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Articles in PresS, published online ahead of print May 29, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00026.2002
Submitted on January 18, 2002
Accepted on May 13, 2002
-induced T-lymphocyte migration to the colonic mucosa is mediated by MAdCAM-1 and VCAM-1
1 Department of Internal Medicine, Keio University, School of Medicine, Tokyo, Japan
2 Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan
3 Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA, USA
* To whom correspondence should be addressed. E-mail: miura{at}me.ndmc.ac.jp.
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 tumor necrosis factor (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- (25µg/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 MAdCAM-1, VCAM-1, 4-integrin, or ß7-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.
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