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.
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Other URL: http://dx.doi.org/10.1007/s00384-004-0709-y
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.
|Institutions:|| Medicine > Lehrstuhl für Innere Medizin I|
Medicine > Lehrstuhl für Chirurgie
|Keywords:||MAdCAM-1; Experimental chronic colitis; In vivo microscopy|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||06 Dec 2006|
|Last Modified:||20 Jul 2011 20:50|