Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 18, Issue 5, Pages 1693-1700Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E06-11-1052
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Funding
- NHLBI NIH HHS [R01 HL051854, HL-51856, HL-51854] Funding Source: Medline
- NIAID NIH HHS [AI-053194, P01 AI053194] Funding Source: Medline
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Many organs consist of a hollow cavity surrounded by a monolayer of epithelial cells. Despite their common structure, such organs form by diverse morphogenetic processes. Three-dimensional culture systems have been useful in analyzing the events. Most processes require a combination of cell proliferation and cell death to produce a hollow cavity. Here, we describe a new three-dimensional culture system in which primary human lung alveolar type II cells formed hollow epithelial cysts by a novel process. Individual cells moved, collided, and formed alveolar-like cysts without appreciable proliferation or apoptosis. The alveolar-like cysts consisted of a polarized monolayer of differentiated alveolar type II cells, which secreted surfactant into the central lumen. Blockage of beta 1 integrin did not alter cell movement or collision, but it greatly reduced adhesion of cells after collision and subsequent formation of alveolar-like cysts. Treatment of preformed alveolar-like cysts with forskolin increased their diameter, possibly due to stimulation of fluid secretion into the lumen. We conclude that epithelial differentiation and cyst-formation can occur without appreciable proliferation or apoptosis.
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