Structural correlates of intestinal tight-junction permeability.

Abstract

A variety of evidence suggests that specific parameters of tight-junction structure correlate with tight-junction function. Thus, one potential indirect means of probing the functional characteristics of paracellular pathways within epithelia at the cellular level is detailed analysis of tight-junction structure and distribution. In the small intestine such structural studies are confounded by the complex geometry and cellular heterogeneity of the epithelium, but, to date, these studies suggest this epithelium may actually consist of a moderately "tight" (villus) and a "leaky" (crypt) epithelium arranged in parallel. Moreover, it is becoming clear that both the structure and function of tight junctions, including those of the small intestine, are not static. Evidence from several epithelia indicate that a variety of factors (transepithelial osmotic gradients, cyclic nucleotides, intra- and extracellular Ca+2 concentrations) are capable of modulating tight-junction structure and function. Additionally, a variety of indirect evidence suggests that the cytoskeleton of epithelial cells may interact with the tight junction and that perhaps the alterations in junctional structure and function elicited by some of the above factors may be mediated via effects of these agents on the cytoskeleton. It may now be viewed as probable that epithelial cells have the capacity to fine-tune parameters of paracellular transport just as they do transcellular transport. We speculate that, in many instances, they may accomplish this feat by directly manipulating structural units of the tight junction via components of the cytoskeleton.