Effect of splenectomy on antitumor immune system in mice.
Effect of splenectomy on antitumor immune system in mice.
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发表时间：
2009
影响因子：
2
通讯作者：
Jun Higashijima;M. Shimada;Motoya Chikakiyo;T. Miyatani;K. Yoshikawa;M. Nishioka;T. Iwata;N. Kurita
中科院分区：
文献类型：
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作者：
Jun Higashijima;M. Shimada;Motoya Chikakiyo;T. Miyatani;K. Yoshikawa;M. Nishioka;T. Iwata;N. Kurita
背景脾切除术对体内抗肿瘤免疫系统的影响存在争议。CD4+CD25+Foxp3+T细胞（regulatory T cell: reg T）和NK细胞在免疫耐受和抗肿瘤免疫中发挥重要作用。脾切除术对小鼠抗肿瘤免疫系统的影响在转移诱导小鼠模型中得到评价。材料与方法实验1，脾切除无癌模型。将小鼠分为两组，一组为对照组，另一组为脾切除术组。脾切除术后第4、7、10天，取肠系膜淋巴结、肝、肺。采用流式细胞术分析各组淋巴结，计算各组淋巴细胞中reg t细胞和NK细胞的数量。采用逆转录聚合酶链反应（RT-PCR）检测肝脏和肺组织中Foxp3 mRNA的表达。实验2，脾切除肝转移模型。将结肠26细胞注入小鼠脾脏，将小鼠分为保脾组和脾切除组。注射后第4天行脾切除术。注射后第7天和第10天进行流式细胞术分析，第10天进行RT-PCR。注射后第10天，计算肝转移瘤数（>1 mm）。结果实验1，脾切除术组与对照组相比，流式细胞术分析显示肠系膜淋巴结中reg T和NK细胞数量明显减少。脾切除组第10天肝脏和第4、7天肺部Foxp3 mRNA表达显著升高。实验2：脾切除组出现肝转移。流式细胞术分析显示脾切除术对第7天和第10天的reg T数量没有影响。脾脏切除组NK细胞数量在第7天有所增加，但在第10天，各组间差异无统计学意义。RT-PCR结果显示，脾切除组第10天肝脏Foxp3 mRNA表达升高。结论脾脏在抗肿瘤免疫系统中发挥重要作用，脾切除术通过增加肝脏中Foxp3 mRNA的表达促进肝转移。
BACKGROUND The influence on the antitumor immune system after splenectomy in vivo are controversial. CD4+CD25+Foxp3+T-cells (regulatory T-cell: reg T) and natural killer (NK) cells play important roles in immunological tolerance and antitumor immunity. The influence of splenectomy on the antitumor immune system was evaluated in a metastasis induced mouse model. MATERIALS AND METHODS Experiment 1, splenectomy in a cancer-free model. The mice were divided into two groups, one control, and the other splenectomy group. At days 4, 7 and 10 after splenectomy, the mesenteric lymph node, the liver and the lung were harvested. The lymph nodes were analyzed by flow cytometric analysis and the number of reg T-cells and NK cells were calculated. Foxp3 mRNA in the liver and the lung was evaluated by reverse transcriptional polymerase chain reaction (RT-PCR). Experiment 2, splenectomy in a liver metastasis model. Colon 26 cells were injected into the spleen of mice and the mice were divided into two groups, a spleen preserved group, and a splenectomy group. Splenectomy was performed at day 4 after injection. At days 7 and 10 after injection, flow cytometric analysis, and at day 10 RT-PCR were performed. Ten days after injection, the number of liver metastases (>1 mm) was counted. RESULTS Experiment 1, in the splenectomy group the flow cytometric analysis showed a significant decrease in the number of reg T and NK cells in the mesenteric lymph nodes compared with the control group. In the splenectomy group, the Foxp3 mRNA increased significantly in the liver at day 10, and in the lung at days 4 and 7. Experiment 2, liver metastasis was observed in the splenectomy group. Flow cytometric analysis showed that splenectomy did not affect the number of reg T at day 7 and day 10. The number of NK cells increased in the splenctomy group at day 7, but at day 10, there was no significant difference between the groups. RT-PCR showed that at day 10, the Foxp3 mRNA in liver increased in the splenectomy group. CONCLUSION The spleen plays a very important role in the antitumor immune system and splenectomy enhances liver metastasis through the increase of Foxp3 mRNA in the liver.