|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1992 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1991 : ¥1,400,000 (Direct Cost : ¥1,400,000)
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 models
When 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
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 mucins
Goblet 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