Submitted on April 21, 2003
Accepted on December 10, 2003
Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small intestinal mucosa that is inhibited by MAdCAM-1
Toshiko Ogawa1, Soichiro Miura2, Yoshikazu Tsuzuki2, Takashi Ogino1, Ken Teramoto1, Toshiaki Inamura1, Chikako Watanabe1, Ryota Hokari2, Hiroshi Nagata1, and Hiromasa Ishii1*
1 Department of Internal Medicine, Keio University, School of Medicine, Tokyo, Japan
2 Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan
* To whom correspondence should be addressed. E-mail: hishii{at}sc.itc.keio.ac.jp.
Few models have described a chronic food allergy with morphological changes in the intestinal mucosa. Here, we established an ovalbumin (OVA)-induced, cell-mediated allergic rat model, and examined lymphocyte migration in the gut. Brown Norway rats were intraperitoneally sensitized to OVA, then given 10 mg/day of OVA by gastric intubation for 6 weeks. Lymphocyte subsets and adhesion molecules were examined immunohistochemically, and the migration of T lymphocytes to microvessels of Peyer's patches and villus mucosa was observed using an intravital microscope. Serum OVA-specific IgG and IgE levels were increased in animals repeatedly exposed to OVA. Significant villus atrophy and increased crypt depth was accompanied by increased infiltration of T lymphocytes in the small intestinal mucosa of the group given OVA. The expression of rat mast cell protease II and of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was also increased in these groups. The administration of anti-MAdCAM-1 antibody significantly attenuated the OVA-induced changes in the mucosal architecture and in CD4 T lymphocyte infiltration. Intravital observation demonstrated that in rats with a chronic allergy, T lymphocytes significantly accumulated in villus microvessels as well as in Peyer's patches via a MAdCAM-1-dependent process. Our model of chronic food allergy revealed that lymphocyte migration was increased with MAdCAM-1 up-regulation.
