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重组人白细胞介素-2对小鼠肺肿瘤转移的抑制作用:去唾液酸GM1阳性细胞的作用

Suppression of pulmonary tumour metastasis in mice by recombinant human interleukin-2: role of asialo GM1-positive cells.

作者信息

Hinuma S, Naruo K, Ootsu K, Houkan T, Shiho O, Tsukamoto K

出版信息

Immunology. 1987 Feb;60(2):173-9.

Abstract

Recombinant human interleukin-2 (rIL-2) suppressed metastatic tumour colony formation in the lungs of C57BL/6 mice bearing Lewis lung carcinoma (3LL). In tumour-bearing mice given rIL-2, non-specific killer cells that were cytotoxic not only against natural killer-sensitive YAC-1 cells but also against 3LL cells in an in vitro 51Cr-release assay were concomitantly induced as tumour metastasis was suppressed. These non-specific killer cells were mostly removed by treatment with anti-Thy 1.2 or anti-asialo GM1 antibody plus complement (C) in vitro but not with anti-Lyt 1.2 or anti-Lyt 2.2 plus C, indicating that they were positive for Thy 1 and asialo GM1 but not for Lyt 1 and Lyt 2. In order to explore the mechanism by which rIL-2 suppressed tumour metastasis, we examined the clearance of intravenously injected 51Cr-labelled 3LL cells in the lungs of mice given rIL-2. The rate of tumour cell clearance was increased. This enhanced clearance was almost completely removed by injecting anti-asialo GM1 antibody. In addition, the injection of anti-asialo GM1 antibody also depleted most of the non-specific killer cells induced by administering rIL-2. These results indicate that asialo GM1-positive cells are not only cytotoxic in vitro but also play a critical role in the clearance of 3LL cells in the lungs in vivo. Our results indicate that asialo GM1-positive cells play an important role as anti-metastatic effector cells in suppressing the metastasis of 3LL cells in mice given rIL-2.

摘要

重组人白细胞介素-2(rIL-2)可抑制携带Lewis肺癌(3LL)的C57BL/6小鼠肺内转移性肿瘤集落的形成。在给予rIL-2的荷瘤小鼠中,随着肿瘤转移受到抑制,同时诱导出了非特异性杀伤细胞,这些细胞在体外51Cr释放试验中不仅对自然杀伤敏感的YAC-1细胞具有细胞毒性,而且对3LL细胞也具有细胞毒性。这些非特异性杀伤细胞在体外经抗Thy 1.2或抗唾液酸GM1抗体加补体(C)处理后大多被清除,但经抗Lyt 1.2或抗Lyt 2.2加C处理则不然,这表明它们Thy 1和唾液酸GM1呈阳性,但Lyt 1和Lyt 2呈阴性。为了探究rIL-2抑制肿瘤转移的机制,我们检测了给予rIL-2的小鼠肺内静脉注射的51Cr标记的3LL细胞的清除情况。肿瘤细胞清除率增加。注射抗唾液酸GM1抗体几乎完全消除了这种增强的清除作用。此外,注射抗唾液酸GM1抗体也耗尽了大部分由给予rIL-2诱导产生的非特异性杀伤细胞。这些结果表明,唾液酸GM1阳性细胞不仅在体外具有细胞毒性,而且在体内肺内3LL细胞的清除中起关键作用。我们的结果表明,唾液酸GM1阳性细胞作为抗转移效应细胞在抑制给予rIL-2的小鼠中3LL细胞的转移方面发挥着重要作用。

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