Modulation of epithelial permeability by extracellular macromolecules

Epithelia are sheets of cells joined together by tight junctions. This geometry allows an epithelium to act as a barrier, i.e., restrict the movement of substances between two compartments that it separates (typically 1 compartment is the blood) and also to actively and selectively transport substances between the two compartments. It has been known for a number of years that both the barrier and transport functions of epithelia can be regulated by hormones and neurotransmitters, and this regulation is a central component of plasma electrolyte and nonelectrolyte homeostasis. Less appreciated is that these epithelial functions can be modified by macromolecules other than neurotransmitters and hormones. These macromolecules have been divided into the following categories: proteases, cytokines, cellular constituents, nonbacterial xenobiotics, and bacterial xenobiotics. Such macromolecules can alter epithelial transport and barrier function by a number of different mechanisms. These include proteolysis of epithelial ion channels and tight junctional complexes, conversion of an ion pump into a nonselective cation channel, increase in epithelial membrane permeability resulting in cell swelling and lysis, and up- or downregulation of cellular second messenger systems that can alter ion transport capabilities or prove cytotoxic to the cells. Finally, these modifications can be either transient or chronic in nature and in many circumstances result in a perturbation of the electrolyte and nonelectrolyte status of the host organism.