Abstract
The alveolar epithelium is composed of type I cells covering most of the gas-blood exchange surface and type II cells secreting surfactant that lowers surface tension of alveoli to prevent alveolar collapse. Here, we have identified a subgroup of type II cells expressing a higher level of cell surface molecule CD44 (CD44high type II cells) that composed ~3% of total type II cells in 5-10-wk-old mice. These cells were preferentially apposed to lung capillaries. They displayed a higher proliferation rate and augmented differentiation capacity into type I cells and the ability to form alveolar organoids compared with CD44low type II cells. Moreover, in aged mice, 18-24 mo old, the percentage of CD44high type II cells among all type II cells was increased, but these cells showed decreased progenitor properties. Thus CD44high type II cells likely represent a type II cell subpopulation important for constitutive regulation of alveolar homeostasis.
Highlights
BECAUSE THE LUNG ALVEOLAR epithelium is in direct contact with the environment, it has a propensity for self-repair needed to maintain the integrity of alveoli in the basal state [37]
To identify subpopulations of alveolar type II cells showing progenitor cell properties and contributing to the maintenance of alveolar epithelium, we examined the presence of cell surface markers on type II cells isolated from adult wild-type mice
Previous lineage-tracing studies using type II cell-specific promoters showed that without injury, the percentage of cells lineage-labeled with the type II marker surfactant protein-C (Sp-C) stayed constant over a long period, indicating that type II cells are replenished by self-renewal of Sp-Cϩ cells during the steady-state condition, rather than being derived from other cell types [1, 4]
Summary
BECAUSE THE LUNG ALVEOLAR epithelium is in direct contact with the environment, it has a propensity for self-repair needed to maintain the integrity of alveoli in the basal state [37]. In Pseudomonas aeruginosa-induced pneumonia, a subpopulation of stem cell antigen-1-positive (Sca-1ϩ) type II cells were identified having higher potential for differentiation into type I cells compared with Sca-1Ϫ counterparts [21, 22] These type II subgroups displayed a distinct progenitor property only during alveolar epithelial injury, raising the question of whether there is a type II cell population responsible for maintaining alveolar epithelial homeostasis in the basal state. These type II cells expressed a higher level of the transmembrane glycoprotein CD44 [41] and showed progenitor properties in uninjured lungs. These results point to a role of CD44high type II cells in replacing lost alveolar epithelial cells and thereby contributing to steady-state alveolar homeostasis
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