CXCR2 Is Critical to Hyperoxia-Induced Lung Injury

  • Richard D Sue
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • John A Belperio
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • Marie D Burdick
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • Lynne A Murray
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • Ying Ying Xue
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • Maria C Dy
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • Jeffery J Kwon
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • Michael P Keane
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095
  • Robert M Strieter
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California , Los Angeles, CA 90095

書誌事項

公開日
2004-03
権利情報
  • https://academic.oup.com/pages/standard-publication-reuse-rights
DOI
  • 10.4049/jimmunol.172.6.3860
公開者
Oxford University Press (OUP)

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説明

<jats:title>Abstract</jats:title> <jats:p>Hyperoxia-induced lung injury is characterized by infiltration of activated neutrophils in conjunction with endothelial and epithelial cell injury, followed by fibrogenesis. Specific mechanisms recruiting neutrophils to the lung during hyperoxia-induced lung injury have not been fully elucidated. Because CXCL1 and CXCL2/3, acting through CXCR2, are potent neutrophil chemoattractants, we investigated their role in mediating hyperoxia-induced lung injury. Under variable concentrations of oxygen, murine survival during hyperoxia-induced lung injury was dose dependent. Eighty percent oxygen was associated with 50% mortality at 6 days, while greater oxygen concentrations were more lethal. Using 80% oxygen, we found that lungs harvested at day 6 demonstrated markedly increased neutrophil sequestration and lung injury. Expression of CXCR2 ligands paralleled neutrophil recruitment to the lung and CXCR2 mRNA expression. Inhibition of CXC chemokine ligands/CXCR2 interaction using CXCR2−/− mice exposed to hyperoxia significantly reduced neutrophil sequestration and lung injury, and led to a significant survival advantage as compared with CXCR2+/+ mice. These findings demonstrate that CXC chemokine ligand/CXCR2 biological axis is critical during the pathogenesis of hyperoxia-induced lung injury.</jats:p>

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