期刊
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
卷 92, 期 12, 页码 754-765出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/09553002.2016.1222094
关键词
IL-4; macrophage; pulmonary fibrosis; radiation
资金
- National Heart Lung and Blood Institute [ES T32 07026]
- National Institute of Allergy and Infectious Diseases [R01 AI101732-01, U19AI091036]
- National Institute of Environmental Health Sciences [P30 ES-01247]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI101732, U19AI091036] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES007026, P30ES001247] Funding Source: NIH RePORTER
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.
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