MBL抑制白假丝酵母菌诱导DC成熟和细胞因子分泌  

Mannan-Binding Lectin Inhibits Candida Albicans-Induced DC Maturation and Cytokine Secretion

作　　者：王明永[1,2] 王凡平[2] 翟晶晶[2] 李俊鹏[3] 张娜[2] 李昊典 郭康[3] 宋士军[3] 于海川[2] 赵雯瑕 李梦杰[2] 

机构地区：[1]新乡医学院三全学院,河南新乡453003 [2]新乡医学院医学检验学院,河南新乡453003 [3]新乡医学院第三附属医院,河南新乡453003

出　　处：《中国实验血液学杂志》2015年第2期517-521,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金资助项目(31100645;81373120);教育部新世纪优秀人才支持计划(NCET-13-0990);国家级大学生创新创业训练计划项目(201310472033);河南省高校科技创新人才项目(2012HASTIT024);河南省高校青年教师骨干项目(2010GGJS-117);新乡医学院2012年度研究生科研创新支持计划(YJSCX201229Y)

摘　　要：目的:探讨甘露聚糖结合凝集素(mannan-binding lectin,MBL)对白假丝酵母菌(candida albicans,C.albicans)诱导的树突状细胞(dendritic cells,DC)成熟及分泌细胞因子的影响。方法:从健康成人外周血分离能粘附塑料的单核细胞(MNC),应用常规方法体外诱导未成熟DC(im DC),然后在有或无C.albicans和不同浓度(1-20mg/L)天然人MBL条件下继续培养2 d;用倒置显微镜观察DC的形态,以FACS分析DC的表型,用ELISA检测DC培养上清中TNF-α和IL-6的含量;FACS分析MBL与C.albicans及im DC的结合,Western blot分析IκBα磷酸化及p65/NF-κB细胞核移位。结果:ELISA检测发现,高浓度MBL(10-20 mg/L)能够下调C.albicans诱导人DC表面分子CD83和CD86表达,并抑制C.albicans诱导的TNF-α和IL-6分泌;FACS检测显示,MBL不仅能够与C.albicans结合而且能够与im DC结合;Western blot分析显示,MBL对C.albicans诱导的IκBα磷酸化及p65/NF-κB细胞核移位均有显著的抑制作用。结论:MBL能够以配体结合形式通过调节NF-κB信号途径抑制C.albicans诱导的DC成熟及细胞因子分泌,提示MBL能够在C.albicans诱导的免疫反应中起调控作用。Objective：To investigate the effects of mannan-binding lectin （MBL） on the maturation and cytokine secretion of human dendritic cells （ DC ） induced by Candida albicans （ C. albicans ）. Methods The plastic-adherent mononuclear cells were prepared from the blood of healthy adult volunteers. The human peripheral blood mononuclear cells-derived dendritic cells （MNC-DC） were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4, and then cultured for 2 days in presence or absence of C. albicans at varying concentration of human MBL ranging from 1 to 20 mg/L. DC＇s shape and characters were observed under inverted microscopy, the expression of CD83 and CD86 on DC was analyzed by FACS. The levels of TNF-a and IL-6 were detected by ELISA. FACS also was used to investigate the interaction of MBL with immature DC （imDC） and C. albicans. Western blot was used to detect C. albicans-induced IKBct phosphorylation and p65/NF-KB translocation in DC. Results：MBL at higher concentrations （10- 20 mg/L） down-regulated the expression of CD83 and CD86 on the monocyte-derived dentritic cells （MoDC） induced by C. albicans, and inhibited the production of TNF-a and IL-6 induced by C. albicans. FACS showed that MBL could not only bind to C. albicans but also bind to imDCs in a Ca2＋ - dependent manner. Western blot showed that MBL could decrease the phosphorylation of IKBoL and the nuclear translocation of p65/NF-KB. Conclusion：MBL may inhibit TNF-ot and IL-6 production induced by C. albicans in DC through NF-KB signaling pathways, suggesting that MBL can play some roles in the regulation of C. albicans-induced immune response.

关 键 词：甘露聚糖结合凝集素 白假丝酵母菌 树突状细胞 细胞因子 免疫调节 

分 类 号：R392.11[医药卫生—免疫学]