Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease

Leukocyte-endothelial cell adhesion is now recognized to represent an early and rate-limiting step in the leukocyte infiltration and accompanying tissue injury that is associated with acute and chronic inflammatory diseases of the gastrointestinal tract. Adhesive interactions such as leukocyte rolling, adherence, and transendothelial migration are influenced by a variety of physical, chemical, and molecular factors that ultimately result in a net up-regulation or down-regulation of the inflammatory response. Coordination of this process is made possible by the mediator-specific, time-sensitive expression of adhesion glycoproteins on the surface of leukocytes and/or vascular endothelial cells. In this review, the different families of relevant adhesion molecules that participate in the coordinated recruitment of leukocytes into inflamed tissue are described and then discussed in terms of the pathophysiological alterations observed in selected experimental models of gastrointestinal disease. These include ischemia/reperfusion injury, radiation enteritis, inflammatory bowel disease, and the inflammatory responses to substances liberated by Helicobacter pylori and Clostridium difficile.