title: Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.
abstract: BACKGROUND
  The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation.
  
  
  OBJECTIVE
  To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD.
  
  
  METHODS
  Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.
  
  
  RESULTS
  Preterm birth was associated with an increase in the proportion of non-classical CD14(+)/CD16(+) monocytes on the day of delivery (58.9 ± 5.8% of total mononuclear cells in preterm vs 33.0 ± 6.1% in term infants, p = 0.02). Infants with RDS were born with significantly more CD36(+) macrophages compared with the CLD group (70.3 ± 5.3% in RDS vs 37.6 ± 8.9% in control, p = 0.02). At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14(+) mononuclear phagocytes in the airway (p = 0.03), but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36 (p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung.
  
  
  CONCLUSIONS
  These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom.
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Prince
authors.affiliation: Department of Child Health, Cardiff University, Cardiff, United Kingdom.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Maxwell
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom.
authors.forename: Sharonjit K
authors.initials: SK
authors.lastname: Gill
authors.affiliation: Academic Unit of Immunology and Infectious Disease, Department of Infection and Immunity, University of Sheffield, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom.
authors.forename: David H
authors.initials: DH
authors.lastname: Dockrell
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Sabroe
authors.affiliation: Department of Child Health, Cardiff University, Cardiff, United Kingdom.
authors.forename: Eamon P
authors.initials: EP
authors.lastname: McGreal
authors.affiliation: Department of Child Health, Cardiff University, Cardiff, United Kingdom.
authors.forename: Sailesh
authors.initials: S
authors.lastname: Kotecha
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom.
authors.forename: Moira K
authors.initials: MK
authors.lastname: Whyte
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D007958:Leukocyte Count; D008171:Lung Diseases / Q000175:diagnosis* / Q000209:etiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines