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 Gyγ射线照射,并于照后24 h进行脂多糖(LPS)处理(1μg/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。
Objective To 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.Methods GM-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.Results High dose γirradiation 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.