title: In vivo demonstration of T lymphocyte migration and amelioration of ileitis in intestinal mucosa of SAMP1/Yit mice by the inhibition of MAdCAM-1.
abstract: The aetiology of Crohn's disease (CD) remains unknown. Since SAMP1/Yit mice have been reported to develop CD-like spontaneous enteric inflammation, such mice have been studied as an animal model of CD. In this study, using this model we examined T lymphocyte migration in microvessels of intestinal mucosa in vivo and the expression of adhesion molecules by immunohistochemistry. Fluorescence-labelled T lymphocytes isolated from AKR/J (control) mice were injected into the tail veins of recipient mice, and T lymphocyte migration in the postcapillary venules of Peyer's patches, submucosal microvessels, and villus capillaries of the terminal ileum was monitored using an intravital microscope. Adhesion of T lymphocytes was significantly increased in 35 week old SAMP1/Yit mice compared with that in AKR/J or 15 week old SAMP1/Yit mice. Immunohistochemical study showed increased infiltration of CD4, CD8 and beta7-integrin-positive cells and increased expression of MAdCAM-1 and VCAM-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against MAdCAM-1 and VCAM-1 significantly inhibited adhesion of T lymphocytes to microvessels of the terminal ileum, and anti-MAdCAM-1 antibody showed stronger suppressive effect than the anti-VCAM-1 antibody. Periodical administration of anti-MAdCAM-1 antibody twice a week for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice, but submucosal hypertrophy was not significantly suppressed. Anti-VCAM-1 antibody treatment failed to show significant resolution of ileitis. In addition, anti-MAdCAM-1 antibody treatment also attenuated established ileitis. The results demonstrate that, although MAdCAM-1 and VCAM-1 play an important role in T lymphocyte-endothelial cell interactions in SAMP1/Yit mice, MAdCAM-1 may be a more appropriate target for therapeutic modulation of chronic ileitis.
authors.affiliation: Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuzuki
authors.forename: H
authors.initials: H
authors.lastname: Matsunaga
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: J
authors.initials: J
authors.lastname: Miyazaki
authors.forename: R
authors.initials: R
authors.lastname: Hokari
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: A
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: S
authors.initials: S
authors.lastname: Nagao
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Miura
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D007079:Ileitis / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology*; D007150:Immunohistochemistry / Q000379:methods; D039641:Integrin beta Chains / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009088:Mucoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
chemical_list: D000906:Antibodies; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039641:Integrin beta Chains; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; C091368:integrin beta7