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蟾毒灵通过增强巨噬细胞吞噬作用增强白血病小鼠的免疫反应。

Bufalin Enhances Immune Responses in Leukemic Mice Through Enhancing Phagocytosis of Macrophage .

作者信息

Shih Yung-Luen, Chou Jiann-Shang, Chen Yung-Liang, Hsueh Shu-Ching, Chung Hsueh-Yu, Lee Mei-Hui, Chen Chao-Ping, Lee Ming-Zhe, Hou Hsin-Tu, Lu Hsu-Feng, Chen Kuo-Wei, Chung Jing-Gung

机构信息

Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C.

School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan, R.O.C.

出版信息

In Vivo. 2018 Sep-Oct;32(5):1129-1136. doi: 10.21873/invivo.11355.

Abstract

BACKGROUND/AIM: Bufalin, bufadienolide present in Chan Su, has been shown to induce cancer cell apoptosis in many human cancer cells, including human leukemia cells, but its effects on immune responses are unknown.

MATERIALS AND METHODS

This study investigated whether bufalin affected immune responses of mice with WEHI-3 cell-generated leukemia in vivo. BALB/c mice were intraperitoneally injected with WEHI-3 cells to develop leukemia and then were treated with oral treatment with bufalin at different doses (0, 0.1, 0.2 and 0.4 mg/kg) for 2 weeks. At the end of treatment, all mice were weighted and blood was collected; liver and spleen tissues were collected for cell marker, phagocytosis, natural killer (NK) cell activity and T- and B-cell proliferation measurements by using flow cytometric assays.

RESULTS

When compared with the leukemia control group, bufalin increased the body weight, but reduced liver and spleen weights, and reduced CD3, CD16 and Mac-3 cell markers at 0.4 mg/kg treatment and increased CD11b marker at 0.1 and 0.2 mg/kg treatment. Furthermore, bufalin at 0.4 mg/kg increased phagocytosis by macrophages isolated from peripheral blood mononuclear cells and at 0.1 mg/kg by those from the peritoneal cavity. Bufalin (0.2 and 0.4 mg/kg) increased NK cell cytotoxic activity at effector:target ratio of 50:1. Bufalin increased B-cell proliferation at 0.1 and 0.2 mg/kg treatment but only increased T-cell proliferation at 0.1 mg/kg. Bufalin increased glutamate oxaloacetate transaminase level at all dose treatments, increased glutamic pyruvic transaminase level only at 0.1 mg/kg treatment, but reduced the level of lactate dehydrogenase at all dose levels in mice with WEHI-3 cell-induced leukemia in vivo.

CONCLUSION

Bufalin increased immune responses by enhancing phagocytosis in mice with leukemia mice.

摘要

背景/目的:蟾酥中的蟾蜍灵(一种蟾蜍二烯羟酸内酯)已被证明能诱导多种人类癌细胞凋亡,包括人类白血病细胞,但其对免疫反应的影响尚不清楚。

材料与方法

本研究调查了蟾蜍灵对体内由WEHI-3细胞诱发白血病的小鼠免疫反应的影响。将BALB/c小鼠腹腔注射WEHI-3细胞以诱发白血病,然后用不同剂量(0、0.1、0.2和0.4mg/kg)的蟾蜍灵进行口服治疗,持续2周。治疗结束时,对所有小鼠称重并采集血液;收集肝脏和脾脏组织,通过流式细胞术检测细胞标志物、吞噬作用、自然杀伤(NK)细胞活性以及T细胞和B细胞增殖情况。

结果

与白血病对照组相比,蟾蜍灵可增加体重,但降低肝脏和脾脏重量;在0.4mg/kg治疗时,降低CD3、CD16和Mac-3细胞标志物水平,在0.1和0.2mg/kg治疗时增加CD11b标志物水平。此外,0.4mg/kg的蟾蜍灵可增加从外周血单核细胞分离的巨噬细胞的吞噬作用,0.1mg/kg的蟾蜍灵可增加从腹腔分离的巨噬细胞的吞噬作用。蟾蜍灵(0.2和0.4mg/kg)在效应细胞:靶细胞比例为50:1时可增加NK细胞的细胞毒性活性。蟾蜍灵在0.1和0.2mg/kg治疗时可增加B细胞增殖,但仅在0.1mg/kg时增加T细胞增殖。在体内由WEHI-3细胞诱导白血病的小鼠中,所有剂量治疗时蟾蜍灵均可增加谷氨酸草酰乙酸转氨酶水平,仅在0.1mg/kg治疗时增加谷氨酸丙酮酸转氨酶水平,但在所有剂量水平均可降低乳酸脱氢酶水平。

结论

蟾蜍灵通过增强白血病小鼠的吞噬作用来增加免疫反应。

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