他克莫斯对树突状细胞分化、成熟和功能的影响  

Effect of tacrolimus on differentiation, maturation and function of rat bone marrow-derived dendritic cells

作　　者：郑凯[1] 谭建明[1] 吴卫真[1] 杨顺良[1] 徐廷昭[1] 

机构地区：[1]南京军区福州总医院全军器官移植中心,福建福州350025

出　　处：《第四军医大学学报》2007年第15期1363-1366,共4页Journal of the Fourth Military Medical University

基　　金：福建省自然科学基金(C0510033)

摘　　要：目的:探讨他克莫斯(tacrolimus,FK506)对大鼠骨髓源性树突状细胞(DCs)分化、成熟和免疫学活性的影响.方法:收集大鼠骨髓源性DCs,加入不同浓度的FK506进行培养,采用流式细胞术行DCs表型分析,ELISA法检测培养上清中IL-12的水平并行体外混合淋巴细胞反应(MLR),观察DCs对同种T细胞的刺激能力.构建大鼠肾移植模型,于移植前7d输注FK506处理的DCs,观察移植肾存活时间.采用ELISA法检测MLR培养上清和移植大鼠血清中TH1/TH2细胞因子IFN-γ,IL-2,IL-4和IL-10的表达水平.结果:FK506对DCs表面分子(Iad,CD80和CD86)的表达无明显影响(P>0.05),而IL-12的分泌水平降低(P<0.05),并显著抑制DCs对T细胞的激活能力(P<0.05).大鼠移植肾存活时间分别为对照组(6.3±0.7)d,DCs组(7.2±1.4)d与FK506-DCs组(19.0±2.3)d,对照组与DCs组之间差异无统计学意义,而FK506-DCs组与DCs组之间差异有统计学意义(P<0.05).在体外MLR和动物实验中,FK506-DCs组与DCs组比较,IL-2,IFN-γ表达水平均显著降低(P<0.05),IL-4表达水平显著升高(P<0.05),而IL-10的表达水平在体外显著升高(P<0.05),但在动物实验中与DCs组差异无统计学意义(P>0.05).结论:FK506不影响DCs的分化与成熟,对其免疫学功能起负性调节作用.可能机制为FK506通过抑制DCsIL-12的分泌,来促使Th1/Th2亚群分化倾向于Th2方向.AIM： To investigate the effect of tacrolimus （FK506） on the differentiation, maturation and function of rat bone marrow-derived dendritic cells （DCs）. METHODS： We added taerolimus at concentrations of 5 - 20 μg/L to the DCs cul- ture and checked the expressions of activation markers （ Iad, CD80 and CD86） by flow cytometry, the release of cytokines IL- l2 by ELISA and the stimulatory capacity of the resulted DCs by mixed lymphocyte reaction （MLR）. Thirty Wistar rats were divid- ed into 3 groups （ n = 10 in each） ： group A accepted kidneys from SD donors; group B was infused with DCs derived from SD donors 7 d before transplantation ; group C was the same as that in group B except the DCs were treated with tacrolimus during cul- ture. The functions of the transplanted kidneys were evaluated by urine volume and ELISA was used to detect the levels of Thl/Th2 cytokines, such as IFN-y, IL-2, IL-4 and IL-10 in the MLR and in the sera of the recipients 7 d after culture or transplantation. Even at the stimulation of lipopolysaicharide （ LPS）, in the tacrolimus-treated culture, we observed no significant effects on the expressions of activation markers （Iad, CD80 or CD86）. The release of IL-12 and the stimulatory capacity of taerolimus-treated DCs were reduced, compared with control DCs （P〈0.05）. The survival time in the group A, B and C was （6.3 ＋0.7） d, （7.2＋1.4） d and （19.0＋2.3） d, respectively. Statistical analysis showed that the survival time of group C was significantly increased compared with that in group B （ P 〈 0.05 ）, but there was no significant difference between group B and A （P 〉 0. 05 ）. The levels of IFN-y/and IL-2 in group C were significantly lower than those in group B （P 〈 0.05 ）, and the level of IL-4 in group C was significantly higher than that in group B （ P 〈 O. 05 ）. The level of IL-10 in group C was significantly higher than that in group B （ P 〈 O. 05 ） in vitro, but similar in vivo （ P 〉 O. 05 ）.

关 键 词：他克莫斯 树突状细胞 免疫耐受 器官移植 

分 类 号：R392.4[医药卫生—免疫学]