MODS小鼠病程不同阶段脾脏树突状细胞免疫活性变化特征  

Features of changes in splenic dendritic cell immunoactivity during progression of MODS in zymosan-challenged mice

作　　者：刘茜[1] 吕艺[2] 陆江阳[1] 

机构地区：[1]解放军总医院第一附属医院病理科,北京100048 [2]解放军总医院第一附属(304医院)创伤研究室,北京100048

出　　处：《中国免疫学杂志》2014年第2期167-172,共6页Chinese Journal of Immunology

基　　金：首都医学发展科研基金(首发2011-5002-02)

摘　　要：目的：本研究观察多脏器功能障碍综合征（MODS）病程发展中脾脏树突状细胞（DC）免疫活性变化的特点,探讨脾脏DC启动免疫反应和负向免疫调节对MODS病程的影响.方法：采用酵母多糖腹腔注射复制C57 BL/6小鼠MODS模型,观察伤后不同阶段动物死亡率;用流式细胞术分析脾脏DC数量变化并检测脾脏DC表面MHC-Ⅱ类分子、共刺激分子（CD86）和共抑制分子（PD-1、PD-L1）的表达水平：ELISA法检脾脏DC培养液中IL-10和IL-12含量变化.结果：致伤后动物死亡集中出现在伤后24 ～ 48 h和10 ～ 12 d两个阶段;脾脏DC数量在伤后6h和10～12 d呈双相增高;脾脏DC的MHC-Ⅱ和CD86表达水平在伤后6～12h升高,随后逐渐降低,12d时达低谷;PD-L1/PD-1在伤后早期表达开始增加,至伤后5d和12d达峰值;脾脏DC分泌IL-12含量在病程发展中呈降低趋势,12 d时达低谷.而DC分泌IL-10在伤后5d大幅增加,12d时达峰值.结论：酵母多糖致伤后,小鼠脾脏DC的免疫活性经历了由增强到耐受的演变过程,伤后早期脾脏树突状细胞免疫活化和晚期的免疫耐受与MODS病情密切相关.Objective：To investigate the changes of mice splenic dendritic cells function/immunoactivity induced by zymosan peritoneal injection,and its effect on the development of multiple organ dysfunction syndrome （MODS）.Methods：MODS was induced in adult C57BL/6 mice via intraperitoneal injection of zymosan.The Mortality was observed within 12 d following zymosan challenged.The account of splenic DC and the expression levels of MHC-Ⅱ,CD86,PD-L1,PD-1 and PIR-B on the DC were measured at the different stages of the development of MODS.Additionally,the amount of secreted IL-12 and IL-10 from isolated and cultured DC was determined.Results：After zymosan challenged,serum ALT,BUN,Cr and CK were enhanced and maintained at the high level during the period of 12 h to 48 h,recovered to normal level after 5 d,while increased again at 10-12 d.The occurrence of death peaks was 24-48 h and 10-12 d following challenged.After zymosan injection,the number of splenic DC was enhanced biphasically at 6-12 h and 10-12 d; the expression levels of MHC-Ⅱ and CD86 on the DC were increased at 6-12 h,then gradually decreased,and arrived at the lowest at 12 d.Expressions of PD-L1 and PD-1 on the DC were upregulated after zymosan challenged,which were expressed at high levels at 5 d and 12 d.During the development of MODS,it was shown that the secretion of IL-12 from the isolated splenic DC was decreased and arrived at the lowest at 12 d,but the release of IL-10 was increased and arrived at the peak at 12 d.Conclusion：After being challenged by zymosan in mice,the splenic DC function was changed from the enhancement to the tolerance,both immunoactivation at early stage and immunosuppression at late stage of the splenic DC were associated with the severity of MODS.

关 键 词：多脏器功能障碍综合征 脾脏树突状细胞 共刺激 共抑制分子 免疫球蛋白样受体-B 

分 类 号：R392.32[医药卫生—免疫学]