Okada T, Higuchi M, Takano M, Maruyama T, Imai Y, Osawa T
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Br J Cancer. 1990 Feb;61(2):241-9. doi: 10.1038/bjc.1990.45.
Anti-tumour effector cells were generated through 4 days culture of normal C57BL/6 splenocytes in a medium containing concanavalin A supernatant and then fractionated with Dolichos biflorus lectin (DBA) into DBA+ (agglutinable with DBA) and DBA- (non-agglutinable with DBA) cells. The DBA- cells, infused intravenously into mice together with B16 melanoma cells, or adoptively transferred into mice 3 days after the injection of B16 cells, caused a marked decrease in the number of lung nodules, while the DBA+ cells exerted no effect. On the other hand, the DBA+ cells exhibited higher cytolytic activity in vitro than the DBA- cells in short-term 51Cr-release assays. Then, we analysed the mechanism of the strong anti-tumour activity of DBA- cells in vivo. We found that DBA- cells showed higher response to recombinant interleukin-2 (rIL-2) than DBA+ cells and proliferated very well with a small amount of IL-2. In addition, DBA- cells adhered more strongly to lung endothelial cells than DBA+ cells in response to rIL-1 or rTNF. Furthermore, DBA- cells produced larger amounts of macrophage activating factor (MAF) including IFN-gamma when cultured with B16 melanoma. Taken together, our results show that DBA- cells are effective in reducing experimental pulmonary metastases not only by the direct lytic activity but also by the indirect killing activity through the activated macrophage.
通过在含有伴刀豆球蛋白A上清液的培养基中对正常C57BL/6脾细胞进行4天培养来产生抗肿瘤效应细胞,然后用双花扁豆凝集素(DBA)将其分离为DBA+(可被DBA凝集)和DBA-(不可被DBA凝集)细胞。将DBA-细胞与B16黑色素瘤细胞一起静脉注射到小鼠体内,或在注射B16细胞3天后过继转移到小鼠体内,可使肺结节数量显著减少,而DBA+细胞则无此作用。另一方面,在短期51Cr释放试验中,DBA+细胞在体外表现出比DBA-细胞更高的细胞溶解活性。然后,我们分析了DBA-细胞在体内具有强大抗肿瘤活性的机制。我们发现,DBA-细胞对重组白细胞介素-2(rIL-2)的反应比DBA+细胞更高,并且在少量IL-2的作用下增殖良好。此外,在rIL-1或rTNF的作用下,DBA-细胞比DBA+细胞更强烈地黏附于肺内皮细胞。此外,当与B16黑色素瘤一起培养时,DBA-细胞产生大量包括干扰素-γ在内的巨噬细胞激活因子(MAF)。综上所述,我们的结果表明,DBA-细胞不仅通过直接溶解活性,而且通过激活巨噬细胞的间接杀伤活性,在减少实验性肺转移方面是有效的。