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YAC-1淋巴瘤细胞神经节苷脂的脱落与免疫调节活性

Shedding and immunoregulatory activity of YAC-1 lymphoma cell gangliosides.

作者信息

Ladisch S, Gillard B, Wong C, Ulsh L

出版信息

Cancer Res. 1983 Aug;43(8):3808-13.

PMID:6861145
Abstract

YAC-1 lymphoma cells, both when cultured in vitro and when passaged in ascites form in vivo, synthesize gangliosides (means of 22.1 and 14.7 nmol lipid-bound sialic acid isolated per 10(8) cells, respectively) with potent inhibitory effects on mitogen- and antigen-induced lymphoproliferation: 10 to 30 nmol highly purified YAC-1 gangliosides/ml caused greater than 90% inhibition of proliferative responses of murine lymphocytes to concanavalin A, lysozyme (a soluble specific antigen), and allogeneic cells (mixed-lymphocyte response). Measureable quantities of these gangliosides were shed by the tumor cells in vitro and also were recovered from the ascites fluid in vivo. Furthermore, the gangliosides isolated from ascites fluid (mean of 15.3 nmol/ml) had inhibitory activity of a magnitude similar to that of the gangliosides isolated from the tumor cells. Therefore, significant inhibition of normal lymphoproliferative responses by tumor-derived gangliosides occurred at ganglioside concentrations which are actually present in the fluid surrounding the tumor cells in vivo. These results support the hypothesis that shedding of gangliosides may serve to protect tumor cells from host immune destruction.

摘要

YAC-1淋巴瘤细胞,无论是在体外培养时还是在体内以腹水形式传代时,都会合成神经节苷脂(每10⁸个细胞分别分离出22.1和14.7 nmol脂质结合唾液酸),这些神经节苷脂对有丝分裂原和抗原诱导的淋巴细胞增殖具有显著抑制作用:每毫升10至30 nmol高度纯化的YAC-1神经节苷脂可使小鼠淋巴细胞对刀豆球蛋白A、溶菌酶(一种可溶性特异性抗原)和同种异体细胞(混合淋巴细胞反应)的增殖反应抑制率超过90%。这些神经节苷脂在体外可被肿瘤细胞释放,在体内也可从腹水中回收。此外,从腹水中分离出的神经节苷脂(平均15.3 nmol/ml)具有与从肿瘤细胞中分离出的神经节苷脂相似的抑制活性。因此,在体内肿瘤细胞周围的液体中实际存在的神经节苷脂浓度下,肿瘤来源的神经节苷脂对正常淋巴细胞增殖反应有显著抑制作用。这些结果支持了神经节苷脂的释放可能有助于保护肿瘤细胞免受宿主免疫破坏的假说。

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