OGUCHI Satoshi Juntendo Univ.School of Med., Dept.of Pediatrics, Assistant, 医学部, 助手 (30214092)
SHIMIZU Toshiaki Juntendo Univ.School of Med., Dept.of Pediatrics, Lecturer, 医学部, 講師 (30260889)
|Budget Amount *help
¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
In order to clarify the mechanism of delayd- and early-type hypersensitive reactions in intestine, as well as the ulcerative colitis, we generated these animal models and exapmined the morphological and immunological reactions in these models. We have also investigated whether a change of dietary fatty acid composition affects leukotriene synthesis and mucosal damage in the intestine by using these models fed with specially designed diets prepared from soybean oil, perilla oil, corn oil, and 1/8th volume of corn oil (low fat diet).
Delayd-type hypersensitive mice model. The model was prepared by feeding ovalbumin to BALB/c mice after intraperitoneal injection of cyclophosphamide. Villous atrophy, crypt hyperplasia, so called mucosal damage, and increased numbers of intraepithelial lymphocytes (IELs) were confirmed in the antigen-challenged hypersensitive mice as seen in food-sensitive enteropathy in humnas. In these mice, we found that IELs and LPLs, which are CD4- and CD8-positive cell
s as well as TCR-alpha/beta-positive cells that have migrated from peripheral blood, are activated by orally administered antigens and cause mucosal damage in the food-sensitive enteropathy. We have also found that reducing cell membrane levels of n-6 fatty acids by feeding less n-6 fatty acids or supplementing n-3 fatty acids by feeding mice model with specially designed diets, is important to suppress leukotriene biosynthesis for prevention from mucosal damage in food-sensitive enteropathy.
IgE-mediated hypersensitive mice model. A mouse model was generated by subcutaneous implantation of the murine hybridoma producing monoclonal anti-TNP IgE antibody. In these mice model, diarrhea, mucosal edema, and a decrease of subcutaneous blood flow were observed after the antigen challenge. An increase in occurrence of mast cells and IgE-bearing cells in the lamina propria of the intestinal mucosa and a substantial increase in serum histamine level were observed after the antigen challenge. These findings suggested that oral administration of the antigen actually induced anaphylactic shock in our mouse model. This reaction was most likely to be mediated by mast cell activation, in response to the IgE-antigen complex. We have also found that the perilla-oil diet and low-fat diet were effective to prevent intestinal mucosa from these reactions.
Ulcerative colitis rat model. A rat model was generated by feeding rats with dextran-sulfate sodium. Diarrhea, bloody stool and crypt abscess were confirmed in these rats. Leukotriene production and the decrease of mucosal blood flow was prevented by feeding these rats with perilla-oil diet. We have also found that it was more effective with vitamin E and could keep rats free from mucosal damage. Less