摘要
目的观察前列腺素E2(PGE2)对体外培养的乳腺癌抗原负载小鼠树突状细胞(DC) 迁移能力及抗乳腺癌免疫作用的影响。方法用重组小鼠粒细胞巨噬细胞集落刺激因子和重组小鼠白细胞介素-4培养BALB／c小鼠骨髓来源DC,负载乳腺癌抗原后加入PGE2,进行表型、 CCR7mRNA及蛋白、同种异体混合淋巴细胞反应、特异性淋巴细胞(CTL)杀伤活性测定。将TM40D 接种于小鼠左侧胸壁皮下制作乳腺癌动物模型,1周后皮下接种PGE2组及对照组DC,观察肿瘤抑制状况。结果体外实验显示,PGE2不影响DC的刺激淋巴细胞增殖能力和同种异体特异性杀伤活性。与对照组DC相比,PGE2培养组DC的CD80、CD86阳性细胞数增多,CCR7mRNA和蛋白表达上调(P<0．05)。体外趋化试验显示,PGE2使DC对其配体CCL19和CCL21反应性增强(P<0．05)。在乳腺癌动物模型中,PGE2培养组DC抑制肿瘤生长作用优于对照组。结论 PGE2可以通过促进 DC成熟并促进其体内迁移能力,提高抗乳腺癌DC疫苗的功效。
Objective To promote the migratory ability and immunological effect of bone marrnwderived dendritic cells （BMDC） loaded with breast carcinoma antigen. Methods DCs were cultured by the medium containing rmGM-CSF and rmIL-4. After loaded with breast carcinoma antigen, DCs were stimulated with PGE2 for lday. CD86, CD80, and CCR7 were measured by flow cytometry. The expression of CCR7 on surface of BMDC was also detected by RT-PCR and Western blotting. The chemotaxis assay was measured by migration through a polycarbonate filter in transwell chambers. The competence of inducing mixed lymphocyte response （MLR） and specific cytotoxic T lymphocyte （CTL） were detected with MTT. The effect of DC blocking tumor growth in breast carcinoma model were also studied. Results Compared with control group, PGE2 upregulated surface markers of CD86, CD80, and CCR7 （P 〈0. 05）, but had no effect on MLR and CTL. PGE2 enhanced the expression of CCR7mRNA and protein （P 〈 0.05 ）. In vitro chemotaxis assay, DC stimulated with PGE2 were more sensitive to the CCR7-1igands CCL19 and CCL21 than that of control group （P 〈 0. 05）. PGE2 group vaccine had high efficacy on suppressing growth of mouse TM40D cells than that of other groups in vivo （ P 〈 0.05）. Conclusion PGE2 promotes maturation and migration of DC, and promotes specific anti-breast carcinoma immunological effect.
出处
《中华普通外科杂志》
CSCD
北大核心
2006年第5期367-369,共3页
Chinese Journal of General Surgery
关键词
乳腺肿瘤
受体
趋化因子
免疫治疗
树突细胞
Breast neoplasms
Receptor, chemokines
Immunological therapy
Dendritic cells
