The great big alveolar TI cell: evolving concepts and paradigms

Pulmonary alveolar type I cells (TI cell) are very large (approximately 5400 microm(2) in surface area) squamous cells that cover more than 98% of the internal surface area of rodent lungs. In the past, TI cells were believed to serve only passive barrier functions, with no active functional properties in the lung. The fairly recent development of methods to isolate TI cells has permitted investigation of functions of this cell type for the first time. Resolvable by electron microscopy, TI cells contain microvilli and organelles typically associated with metabolic functions, such as mitochondria, abundant smooth and rough endoplasmic reticulum and Golgi apparatus. TI cells contain the molecular machinery necessary for ion transport and take up Na(+), K(+), and Cl(-), from which one can infer that it is likely that they play a role in ion and fluid transport in vivo. Because the abundance/microm(2) of highly selective Na(+) channels (HSC channels, consisting of all three ENaC subunits) is the same in TI and TII cells and because TI cells cover the majority of the lung internal surface, TI cells may play the major role in bulk transport of Na(+). In vitro, TI cells can proliferate and exhibit phenotypic plasticity, raising the question of whether this cell type may play a role in development and lung repair after injury. From gene expression analysis of TI cells, one can infer a variety of other possible functions for TI cells. The development of techniques to administer transgenes specifically to TI cells will permit direct study of this cell type in vivo.