Farkas, Stefan and Hornung, Matthias and Sattler, Christine and Edtinger, Karoline and Steinbauer, Markus and Anthuber, Matthias and Schlitt, Hans J. and Herfarth, Hans and Geissler, Edward K. (2006) Blocking MAdCAM-1 in vivo reduces leukocyte extravasation and reverses chronic inflammation in experimental colitis. INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 21 (1). pp. 71-78. ISSN 0179-1958,
Full text not available from this repository. (Request a copy)Abstract
Background: Leukocyte recruitment to sites of intestinal inflammation is a crucial multi-step process, leading ultimately to the accumulation of cells in the inflamed tissue. These interactions in the gut are critically dependent on the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed on endothelial cells within the mesenteric lymph nodes and the lamina propria of the intestine. Here, we investigate the pathophysiologic role of MAdCAM-1 in the intestinal microcirculation in vivo. Methods: Using a standard mouse model, chronic colitis was established after four cycles of dextran sodium sulfate (DSS) application. MAdCAM-1 expression was investigated by immunohistochemistry and Western blotting, as well as real-time polymerase chain reaction (PCR). Intravital microscopy was used to study the role of MAdCAM-1 on leukocyte-endothelium interactions and leukocyte extravasation. Results: Significant changes in MAdCAM-1 were observed in mice with chronic DSS-induced colitis. Upregulation of MAdCAM-1 expression in chronic colitis was demonstrated on a protein and messenger ribonucleic acid (mRNA) level. Anti-MAdCAM-1 treatment lead to a marked reduction (> 60%) of leukocyte sticking and extravasation in vivo, compared to the controls. This was parallelled by a significant reduction (45%) of intestinal inflammation, as measured by the histologic grading score. Conclusion: These in vivo results demonstrate a distinct role of MAdCAM-1 in inflammatory intestinal diseases, and suggest that therapeutic strategies targeting this adhesion molecule could be useful in the treatment of chronic colitis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL-ADHESION MOLECULE-1; DSS-INDUCED COLITIS; BOWEL-DISEASE; LYMPHOCYTE ADHESION; ULCERATIVE-COLITIS; CROHNS-DISEASE; MICE; EXPRESSION; ICAM-1; OLIGONUCLEOTIDES; MAdCAM-1; experimental chronic colitis; in vivo microscopy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Mar 2021 09:13 |
| Last Modified: | 02 Mar 2021 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35182 |
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