树突细胞在多器官功能障碍综合征小鼠脾脏中的迁移变化及意义

Migration of splenic dendritic cells in model mice with multiple organ dysfunction syndrome

目的探讨脾脏中树突细胞(DC)的位置和数量变化在多器官功能障碍综合征(MODS)外周免疫器官损伤中的作用。方法酵母多糖腹腔注射法建立C57BL/6小鼠MODS动物模型,分为正常对照组及实验3～6h组、24～48h组、5～7d组、10～12d组。流式细胞术检测脾脏DC(CD11chigh+)的数量变化,免疫组化标记法观察脾脏中DC(CD11c+)的分布和迁移。结果对照组小鼠脾DC量很少(1.62%),主要分布在脾白髓边缘区。MODS3～6h组DC数量(2.62%)明显增多,与对照组比较差异有统计学意义(P<0.01),主要分布在脾脏白髓T细胞区,而白髓边缘区DC数相对减少;24～48h组DC含量(1.40%)较3～6h组明显减少,其分布仍以T细胞区为主;5～7d组脾DC含量(1.45%)下降至对照组水平,且在白髓T细胞区和边缘区均有表达;10～12d组脾DC含量(1.79%)再度明显升高,与对照组比较差异有统计学意义(P<0.05),主要分布区域转为白髓边缘区,白髓T细胞区仅有少量散在分布的DC。结论在MODS早期(3～48h组),脾DC大量增加并从脾脏白髓边缘区向T细胞区迁移,从而与T细胞形成大面积的密切接触,可以引发过度免疫反应;MODS晚期(10～12d组),脾脏DC多滞留在白髓边缘区,DC与T细胞仅有少量接触,可能参与了机体的免疫抑制过程。脾脏DC位置和含量的变化在机体免疫紊乱和MODS形成中可能起到了重要作用。

Objective To explore the effects of the changes in location and quantity of splenic dendritic cells （DCs） on the peripheral immune organ injuries of mice with multiple organ dysfunction syndrome （MODS）. Methods The MODS model of C57BL/6 mouse was established hy zymosan intraperitoneal injection. Fifty mice were randomly divided into groups of control, 3--6 hours, 12--48 hours, 5-- 7 days and 10--12 days post trauma （10 each）. The number of splenic DCs （CD11c^high1 ） was counted by flow cytometry, and the location and migration of splenic DCs （CD11c^1 ） were studied by immunohistochemistry labelling. Results In the control group, splenic CD11c^＋ DCs were only about 1.62% of all spleen mononuclear cells and mainly located at the margin between the splenic red pulp and white pulp. In the 3--6h group, number of splenic CD11c^- DCs （2. 62%） was more than that in control group （P〈0. 01）, and the cells mainly located in the T cell area and less in the marginal area of the spleen. In the 24--48h group, number of splenic CD11c^＋ DCs （1.40%） was less than that in 3--6h group （P〈0. 01） and no statistical difference compared with that in control group （P〉0. 05）, and mainly located in the T cell area. In the 5--7d group, splenic CD11c^1 DCs （1.45%） decreased to the level of control group, and located both in the marginal zone and T cell area. In the 10--12d group, number of splenic CDllc DCs （1.79%） was more than that in control group （P〈0. 05）, and mainly located in the margin zone. Conclusions In the early stage （the prior 48h） of MODS, splenic DCs increase markedly and migrate from the margin zone into the T cells areas, inducing excessive immunoreactions; while in the late stage （10--12d）, splenic DCs stay in the marginal zone and thereby less contact with T cells, which might participate in the immunosuppression and pathogenesis of MODS. The location and quantity of splenic DCs may play an important role in the immune disorder and pathogenesis of MODS.