title: CXCR4 blockade attenuates hyperoxia-induced lung injury in neonatal rats.
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 (FiO2 = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Fla., USA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Drummond
authors.forename: Shalini
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Eneida
authors.initials: E
authors.lastname: Torres
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hehre
authors.forename: Cleide
authors.initials: C
authors.lastname: Suguihara
authors.forename: Karen C
authors.initials: KC
authors.lastname: Young
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001596:Benzylamines; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy*; D000080027:Cyclams; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D018496:Hyperoxia / Q000150:complications*; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007249:Inflammation; D011650:Pulmonary Alveoli / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: D001596:Benzylamines; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
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