大剂量γ射线对树突状细胞表型及功能的影响
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国家自然科学基金(30970679,81001221).


Effect of high dose γ-irradiation on phenotype and function of dendritic cells
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Supported by National Natural Science Foundation of China(30970679,81001221).

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    摘要:

    目的探讨大剂量电离辐射对树突状细胞(DC)表型及免疫功能的影响和辐射致免疫抑制的机制。 方法以粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白介素-4(IL-4)诱导造血干细胞产生DC,给予0、10、20、30 Gy γ射线照射,并于照后24 h进行脂多糖(LPS)处理(1 μg/ml)使之成熟。用Transwell法研究DC的迁移能力,流式细胞术检测DC表面分子(CD80、CD86、MHC-Ⅱ和CCR7)的表达,ELISA检测细胞因子(IL-6、IL-10和PGE2)的分泌。 结果大剂量γ射线对DC的表型无影响,却能抑制DC向CCL19的迁移,同时下调CCR7的表达,减少IL-6、IL-10和PGE2等细胞因子的分泌。 结论大剂量γ射线可以通过下调CCR7和诱导凋亡抑制DC的迁移,减少细胞因子的分泌,导致免疫抑制。

    Abstract:

    ObjectiveTo explore the effect of high dose γ-irradiation on the phenotype and function of dendritic cells (DCs) and to study the underlying mechanism of irradiation-induced immunosuppression. MethodsGM-CSF and IL-4 were used to generate DCs, which were then subjected to 0, 10, 20, and 30 Gy γ-irradiation. After 24 h irradiation DCs were treated with lipopolysaccharide for maturation. Then Transwell assay was used to determine the migration capacity of DCs, flow cytometry was used to detect the surface molecules on DCs (CD80, CD86, MHC-Ⅱ, and CCR7). Cytokines secretion (IL-6, IL-10, and PGE2) was determined by ELISA. ResultsHigh dose γ-irradiation showed no influence on the phenotypes of DCs, but inhibited the migration of DCs towards CCL19. Moreover, the irradiation down-regulated CCR7 expression and decreased the secretion of IL-6, IL-10, and PGE2. Conclusion High dose γ-irradiation can inhibit DC migration by reducing CCR7 and inducing apoptosis. Moreover, it can also reduce the cytokine secretion, which provide a theoretical base for irradiation-induced immune suppression.

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  • 收稿日期:2011-04-06
  • 最后修改日期:2011-04-11
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  • 在线发布日期: 2011-04-19
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