Leukocytes are attracted to the site of disease activity and play a major role in the perpetuation of inflammation in CD. During this process, leukocytes are extrava-sated from the blood into the tissues of the bowel, which takes place through a series of sequential steps: tethering, rolling, adhesion to endothelial cells, and diapedesis between endothelial cells. This sequence is dependent on specific interactions between adhesion molecules that are upregulated in intestinal inflammation. The a4 integrin dimerizes with ß1 integrin. The a4ß[ dimer (VLA-4) binds to vascular cellular adhesion molecule 1, resulting in cell migration to a number of sites including the gut and the brain. The 4 integrin also dimerizes with ß7. The a4ß7 dimer binds to muco-sal addressing cellular adhesion molecule (MadCAM) 1, which is associated with specific trafficking to the gut (Vermeire and Rutgeerts 2006).
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