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

Jae H. Min, Champa N. Codipilly, Sonya Nasim, Edmund J. Miller, Mohamed N. Ahmed

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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% FiO 2 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.

Original languageEnglish (US)
Article number58
JournalRespiratory Research
Volume13
DOIs
StatePublished - Jul 20 2012
Externally publishedYes

Keywords

  • Antileukinate
  • CXC-chemokine receptor
  • Extracellular superoxide dismutase
  • Hyperoxia
  • Lung injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint

Dive into the research topics of 'Synergistic protection against hyperoxia-induced lung injury by neutrophils blockade and EC-SOD overexpression'. Together they form a unique fingerprint.

Cite this