Protective role of small intestinal mucin producing cells against intestinal helminths

小肠粘蛋白产生细胞对肠道蠕虫的保护作用

• 批准号: 03670198
• 负责人: NAWA Yukifumi
• 金额: $ 1.28万
• 依托单位: Miyazaki Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670198/
• 关键词: intestinal helminths; animal model; defense mechanisms; mast cells; goblet cells; mucins; sugar moieties; 林細胞; Nippostrongylus brasiliensis; 小腸; レクチン; 糖鎖; 寄生虫; 感染防御

To determine possible importance of qualitative/quantitative changes of small intestinal goblet cell mucins in the mucosal defense, experiments were focused on the following 2 points:1) Establishment of animal models showing selective expulsion against different intestinal helminths. 2) Development of in vivo and in vitro assay system to measure protective role of goblet cell mucins.Establishment of animal modelsWhen nude mice were infected concurrently with S. ratti(Sr) and N. brasiliensis(Nb) and then trated with recombinant murine IL-3, only Sr, but not Nb, was expelled in association with intestinal mastocytosis. Sr infection was extremely prolonged in mast cell-deficient W/W^<nu> mice, though expulsion of Nb from W/W^<nu> mice delayed only 48 hrs. Delayed expulsion of Sr, but not of Nb, from W/W^<nu> mice was normalized by bone marrow grafting. After concurrent infection with Nb and Sr or S. venezuelensis in Mongolian gerbils, Strongyloides spp. survive over 2 mo. while Nb expelle … More d within 3 weeks. Thus, these 3 models can be used as the animal model showing selective expulsion against intestinal helminths.Development of assay system to assess protective role of goblet cell mucinsGoblet cell hyperplasia and alterations of sugar terminals of mucins were induced and all implanted worms were expelled within 5 days when 13 day-old "Damaged" Nb adult worms were implanted intraduodenally into normal recipient rats. When 7 day-old "Normal" worms were implanted into these rats having goblet cell changes, all implanted "Normal" worms, which were supposed to parasitize over 10 days, were expelled within 48 hr. When the same experiment was carried out using hypothymic rnu/rnu rats, alterations of sugar terminals of goblet cell mucins, but not hyperplasia of the cells, was induced by intraduodenal implantation of "Damaged" worms in association with complete expulsion of the worms. Subsequently implanted "Normal" worms were expelled within 48 hrs. These results imply that once Nb worms were damaged by host's T cell-mediated immunity, they can induce alteration of sugar terminals of goblet mucins without T cell help and that once such changes were induced, altered mucin can act selective barrier against Nb to prevent attachment to the mucosa. Less

为了确定小肠杯状细胞粘蛋白在粘膜防御中的定性/定量变化的可能重要性，实验重点关注以下两点：1）建立显示针对不同肠道蠕虫的选择性排出的动物模型。 2)建立体内外检测体系，测定杯状细胞粘蛋白的保护作用。动物模型的建立当裸鼠同时感染S.ratti(Sr)和N.brasiliensis(Nb)，然后用重组鼠IL-3处理时，只有Sr被排出，而不是Nb，与肠道肥大细胞增多症相关。在肥大细胞缺陷的 W/W^<nu> 小鼠中，Sr 感染的时间极其延长，尽管从 W/W^<nu> 小鼠中排出 Nb 仅延迟了 48 小时。通过骨髓移植，W/W^nu 小鼠延迟排出Sr，但不延迟排出Nb，使其正常化。蒙古沙鼠、类圆线虫同时感染 Nb 和 Sr 或 S. venezuelensis 后。存活超过2个月。而 Nb 在 3 周内排出。因此，这3种模型可以用作显示针对肠道蠕虫的选择性驱除的动物模型。开发测定系统以评估杯状细胞粘蛋白的保护作用当将13日龄的“受损”Nb成虫十二指肠内植入正常受体大鼠时，诱导杯状细胞增生和粘蛋白糖末端的改变，并且所有植入的蠕虫在5天内被驱除。当将 7 天大的“正常”蠕虫植入这些发生杯状细胞变化的大鼠体内时，所有植入的“正常”蠕虫（本应寄生超过 10 天）在 48 小时内被排出。当使用低胸腺rnu/rnu大鼠进行相同的实验时，通过在十二指肠内植入“受损”蠕虫并与蠕虫的完全排出相关，诱导了杯状细胞粘蛋白的糖末端的改变，而不是细胞的增生。随后植入的“正常”蠕虫在 48 小时内被排出。这些结果表明，一旦Nb蠕虫被宿主T细胞介导的免疫损伤，它们可以在没有T细胞帮助的情况下诱导杯状粘蛋白糖末端的改变，并且一旦诱导这种变化，改变的粘蛋白可以对Nb发挥选择性屏障，以防止其附着在粘膜上。较少的

项目成果

Horii, Y., Khan, A. I. and Nawa, Y.: "Persistent infection of Strongyloides venezuelensis and normal expulsion of Nippostrongylus brasiliensis in Mongolian gerbils, Meriones unguiculatus, with reference to the cellular responses in the intestinal mucosa."

Horii, Y.、Khan, A. I. 和 Nawa, Y.：“蒙古沙鼠（长爪沙鼠）中委内瑞拉圆线虫的持续感染和巴西圆线虫的正常排出，与肠粘膜的细胞反应有关。”

Abe,T.,Sugaya,H.Yoshimura,K.,Nawa,Y.: "Induction of the expulsion of Strongyloides ratti and retention of Nippostrongylus brasiliensis in a thymic nude mice by repetitive administration of recombinant ILー3." Immunology. (1992)

Abe，T.，Sugaya，H. Yoshimura，K.，Nawa，Y.：“通过重复施用重组 IL-3 诱导胸腺裸鼠中鼠圆线虫的排出和巴西圆线虫的保留。” 1992）

Horii, Y. and Nawa, Y.: "Peculiar phenotype and localization of mast cells in the jejunum of Mongolian gerbils and their significance to mucosal defense against intestinal helminths." Jpn. J. Parasitol. 41. 505-512 (1992)

Horii, Y. 和 Nawa, Y.：“蒙古沙鼠空肠中肥大细胞的特殊表型和定位及其对粘膜防御肠道蠕虫的重要性。”

Ishikawa, N., Horii, Y. and Nawa, Y.: "Immune-mediated alteration of the terminal sugars of goblet cell mucins in the small intestine of Nippostrongylus brasiliensis-infected rats." Immunology. 78. 303-307 (1993)

Ishikawa, N.、Horii, Y. 和 Nawa, Y.：“感染巴西圆线虫的大鼠小肠中杯状细胞粘蛋白末端糖的免疫介导改变。”

Oinuma, T., Abe, T., Nawa, Y., Kawano, J. and Suganuma, T.: "Glycoconjugates in rat small intestinal mucosa during infection with intestinal nematode, Nippostrongylus brasiliensis." Adv. Exp. Med. Biol.

Oinuma, T.、Abe, T.、Nawa, Y.、Kawano, J. 和 Suganuma, T.：“肠道线虫感染巴西圆线虫期间大鼠小肠粘膜中的糖缀合物。”