Role of G-CSF in the proliferation, differentiation and cell cycle distribution of mouse thymocytes after acute radiation / 中国实验血液学杂志

ABSTRACT

This study was purposed to investigate the effect of G-CSF on the proliferation, differentiation, and cell cycle distribution of thymocytes in sublethally irradiated mice. Female BALB/c mice were exposed to 6.0 Gy γ-ray irradiation and then randomly divided into control and G-CSF treatment group. In the treatment group rhG-CSF 100 µg/(kg·d) was given subcutaneously for 14 continuous days and to make sure the first injection was given within 1 hour after irradiation. Cell cycle distribution and apoptosis of thymocytes were detected within 72 hours after irradiation. Subpopulations of CD4(-)CD8(-) cells and sequential changes in the distribution of CD4(+)CD8(+), CD8(+)CD4(-), CD8(-)CD4(+) cells were detected by a three-color flow cytometry during a four-weeks period after irradiation. The results showed that in G-CSF treatment group marked increase of cells in G(0)/G(1) phase (G-CSF vs control 82.0 ± 5.0% vs 75.9 ± 2.8%) (p < 0.05) and a decrease of cells in S phase (G-CSF vs control 10.2 ± 4.8% vs 15.7 ± 2.3%) (p < 0.05)could be observed as early as 6 hours after irradiation, but G-CSF seems have no evident effects on the cells in G(2)/M phase. G-CSF could also protect thymocytes against apoptosis. 6 and 12 hours after irradiation the apoptosis rates of thymic cells in G-CSF treatment group were 11.5 ± 2.4% and 15.5 ± 3.3% respectively, while in the control group the apoptosis rates were 16.5 ± 2.2% and 22.6 ± 0.7% respectively. Comparison between the two group demonstrated significant difference (p < 0.05). CD4(-)CD8(-) double negative thymocytes (DN)can be defined as DN1-4 according to their maturation. G-CSF treatment resulted in a significant increase in DN1 thymocytes and promoted their proliferation and differentiation to a more mature DN3 and DN4 stage. G-CSF could enhance the recovery of CD4(+)CD8(+) thymocytes and mitigate their relapse during reconstitution. The percentage of CD4(+)CD8(+) thymocytes in the G-CSF treatment group 28 days after irradiation was significantly higher than that of the control group (71.0 ± 6.3% vs 25.5 ± 6.3%) (p < 0.05). It is concluded that G-CSF has a positive effects on the thymic cell cycle distribution, proliferation and differentiation, which may contribute to the reconstitution of central immune system after acute irradiation.