CXCR4 blockade attenuates hyperoxia-induced lung injury in neonatal rats

Shelley Drummond, Shalini Ramachandran, Eneida Torres, Jian Huang, Dorothy Hehre, Cleide Suguihara, Karen C. Young

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background: Lung inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Stromal-derived factor-1 (SDF-1) and its receptor chemokine receptor 4 (CXCR4) modulate the inflammatory response. It is not known if antagonism of CXCR4 alleviates lung inflammation in neonatal hyperoxia-induced lung injury. Objective: We aimed to determine whether CXCR4 antagonism would attenuate lung injury in rodents with experimental BPD by decreasing pulmonary inflammation. Methods: Newborn rats exposed to normoxia (room air, RA) or hyperoxia (FiO<inf>2</inf> = 0.9) from postnatal day 2 (P2) to P16 were randomized to receive the CXCR4 antagonist, AMD3100 or placebo (PL) from P5 to P15. Lung alveolarization, angiogenesis and inflammation were evaluated at P16. Results: Compared to the RA pups, hyperoxic PL pups had a decrease in alveolarization, reduced lung vascular density and increased lung inflammation. In contrast, AMD3100-treated hyperoxic pups had improved alveolarization and increased angiogenesis. This improvement in lung structure was accompanied by a decrease in the macrophage and neutrophil counts in the bronchoalveolar lavage fluid and reduced lung myeloperoxidase activity. Conclusion: CXCR4 antagonism decreases lung inflammation and improves alveolar and vascular structure in neonatal rats with experimental BPD. These findings suggest a novel therapeutic strategy to alleviate lung injury in preterm infants with BPD.

Original languageEnglish (US)
Pages (from-to)304-311
Number of pages8
JournalNeonatology
Volume107
Issue number4
DOIs
StatePublished - Jun 9 2015

Keywords

  • Angiogenesis
  • Bronchopulmonary dysplasia
  • CXCR4 blockade
  • Hyperoxia

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health

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    Drummond, S., Ramachandran, S., Torres, E., Huang, J., Hehre, D., Suguihara, C., & Young, K. C. (2015). CXCR4 blockade attenuates hyperoxia-induced lung injury in neonatal rats. Neonatology, 107(4), 304-311. https://doi.org/10.1159/000371835