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Am J Physiol Gastrointest Liver Physiol 286: G702-G710, 2004. First published December 11, 2003; doi:10.1152/ajpgi.00183.2003
0193-1857/04 $5.00
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INFLAMMATION/IMMUNITY/MEDIATORS

Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small intestinal mucosa that is inhibited by MAdCAM-1

Toshiko Ogawa,1 Soichiro Miura,2 Yoshikazu Tsuzuki,2 Takashi Ogino,1 Ken Teramoto,1 Toshiaki Inamura,1 Chikako Watanabe,1 Ryota Hokari,2 Hiroshi Nagata,1 and Hiromasa Ishii1

1Department of Internal Medicine, School of Medicine, Keio University, Tokyo, 160-8582; and 2Second Department of Internal Medicine, National Defense Medical College, Saitama, 359-8513, Japan

Submitted 21 April 2003 ; accepted in final form 10 December 2003

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 and then given 10 mg OVA/day by gastric intubation for 6 wk. 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 by 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. 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 upregulation.

Brown Norway rats; rat mast cell protease II; delayed type hypersensitivity; Peyer's patch; intercellular adhesion molecule-1


Address for reprint requests: H. Ishii, School of Medicine, Keio Univ., 35 Shinanomichi, Shijuku-Ku, Tokyo 160-8582, Japan (hishii{at}sc.itc.keio.ac.jp). Address for all other correspondence: S. Miura, Second Dept. of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan (miura{at}me.ndmc.ac.jp).






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