title: The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.
abstract: BACKGROUND
  Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration.
  
  
  METHODS
  Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry.
  
  
  CONCLUSIONS
  Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.
authors.forename: Christina V
authors.initials: CV
authors.lastname: Jones
authors.forename: Maliha A
authors.initials: MA
authors.lastname: Alikhan
authors.forename: Megan
authors.initials: M
authors.lastname: O'Reilly
authors.forename: Foula
authors.initials: F
authors.lastname: Sozo
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Williams
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
authors.forename: Graham
authors.initials: G
authors.lastname: Jenkin
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Ricardo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018496:Hyperoxia / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008168:Lung / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000503:physiopathology; D055370:Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D012119:Respiration; D012129:Respiratory Function Tests; D013997:Time Factors
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor