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-induced T cell migration to
colonic mucosa is mediated by MAdCAM-1 and VCAM-1
1 Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-8582; 2 Second Department of Internal Medicine, National Defense Medical College, Saitama 359-8513, Japan; and 3 Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71110
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-
-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- (25 µg/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, 4-integrin,
or 
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--treated colon. Spatial heterogeneity of MAdCAM-1 and VCAM-1
activation following TNF- challenge may promote specific T
lymphocyte recruitment in the inflamed colonic mucosa.
microcirculation; inflammatory bowel disease; 4-integrin; 7-integrin; lamina proprial
lymphocytes
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