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

Respiratory Research

Mohamed N Ahmed³  Edmund J Miller¹  Sonya Nasim⁴  Champa N Codipilly⁴  Jae H Min² 

[1] Department of Medicine, North Shore University Hospital, Manhasset, NY, 11030, USA;Department of Pediatrics, State University of New York, Downstate Medical Center, Brooklyn, New York, NY, USA;Department of Pediatrics, Division of Neonatal-Perinatal medicine, Cohen Children, NS-LIJ Hospitals, 300 Community Dr.Manhasset, Manhasset, NY, 11725, USA;Center for Heart and Lung Research, Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA

关键词: Lung injury;    Hyperoxia;    CXC-chemokine receptor;    Antileukinate;    Extracellular superoxide dismutase;   

Others  :  1146827
DOI  :  10.1186/1465-9921-13-58

 received in 2012-03-20, accepted in 2012-07-20,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 MIN et al.; licensee BioMed Central Ltd.

【 图 表 】

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