期刊
JOURNAL OF IMMUNOLOGY
卷 172, 期 6, 页码 3860-3868出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.172.6.3860
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资金
- NCI NIH HHS [CA87879, P50CA90388] Funding Source: Medline
- NHLBI NIH HHS [HL04493, HL03906, HL66027, P50HL67665] Funding Source: Medline
- CSR NIH HHS [RG-019-B] Funding Source: Medline
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.
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