title: Hyperoxia exacerbates postnatal inflammation-induced lung injury in neonatal BRP-39 null mutant mice promoting the M1 macrophage phenotype.
abstract: BACKGROUND
  Hyperoxia exposure to developing lungs-critical in the pathogenesis of bronchopulmonary dysplasia-may augment lung inflammation by inhibiting anti-inflammatory mediators in alveolar macrophages.
  
  
  OBJECTIVE
  We sought to determine the O2-induced effects on the polarization of macrophages and the role of anti-inflammatory BRP-39 in macrophage phenotype and neonatal lung injury.
  
  
  METHODS
  We used RAW264.7, peritoneal, and bone marrow derived macrophages for polarization (M1/M2) studies. For in vivo studies, wild-type (WT) and BRP-39(-/-) mice received continuous exposure to 21% O2 (control mice) or 100% O2 from postnatal (PN) 1 to PN7 days, along with intranasal lipopolysaccharide (LPS) administered on alternate days (PN2, -4, and -6). Lung histology, bronchoalveolar lavage (BAL) cell counts, BAL protein, and cytokines measurements were performed.
  
  
  RESULTS
  Hyperoxia differentially contributed to macrophage polarization by enhancing LPS induced M1 and inhibiting interleukin-4 induced M2 phenotype. BRP-39 absence led to further enhancement of the hyperoxia and LPS induced M1 phenotype. In addition, BRP-39(-/-) mice were significantly more sensitive to LPS plus hyperoxia induced lung injury and mortality compared to WT mice.
  
  
  CONCLUSIONS
  These findings collectively indicate that BRP-39 is involved in repressing the M1 proinflammatory phenotype in hyperoxia, thereby deactivating inflammatory responses in macrophages and preventing neonatal lung injury.
authors.affiliation: Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8064, USA.
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Syed
authors.affiliation: Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8064, USA.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016764:Cell Polarity; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins / Q000502:physiology*; D018496:Hyperoxia / Q000150:complications*; D007249:Inflammation / Q000150:complications*; D008070:Lipopolysaccharides / Q000633:toxicity; D055370:Lung Injury / Q000209:etiology*; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype
chemical_list: C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D008070:Lipopolysaccharides