Protein traffic across lung epithelia.

Abstract

The pulmonary airspaces are lined with a continuous layer of epithelial cells. The airway epithelium consists of both ciliated and nonciliated cells and underlying gland cells, whereas the alveolar spaces are lined primarily by squamous type I cells, with a small fraction of the surface being formed by granular type II pneumocytes. As typical of all epithelia, the cells are polarized and joined by tight junctions. Both airway and alveolar epithelia have been shown to be relatively resistant to the flow of water and solutes and to absorb sodium and/or secrete chloride and perhaps other ions by active processes. Functionally, the pulmonary epithelia are representative of typical complex biologic barriers such as those in the gut and kidney. Experimental observations indicate that the pulmonary epithelial barriers exhibit pathways with functional properties of both small and large pores through which small solutes can flow. It is unclear, however, how proteins and other macromolecules are translocated across the air-blood barrier. It has been demonstrated that macromolecules are normally present in the fluid lining both airway and alveolar epithelia (I) and that the concentrations and amounts of these macromolecules are likely to change after epithelial injury (2). The presence of molecular species as diverse as immunoglobulins and albumin in alveolar fluid under normal conditions suggests that these and other proteins may play an important role in pulmonary functions and defense mechanisms. For example, albumin may contribute to the regulation of lung fluid balance because of its osmotic activity and the fact that its concentration in alveoli may in part be regulated by its potential for transcytosis. It has recently been suggested that albumin is transported by specialized transport pathwaysacross alveolar (3, 4) and airway (5) epithelia, most likely involving vesicular transport mechanisms. It has also been shown that albumin may be actively removed from the airspaces by both airway and alveolar epithelia (3-5). Immunoglobulins in airway and alveolar fluid may serve their specific functions in lung defense mechanisms. Potential antioxidant molecules may be present in alveolar lining fluid (6), perhaps as the result of transcytosis across the epithelial cells. Advances in biotechnology are providing protein and pep-