title: Synergistic protection against hyperoxia-induced lung injury by neutrophils blockade and EC-SOD overexpression.
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).
  
  
  CONCLUSIONS
  Combined strategy of EC-SOD and neutrophil influx blockade may have a therapeutic benefit in protecting the lung against acute hyperoxic injury.
authors: Department of Pediatrics, State University of New York, Downstate MedicalCenter, Brooklyn, New York, NY, USA.
authors: Jae H
authors: JH
authors: Min
authors: Champa N
authors: CN
authors: Codipilly
authors: Sonya
authors: S
authors: Nasim
authors: Edmund J
authors: EJ
authors: Miller
authors: Mohamed N
authors: MN
authors: Ahmed
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018496:Hyperoxia / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D055370:Lung Injury / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D009842:Oligopeptides; C118980:antileukinate; C441642:SOD3 protein, human; D013482:Superoxide Dismutase