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用双花扁豆凝集素(DBA)分离的小鼠脾细胞在B16黑色素瘤细胞实验性肺转移中的抗肿瘤作用

Anti-tumour efficacy of mouse spleen cells separated with Dolichos biflorus lectin (DBA) in experimental pulmonary metastasis of B16 melanoma cells.

作者信息

Okada T, Higuchi M, Takano M, Maruyama T, Imai Y, Osawa T

机构信息

Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.

出版信息

Br J Cancer. 1990 Feb;61(2):241-9. doi: 10.1038/bjc.1990.45.

Abstract

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.

摘要

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。

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