DC-SIGN在慢性乙型肝炎病毒感染时树突状细胞成熟活化中的作用  

Role of DC-SIGN on the maturation and activation of dendritic cells in chronic hepatitis B virus infection

作　　者：邹小静[1] 姜雪强[1] 田德英[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院感染科,武汉430030

出　　处：《临床肝胆病杂志》2011年第2期145-147,153,共4页Journal of Clinical Hepatology

基　　金：湖北省自然科学基金项目(2008CDA049)

摘　　要：目的研究慢性HBV感染时,DC-SIGN在树突状细胞(DC)成熟和活化中介导的作用。方法将α-甘露糖苷酶抑制剂-基夫碱作用于HepG2.2.15细胞,收获上清中的高甘露糖型HBV颗粒,并于第5 d加入到外周血单核细胞衍生的DC培养基中,培养至第7 d,采用流式细胞仪检测DC表面CDla、CD83、CD80、CD86、HLA-DR分子的表达,MTT法检测DC刺激淋巴细胞增殖的能力,ELISA法检测DC分泌IL-12的水平。结果高甘露糖型HBV组,与天然的HBV组相比,DC表面CDla、CD83、CD80、CD86、HLA-DR分子的表达增加,分泌IL-12的水平升高,刺激同种异体淋巴细胞增殖的能力亦明显增强,且上述效应均可被DC-SIGN特异性抗体所阻断。结论 DC-SIGN识别高甘露糖型HBV后可以促进DC的成熟和活化,天然的HBV可能利用α-甘露糖苷酶参与的去甘露聚糖修饰来逃避DC-SIGN的识别,从而诱导DC功能的缺陷。Objective To investigate the role of DC-SIGN on the maturation and activation of dendritic cells（DC） in chronic HBV infection.Methods Highly mannosylated HBV obtained by treating HepG2.2.15 cells with the a-mannosidase I inhibitor kifunensine were added to the medium of DC derived from peripheral blood mononuclear cells on day 5 after culture.The expression rates of CDla,CD83,CD80,CD86 and HLA-DR of DCs were assayed by flow cytometry analysis,the stimulating capacity of DC was detected by MTT assay and the levels of IL-12 released by DCs were measured by ELISA on day 7.Results Compared with native HBV group,the expression of CDla,CD83,CD80,CD86 and HLA-DR of DC were significantly improved,levels of IL-12 were increased,and capacity of stimulating lymphocyte proliferation was enhanced in highly mannosylated HBV group.Furthermore these effects could be all blocked by DC-SIGN specific antibody.Conclusion DC-SIGN can promote the maturation and activation of DC after recognizing highly mannosylated HBV,native HBV may exploit demannosylation as a way to escape recognition by DC-SIGN and thereby induce DC dysfunction.

关 键 词：肝炎 乙型 慢性 肝炎病毒 乙型 树突细胞 

分 类 号：R512.62[医药卫生—内科学]