Role of intestinal permeability in monitoring mucosal barrier function. History, methodology, and significance of pathophysiology.

The intestinal barrier function is considered to play an important role in protecting the penetration of luminal antigens, associated with the development of secondary infection and sepsis and the initiation of the multiple organ dysfunction syndrome. The intestinal mucosal barrier against luminal macromolecules and microorganisms consists of both non-immunological and immunological defence mechanisms. The main constituents of the intestinal barrier are the endothelial and epithelial barriers. The epithelial barrier selectively restricts micromolecular permeation and almost completely restricts macromolecular permeation, while the endothelial barrier has a very limited restriction to micromolecules and only partly to macromolecules. Maintenance of the barrier depends on the integrity of cellular plasma membranes and tight junctions, as well as the elaboration of endothelial and epithelial secretory products. Focal denudation of the barrier results in permeation of potentially threatening luminal compounds including antigens, proteases, H+, bacteria and endotoxin, and also other factors chemotactic for inflammatory cells. By initiating inflammation and thus acting on subepithelial tissues, such factors can further influence endothelial and epithelial transport and barrier function. The repair of endothelial and epithelial injury is also complex, and both restitution and enhanced endothelial and epithelial cell proliferation are likely to be important. At present, however, mechanisms for intestinal epithelial and endothelial permeation, their alterations in disease and potential ways to prevent or repair injury, are still not fully elucidated.