Protective role of small intestinal mucin producing cells against intestinal helminths

为了确定小肠杯状细胞粘蛋白质的质/量变化在粘膜防御中的可能重要性，实验集中在以下两点：1）建立显示对不同肠道蠕虫选择性排出的动物模型。2)杯状细胞粘蛋白保护作用的体内外检测体系的建立。ratti（Sr）和拟步甲N.结果表明，重组鼠IL-3可诱导大鼠小肠肥大细胞增多症，而Sr则不能诱导Nb的排出。Sr感染在肥大细胞缺陷的W/W^小鼠中极其延长<nu>，尽管Nb从W/W^小鼠中排出<nu>仅延迟48小时。通过骨髓移植使W/W^小鼠中Sr的延迟排出而不是Nb<nu>的延迟排出正常化。在Nb和Sr或S同时感染后。在蒙古沙鼠中的委内瑞拉线虫、类圆线虫属（Strongyloides spp.）存活2个月以上。当Nb排出时 ...更多信息 D在3周内。评价杯状细胞粘蛋白保护作用的实验系统的建立将13日龄的“受损”Nb成虫植入正常受体大鼠的尿道内，诱导杯状细胞增生和粘蛋白糖末端的改变，所有植入的蠕虫在5天内被排出。当将7日龄的“正常”蠕虫植入这些具有杯状细胞变化的大鼠中时，所有植入的“正常”蠕虫（假定寄生超过10天）在48小时内被排出。当使用胸腺功能低下的rnu/rnu大鼠进行相同的实验时，杯状细胞粘蛋白的糖末端改变，但细胞不增生，由十二指肠内植入“受损”蠕虫并完全排出蠕虫引起。随后植入的“正常”蠕虫在48小时内排出。这些结果表明，一旦Nb蠕虫被宿主的T细胞介导的免疫损伤，它们可以诱导杯状粘蛋白的糖末端的改变，而无需T细胞的帮助，并且一旦这种改变被诱导，改变的粘蛋白可以对Nb起选择性屏障作用，以防止附着到粘膜上。少

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