Spatial heterogeneity of TNF-alpha-induced T cell migration to colonic mucosa is mediated by MAdCAM-1 and VCAM-1.
Relatively little is known about how recirculation of lymphocytes through the inflamed intestinal mucosa is regulated. The aim of this study was to investigate the dynamic process of T lymphocyte-endothelial cell adhesion in TNF-alpha-challenged murine colonic mucosa by intravital microscopy. T lymphocytes from spleen (SPL) and intestinal lamina propria (LPL) were fluorescence labeled, and their adhesion to microvessels in the colonic mucosa was observed. In TNF-alpha (25 microg/kg)-stimulated colonic venules, an enhanced adhesion of SPL and LPL was demonstrated, with dominant recruitment of LPLs. The magnitude of the increased LPL adhesion was more significant in the colon than in the small intestine. These T lymphocyte interactions in the colonic mucosa were significantly reduced by blocking MAbs against either mucosal addressin cell adhesion molecule-1 (MAdCAM-1), VCAM-1, alpha(4)-integrin, or beta(7)-integrin but not by anti-ICAM-1. Immunohistochemistry revealed significant MAdCAM-1 expression in the lamina propria and VCAM-1 expression in the submucosa of TNF-alpha-treated colon. Spatial heterogeneity of MAdCAM-1 and VCAM-1 activation following TNF-alpha challenge may promote specific T lymphocyte recruitment in the inflamed colonic mucosa.
Watanabe
Chikako
C
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Miura
Soichiro
S
Hokari
Ryota
R
Teramoto
Ken
K
Ogino
Takashi
T
Komoto
Shunsuke
S
Hara
Yuriko
Y
Koseki
Seiichiro
S
Tsuzuki
Yoshikazu
Y
Nagata
Hiroshi
H
Granger
D Neil
DN
Ishii
Hiromasa
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018845:CD11 Antigens / Q000032:analysis; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003106:Colon; D005260:Female; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D039441:Integrin alpha4 / Q000032:analysis; D039641:Integrin beta Chains / Q000032:analysis; D019012:Integrin beta1 / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007413:Intestinal Mucosa / Q000098:blood supply / Q000737:chemistry / Q000166:cytology*; D007421:Intestine, Small / Q000166:cytology; D019041:L-Selectin / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000166:cytology; D009088:Mucoproteins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D014699:Venules / Q000166:cytology
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039641:Integrin beta Chains; D019012:Integrin beta1; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C091368:integrin beta7; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D039441:Integrin alpha4