC-SOD and neutrophil influx blockade may have a therapeutic benefit in protecting the lung against acute hyperoxic injury.

MeSH terms

  • Animals
  • Animals, Newborn
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hyperoxia / enzymology*
  • Hyperoxia / genetics
  • Hyperoxia / prevention & control
  • Lung Injury / enzymology*
  • Lung Injury / genetics
  • Lung Injury / prevention & control
  • Mice
  • Mice, Transgenic
  • Neutrophils / drug effects
  • Neutrophils / enzymology*
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Superoxide Dismutase / biosynthesis*
  • Superoxide Dismutase / genetics

Substances

  • Oligopeptides
  • antileukinate
  • SOD3 protein, human
  • Superoxide Dismutase