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Int J Radiat Biol. 2016 Dec;92(12):754-765. Epub 2016 Sep 15.

Effects of IL-4 on pulmonary fibrosis and the accumulation and phenotype of macrophage subpopulations following thoracic irradiation.

Author information

1
a Department of Pediatrics M&D Neonatology, University of Rochester Medical Center , Rochester , NY , USA.
2
b Department of Environmental Medicine , University of Rochester Medical Center , Rochester , NY , USA.

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.

KEYWORDS:

IL-4; macrophage; pulmonary fibrosis; radiation

PMID:
27539247
PMCID:
PMC5247271
DOI:
10.1080/09553002.2016.1222094
[Indexed for MEDLINE]
Free PMC Article

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