Blocking MAdCAM-1 in vivo reduces leukocyte extravasation and reverses chronic inflammation in experimental colitis
S Farkas, M Hornung, C Sattler, K Edtinger… - International journal of …, 2006 - Springer
S Farkas, M Hornung, C Sattler, K Edtinger, M Steinbauer, M Anthuber, HJ Schlitt, H Herfarth…
International journal of colorectal disease, 2006•SpringerBackground 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 …
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 …
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.
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