Alveolar Epithelial Type II Cells

The two primary cell lineages that make up the endodermally-derived single-layer epithelium of alveoli are alveolar type I (ATI) cells and alveolar type II (ATII) cells. The thin, frail and flat ATI cells cover more than 95% of the alveolar surface. As they are extremely thin, they permit efficient gas exchange by virtue of their squamous morphology. The smaller and cuboidal ATII cells (approximately 9 mm in diameter, 250 mm2 surface area) are more abundant than ATI cells, representing up to 60–88% of all alveolar epithelial cells by number and usually reside at the corners of alveoli. As the cytoplasm of ATII cells contains phospholipid multilamellar bodies, they have a foamier appearance than ATI cells. They have a large central nucleus, a high density of mitochondria and are connected to neighboring cells by intercellular and tight junctions. When these polarized epithelial cells are observed at electron microscopy, they have thin projections protruding from the apical cell surface called microvilli. A wonderful description of ATII cells comes from Robert Mason, who states the role they play as the defender of the alveolus microenvironment is similar to that of a tower in a medieval crenellated wall. Indeed, ATII cells maintain the alveolar space relatively fluid-free and prevent it from collapsing by secreting a lipoprotein material called surfactant (promoting lung expansion on inspiration and preventing lung collapse on expiration), serve as progenitor cells to repopulate the alveolar epithelium after injury and play an important role in the innate immune system response. The most updated scientific contributions in the field come from bioinformatics and omics data, that have added insights to the “non-surfactant-related functions” of ATIIs, emphasizing their pivotal role in lung repair/regeneration after injury. Dysfunctional alveolar epithelium is implicated to such an extent in almost every lung disease that, of late, it has been considered a possible therapeutic target. Therefore, studying its role from a cellular perspective can provide a novel understanding of lung diseases, implying that regenerative medicine in the treatment of degenerative parenchymal lung diseases may well become a reality.