Activation of Intestinal Mucosal Immunity in Tumor‐bearing Mice by Lactoferrin
Activation of Intestinal Mucosal Immunity in Tumor‐bearing Mice by Lactoferrin
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乳铁蛋白激活荷瘤小鼠的肠粘膜免疫
DOI：
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
H. Tsuda
中科院分区：
文献类型：
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作者：
Wen;M. Iigo;J. Sato;K. Sekine;I. Adachi;H. Tsuda
我们之前已经证明，口服牛乳铁蛋白（bLF）可显着增加荷瘤小鼠血液中的 CD4+ 和 CD8+ T 细胞以及 NK (asialoGM1+) 细胞，并增强抗转移活性。在本文中，我们记录了口服 bLF 和 bLF 水解产物 (bLFH) 与小鼠小肠淋巴组织和固有层中 CD4+ 和 CD8+ T 以及 asialoGM1+ 细胞的强烈增加有关，特别是在皮下植入 Co26Lu 细胞的荷瘤动物中。此外，bLF和bLFH也显着增加了小肠固有层中的IgM+和IgA+ B细胞。牛脱铁转铁蛋白（bTF）没有表现出这种活性。在结肠中，bLF 处理后仅 CD8+ 细胞显着增加，而 asialoGM1+ 细胞显着减少。 bLF 和 bLFH 诱导细胞因子激活 T、B 和 asialoGM1+ 细胞。施用 bLF 和 bLFH（而非 bTF）可增加小肠粘膜中白介素-18 (IL-18)、干扰素-γ (IFN-γ) 和 caspase-1 的产生。在小肠上皮细胞中发现了特别高水平的 IL-18。此外，施用 bLF 和 bLFH（而非 bTF）可诱导小肠中 IFN-γ 呈递细胞。 Caspase-1 将 proIL-18 加工成成熟的 IL-18，在 bLF 和 bLFH 治疗后，小肠上皮细胞中也被诱导，但 bTF 则没有。这些结果表明，通过 bLF 治疗增强 IL-18 和 IFN-γ 的产生以及 caspase-1 的诱导可能对于提高肠粘膜免疫力很重要。
We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly increases CD4+ and CD8+ T cells and NK (asialoGM1+) cells in the blood of tumor‐bearing mice and enhances anti‐metastatic activity. In this paper, we document that oral administration of bLF and bLF‐hydrolysate (bLFH) is associated with strong increases in CD4+ and CD8+ T, as well as asialoGM1+ cells in lymphoid tissues and lamina propria of the small intestine in mice, especially in tumor‐bearing animals in which Co26Lu cells were implanted subcutaneously. Moreover, IgM+ and IgA+ B cells in lamina propria of the small intestine were also significantly increased by bLF and bLFH. Bovine apo‐transferrin (bTF) did not exhibit such activity. In the colon, only CD8+ cells were significantly increased by treatment with bLF, while asialoGM1+ cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1+ cells. Administration of bLF and bLFH, but not bTF, increased production of interleukin‐18 (IL‐18), interferon‐gamma (IFN‐γ) and caspase‐1 in the mucosa of the small intestine. Particularly high levels of IL‐18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, but not bTF, induced IFN‐γ presenting cells in the small intestine. Caspase‐1, which processes proIL‐18 to mature IL‐18, was also induced in the epithelial cells of the small intestine following treatment with bLF and bLFH, but not with bTF. These results suggest that enhanced production of IL‐18 and IFN‐γ and caspase‐1 induction by treatment with bLF may be important for elevation of intestinal mucosal immunity.