白三烯C_4增强小鼠骨髓来源树突状细胞迁移及肿瘤免疫治疗作用  

Leukotriene C4 promotes the migratory ability and immunological effect of mouse bone marrow-derived dendritic cells

作　　者：朱旬[1] 甄林林[1] 郑伟[1] 王汉晋[1] 王萱仪[1] 武正炎[1] 

机构地区：[1]南京医科大学第一附属医院普外科乳腺内分泌中心,210029

出　　处：《中华实验外科杂志》2006年第3期325-327,共3页Chinese Journal of Experimental Surgery

摘　　要：目的应用白三烯C_4(LTC_4)调节体外培养DC表面CCR7表达,观察对其迁移能力和抗肿瘤免疫作用的影响。方法体外培养小鼠骨髓细胞来源DC,负载乳腺癌抗原后,加入LTC_4 培养,检测其表型、CCR7表达及其功能的变化。结果与对照组相比,LTC_4组DC表达CD80、 CD86增高,CCR7 mRNA和蛋白表达上调(P<0．05),但MLR和CTL活性不受影响。LTC_4使DC 对其配体CCL19反应性增强(P<0．05)。在乳腺癌动物模型中,LTC_4培养DC抑制肿瘤生长作用比对照组好。结论以LTC_4培养可以通过增强DC表面CCR7表达,促进其在体内迁移能力,提高抗乳腺癌DC疫苗的功效。Objective To promote the expression of bone marrow-derived dendritic ceils with chemokine receptor CCR7, and its immunological effect on breast carcinoma in vivo. Methods Bone marrow-derived dendritic ceils were cultured in medium containing rmGM-CSF and rmIL-4. After loaded with breast carcinoma antigen, DC80 were stimulated with LTC4 for one day. Cellar surface molecules such as CD86, CDS0,and CCR7 were analyzed by flow cytometry. The expression of CCR7 on surface of DC also was detected by using method of RT-PCR and Western blot. The chemotaxis assay was measured by migration through a polycarbonate filter with 5-μm pore size in transwell chambers. The competence of inducing mixed lymphocyte response （MLR） and specific cytotoxic T lymphocyte （CTL） were detected by using MTT. In vlvo, mice were divided into three groups, and administered PBS or DC vaccines stimulated by LTC4 or not. The effect of DC blocking tumor growth in breast carcinoma model was investigated. Results Compared with control group, LTC4 up-regulated surface makers of CD86, CD80 and CCR7, but had no effect on MLR and CTL. In vitro chemotaxis assay revealed that DC stimulated with LTC4 were more sensitive to the CCR7-1igancLs CCL19 than control group, but not to CCL21. LTC4 enhanced the expression of CCR7mRNA and protein. The DC cultured with LTC4 could inhibit the growth of breast carcinoma more effectively than in control group. Conclusion LTC4 can up-regulate CCR7 surface expression of bone marrow-derived dendritic cells, enhance efficiency in migration toward chemokine, and promote specific anti-tumor immunological effect on breast carcinoma.

关 键 词：树突状细胞 乳腺肿瘤 趋化因子 细胞运动 免疫治疗 

分 类 号：R737.9[医药卫生—肿瘤]