Effects of IL-4 on pulmonary fibrosis and the accumulation and phenotype of macrophage subpopulations following thoracic irradiation. (1st December 2016)

• Record Type: Journal Article
• Authors: Groves, Angela M.; Johnston, Carl J.; Misra, Ravi S.; Williams, Jacqueline P.; Finkelstein, Jacob N.
• Is Part Of: International journal of radiation biology. Volume 92:Number 12(2016:Dec.)
• Page Start: 754
• Page End: 765
• Publication Date: 2016-12-01
• Subjects: IL-4 -- macrophage -- pulmonary fibrosis -- radiation; Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.1080/09553002.2016.1222094
• Languages: English
• ISSNs: 0955-3002

Abstract

Abstract: Purpose: 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. Materials and methods: 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. Results: 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. Conclusions: 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.