Microbial regulation of intestinal radiosensitivity
Microbial regulation of intestinal radiosensitivity
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DOI：
10.1073/pnas.0504830102
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发表时间：
2005-09-13
影响因子：
11.1
通讯作者：
Gordon, JI
中科院分区：
文献类型：
--
作者：
Crawford, PA;Gordon, JI
我们描述了一种用伽马射线治疗无菌(GF)小鼠的方法，并将它们移植到正常或基因操作的骨髓中，同时保持它们的GF状态。这一方法表明，GF小鼠对致死性放射性肠炎具有明显的抵抗力。此外，与传统饲养的从出生就获得微生物区系的动物相比，对GF小鼠进行致命剂量的全身照射在其小肠绒毛的间质核心产生的凋亡内皮细胞和淋巴细胞明显较少。对GF和常规饲养的Rag1(-/-)小鼠的分析表明，成熟的淋巴细胞不是发生致死性放射性肠炎或微生物群相关的内皮放射敏感性增强所必需的。对缺乏空腹诱导脂肪因子(FIAF)的诺生菌基因敲除小鼠的研究表明，FIAF缺乏导致绒毛内皮细胞和淋巴细胞对辐射诱导的细胞凋亡的抵抗力丧失。FIAF是一种通常由小肠绒毛上皮分泌并受到微生物区系抑制的纤维蛋白原/血管生成素样蛋白。总之，这些发现提供了关于微生物所涉及的细胞和分子靶标的见解。肠道放射敏感性的调节。
We describe a method for treating germ-free (GF) mice with gamma-irradiation and transplanting them with normal or genetically manipulated bone marrow while maintaining their GF status. This approach revealed that GF mice are markedly resistant to lethal radiation enteritis. Furthermore, administering lethal doses of total body irradiation to GF mice produces markedly fewer apoptotic endothelial cells and lymphocytes in the mesenchymal cores of their small intestinal villi, compared with conventionally raised animals that have acquired a microbiota from birth. Analysis of GF and conventionally raised Rag1(-/-) mice disclosed that mature lymphocytes are not required for the development of lethal radiation enteritis or the microbiota-associated enhancement of endothelial radiosensitivity. Studies of gnotobiotic knockout mice that lack fasting-induced adipose factor (Fiaf), a fibrinogen/angio-poietin-like protein normally secreted from the small intestinal villus epithelium and suppressed by the microbiota, showed that Fiaf deficiency results in loss of resistance of villus endothelial and lymphocyte populations to radiation-induced apoptosis. Together, these findings provide insights about the cellular and molecular targets involved in microbial. regulation of intestinal radiosensitivity.