Human airway epithelial tight junctions

Abstract

The flux of fluid, ions, macromolecules, and inflammatory cells across airway epithelium depends in part upon the integrity of its apico-lateral tight junctions. Without the correct balance of fluid and ions, the normal functioning of mucociliary clearance and the neural responsiveness of the airways cannot take place. Freeze-fracture electron microscopy has been used to investigate the structure of human airway tight junctions and their morphology comprehensively characterised at two airway levels (main and lobar bronchi). Further data is needed to establish if the fall in transepithelial electrical resistance found across progressively proximal disparate airway generations is correlated with an alteration in tight junction morphology. Altered epithelial permeability is associated with the development of the airway conditions: asthma, chronic bronchitis, and cystic fibrosis. However, few data have been published on the structure of tight junctions in asthma and chronic bronchitis. In patients with cystic fibrosis, airways obtained at transplantation and postmortem show a basal extension of the apico lateral tight junctional belt. This change is not unique to cystic fibrosis airways as it also occurs in non-respiratory systems postmortem. However the functional relevance of these changes remains uninvestigated and recently developed in vitro models may help answer this question. The data demonstrate that tight junctions are highly dynamic structures capable of rapid alterations in disease and in response to functional stress.