title: Granulocyte colony-stimulating factor reduces hyperoxia-induced alveolarization inhibition by increasing angiogenic factors.
abstract: BACKGROUND
  Granulocyte colony-stimulating factor (G-CSF) is known to mobilize endothelial progenitor cells (EPCs) from bone marrow. EPCs reportedly promote neovascularization and participate in the repair of lung structure in adult animals.
  
  
  OBJECTIVE
  We tested the hypothesis that G-CSF contributes to alveolar growth by increasing the production of angiogenic growth factor in the lungs of hyperoxia-exposed neonatal mice.
  
  
  METHODS
  Neonatal mice were exposed to hyperoxia (80%) or room air (RA) for 7 days and treated with G-CSF (50 μg/kg/day) or vehicle for 5 days. Blood was subjected to flow cytometry to gate for CD45(dim/-)/Sca-1(+)/CD133(+)/vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) to define the EPC population at day 7.
  
  
  RESULTS
  The percentage of EPCs in the peripheral blood and VEGF and VEGFR2 levels in the lungs of neonatal mice exposed to hyperoxia were significantly reduced compared to those of mice kept in RA. G-CSF significantly increased EPCs in the peripheral blood, and VEGF and VEGFR2 levels in the lungs of both mice exposed to hyperoxia and mice kept in RA. G-CSF restored alveolarization inhibited by hyperoxia without altering normal alveolarization under RA.
  
  
  CONCLUSIONS
  G-CSF restored alveolarization inhibited by hyperoxia in the developing lungs and this alveolarization-enhancing effect of G-CSF is associated with mobilization of EPCs and upregulation of VEGF signaling.
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Choi
authors.forename: Ee-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Han-Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Beyong Il
authors.initials: BI
authors.lastname: Kim
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Choi
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018496:Hyperoxia / Q000150:complications* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D016179:Granulocyte Colony-Stimulating Factor