Structure and function of the intestinal epithelial barrier in health and disease

The major and rate-limiting barrier to transepithelial permeation in the intestine is the intercellular tight junction. Tight junction structure is often cell type specific and general but imperfect correlates between tight junction structure and permeability exist. The structure and permeability of this key barrier is not static and can be regulated physiologically. The means of regulation appears to involve the cytoskeleton of neighboring epithelial cells (particularly absorptive cells). Meal-related solutes--nutrients such as glucose--can reversibly enhance the permeability of absorptive cell tight junctions. Although this may substantially enhance the ability of the small intestine to harvest meal-related nutrients, it is conceivable that this may also result in transient exposure of the subepithelial compartment to potentially noxious lumenal compounds. Some features found in many intestinal disease states such as PMN migration across the epithelium may also result in transient barrier defects. With PMN transmigration it is clear that even macromolecules may permeate junctions being impaled by PMNs. When disease processes finally result in focal epithelial denudation, the epithelium has the potential of resealing such defects with remarkable efficiency. The preceding discussion highlights how dynamic the tight junction is and sets the stage for future work aimed at understanding the initial signaling events and intracellular cascade(s) that allow this major barrier to demonstrate such plasticity.