摘要
目的:研究趋化性细胞因子巨噬细胞炎症蛋白-1α(macrophage inflammation protein-1α, MIP-1α)在外周血中快速动员树突状细胞 (DC)前体细胞,并荷载小鼠前胃癌(MFC)抗原后,其体内的抗肿瘤免疫效应．方法:B6小鼠尾静脉注射MIP-1α,分选出外周血B220-CD11c+细胞,以GM-CSF、IL-4及 mTNF-α培养5-6 d,检测其表型和混合淋巴细胞反应;B220-CD11c+细胞荷载MFC抗原后制备成DC疫苗,经皮下回输MFC荷瘤小鼠,观察小鼠瘤体生长和存活时间,检测其体内抗肿瘤效应．未荷载肿瘤抗原的MIP-1α动员的胃癌DC疫苗、MFC肿瘤可溶性抗原和PBS缓冲液作为对照．结果:MIP-1α注射B6小鼠4 h后外周血中 B220-CD11c+细胞即升高,48 h达到高峰,占外周血单个核细胞(MNC)13．7％±0．8％．新鲜分离的B220-CD11c+细胞不具有成熟DC的特征, 经过细胞因子培养的B220-CD11c+细胞具有典型的DC表面标志,在混合淋巴细胞反应中具有极强的刺激T细胞增殖的能力．当荷载MFC 抗原后制成的DC疫苗皮下回输MFC荷瘤小鼠后,观察至第27天,MIP-1α动员的胃癌DC 疫苗和骨髓源性的胃癌DC疫苗实验组小鼠的瘤体大小分别为(2．7±0．6)cm3和(2．8±0．8) cm3,两者之间无显著性差异(P>0．05);而对照组小鼠瘤体迅速生长,瘤体大小分别为23．7± 1．7 cm3、26．4±1．9 cm3和31．2±2．2 cm3,实验组与对照组之间有显著性差异(P<0．05)．此外, 对照组小鼠在荷瘤后25 d内全部死亡,而实验组小鼠的生存期则明显延长,且治疗组小鼠在无瘤存活35 d后,再次接受MFC细胞冲击,继续观察小鼠至60 d仍存活,实验组和对照组的差异有统计学意义(P<0．05)．结论:注射MIP-1α可以直接快速动员B220- CD11c+DC前体细胞进入小鼠外周血,这些 DC前体细胞荷载MFC抗原后制成的胃癌DC 疫苗,可激活机体T细胞,产生明显的体内抗肿瘤效应．
AIM： To study the in vivo anti-tumor effects of dendritic cell （DC） precursors after being recruited in the peripheral blood by injection of macrophage inflammation protein-1α （MIP-1α） and pulsed by the mouse forestomach carcinoma cell （MFC） lysates. METHODS： B220^-CD11c^＋ cells were sorted from the peripheral blood of C57BL/6 mice after injection of MIP-1α via tail vein, and then cultured for 5-6 d in the presence of granulocyte-macrophage colony stimulating factor （GM-CSF）, interleukin-4 （IL-4） and mouse tumor necrosis factor （mTNF-α）. The phenotypes and mixed lymphocyte reaction （MLR） of these cells were assayed. DC vaccines were prepared after B220^-CD11c^＋ cells were loaded with MFC tumor antigen, and then were transfused in the mice baring MFC. The tumor size and the survival of the mice were observed. The mice treated DC vaccine without loading MFC tumor antigen, soluble MFC tumor antigen and phosphate-buffered saline were used as controls. RESULTS： The peripheral blood level of B220^-CD11c^＋ cells were increased 4 h after MIP-1α injection, and reached the peak at 48 h, accounting for 13.7% ± 0.8%. Freshly isolated B220^-CD11c^＋ cells did not show the features of mature DC, while the ones cultured with mGM-CSF, IL-4, and mTNF-1α were phenotypically identical to typical DC, gaining the capacity to stimulate the proliferation of allogenic T cells. 27 days later B220^-CD11c^＋ cells loading MFC tumor antigen were transfused in the mice challenged with MFC cells, the tumor sizes of experimental groups were 2.7 ± 0.6 and 2.8 ± 0.8 cm^3, while those of the controls were 23.7 ± 1.7, 26.4 ± 1.9 and 31.2 ± 2.2 cm^3. The difference between experimental groups and control groups was statistically significant （P 〈 0.05）. Moreover, all the mice in control groups died within 25 days after the first MFC cell challenging, while the survival periods of experimental groups were much longer. After living for 35 d with tumor free and receiving the second MFC cell challenging, the mice in experimental groups were still alive at day 60. The difference between experimental groups and control groups was also statistically significant （P 〈 0.05）. CONCLUSION： B220^-CD11c^＋ DC precursors can rapidly accumulate in the peripheral blood after injection of MIP-1α in mice. MFC cell lysates-pulsed DC vaccine can promote the anti-tumor effects of T cells in vivo.
出处
《世界华人消化杂志》
CAS
北大核心
2006年第4期387-391,共5页
World Chinese Journal of Digestology
关键词
树突状细胞
巨噬细胞炎症蛋白-1Α
抗肿
瘤
胃癌
Dendritic cells
Nacrophage inflamma- tion protein-1α
Anti-tumor
Gastric carcinoma
