Transport of Proteins and Peptides and its Regulation in Alveolar Epithelial Cells

The lung is expected as a promising administration route for protein and peptide drugs. However, information concerning alveolar absorption mechanisms of these high molecular weight drugs is lacking. The alveolar region of the lung is lined with a continuous epithelium comprising of type I and type II epithelial cells, and squamous type I cells cover 90~95% and cuboidal type II cells cover 5~10% of the alveolar surface area. Using primary cultured alveolar type II and transdifferentiated type I cells, however, it was found that type II cells would play a significant role in albumin and insulin endocytosis from the alveolar space. Functional and siRNA studies suggest that albumin is taken up by clathrin-mediated endocytosis in type II cells, while clathrin- and caveolae-independent but dynamin-dependent pathway is involved in insulin endocytosis. The approach to enhance insulin uptake by the alveolar epithelial cells and absorption from the lung is also discussed.