title: Effects of IL-4 on pulmonary fibrosis and the accumulation and phenotype of macrophage subpopulations following thoracic irradiation.
abstract: Thoracic irradiation injures lung parenchyma, triggering inflammation and immune cell activation, leading to pneumonitis and fibrosis. Macrophage polarization contributes to these processes. Since IL-4 promotes pro-fibrotic macrophage activation, its role in radiation-induced lung injury was investigated.
  
  
  
  Lung macrophage subpopulations were characterized from 3-26 weeks following exposure of WT and IL-4-/- mice to 0 or 12.5 Gray single dose thoracic irradiation.
  
  
  
  Loss of IL-4 did not prevent fibrosis, but blunted macrophage accumulation within the parenchyma. At 3 weeks following exposure, cell numbers and expression of F4/80 and CD206, an alternative activation marker, decreased in alveolar macrophages but increased in infiltrating macrophages in WT mice. Loss of IL-4 impaired recovery of these markers in alveolar macrophages and blunted expansion of these populations in infiltrating macrophages. CD206+ cells were evident in fibrotic regions of WT mice only, however Arg-1+ cells increased in fibrotic regions in IL-4-/- mice only. Radiation-induced proinflammatory Ly6C expression was more apparent in alveolar and interstitial macrophages from IL-4-/- mice.
  
  
  
  IL-4 loss did not prevent alternative macrophage activation and fibrosis in irradiated mice. Instead, a role is indicated for IL-4 in maintenance of macrophage populations in the lung following high single dose thoracic irradiation.
authors.affiliation: a Department of Pediatrics M&D Neonatology, University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Groves
authors.affiliation: a Department of Pediatrics M&D Neonatology, University of Rochester Medical Center , Rochester , NY , USA.|b Department of Environmental Medicine , University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Johnston
authors.affiliation: a Department of Pediatrics M&D Neonatology, University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Misra
authors.affiliation: b Department of Environmental Medicine , University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
authors.affiliation: a Department of Pediatrics M&D Neonatology, University of Rochester Medical Center , Rochester , NY , USA.|b Department of Environmental Medicine , University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015847:Interleukin-4 / Q000276:immunology*; D008168:Lung; D008262:Macrophage Activation / Q000276:immunology / Q000528:radiation effects; D008264:Macrophages / Q000276:immunology* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology*; D011829:Radiation Dosage; D000069079:Radiation Exposure / Q000009:adverse effects*; D017564:Radiation Pneumonitis / Q000209:etiology / Q000276:immunology*
chemical_list: D015847:Interleukin-4
keywords: IL-4; macrophage; pulmonary fibrosis; radiation