Human Pulmonary alveolar epithelial cells (PAEpiC), comprised of alveolar type I and type II epithelial cells, line more than 99% of the internal surface area of the lung. Type I cells are large squamous cells whose thin cytoplasmic extensions cover >95% of the internal surface area. They contain aquaporins and exhibit the highest osmotic water permeability of any mammalian cell type. Type II cells, which cover 2-5% of the surface area, produce, secrete, and recycle pulmonary surfactant. Type II cells contain Na+-, K+-ATPase and amiloride-sensitive epithelial Na+ channels. The currently accepted hypothesis is that Type II cells maintain pulmonary fluid homeostasis by regulating active Na+ transport in the lungs, whereas Type I cells are “inert” cells that provide solely a barrier function, rather than having active functions.

Recent studies indicate that Type I cells are also important in regulating ion and fluid transport. They are also useful tools to stablish in vitro disease models for High Throughput and High Content Screening.