Effects of myeloid cell-specific knockout of G-CSFR on the progression of acute radiation pneumonitis in mice

To investigate the impact of myeloid cell-specific knockout of the granulocyte colony-stimulating factor receptor (G-CSFR) on the progression of acute radiation pneumonitis.

Myeloid cell-specific G-CSFR knockout (G-CSFR^{-/-, Lyz2-cre}) mice were constructed. G-CSFR^{-/-, Lyz2-cre} and C57BL/6N mice underwent a single whole-body irradiation with 6.5 Gy of ⁶⁰Co γ-rays to establish a model of radiation injury. The lung function of mice was assessed using a mouse lung function test system at 3, 7 and 14-days post γ-ray irradiation. Pathological changes in the lung tissue were analyzed via hematoxylin and eosin (HE) staining of paraffin sections. Tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels were measured via radioimmunoassay. IL-8 and its receptor CXCR2 were quantified using enzyme-linked immunosorbent assay (ELISA). The infiltration of neutrophils in lung tissue was evaluated by immunohistochemical detection of myeloperoxidase.

At 3-, 7- and 14-days post-irradiation with 6.5 Gy of ⁶⁰Co γ-rays, there were no significant differences observed in lung function or interstitial inflammatory lesions between G-CSFR^{-/-, Lyz2-cre} mice and C57BL/6N mice. However, the infiltration of neutrophils in lung tissue of G-CSFR^{-/-, Lyz2-cre} mice was significantly reduced (P＜0.01), and the levels of IL-8, CXCR2 and TNF-α in lung tissues were markedly lower than in C57BL/6N mice (P＜0.05).

The myeloid cell-specific knockout of G-CSFR can effectively diminish neutrophil infiltration as well as inflammatory cytokine levels in lung tissues following radiation exposure.