EDITORIAL
Life in the alveolus: who's in charge?
Ward R.
Rice
American Journal of Physiology-, Lung Cellular and Molecular Physiology, July 2000, Volume 279 (23)
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ARTICLE |
SURFACTANT PRODUCED in the alveolus of the lung is
required for normal lung function in all air-breathing mammals.
Composed of phospholipids and proteins, surfactant is produced in
alveolar type II cells and stored in lamellar bodies. These unique
secretory granules are then released in response to various stimuli.
Since the advent of methodologies to prepare type II cells in high
yield and purity, numerous factors have been identified that modulate secretion of lamellar bodies in vitro. Protein kinase C, protein kinase
A, and cytosolic calcium have all been identified as participants in
the regulation of surfactant secretion, either alone or in combination
(2, 3). Various agents that activate
these second messengers have also been identified and include
purinoceptor agonists and
-adrenergic agonists. In addition, stretch
of isolated alveolar type II cells also mobilizes cytosolic calcium to
cause surfactant secretion in vitro (5). However, despite
these in vitro studies, factors regulating normal surfactant secretion in vivo remain enigmatic. Isolated type II cell preparations also alter
normal cell-cell interactions present in the alveolus that may be
important for regulation of normal type II cell functions as discussed below.
Although the alveolar type II cell has been intensely studied in vitro,
type I cells have not been subjected to the same scrutiny. This is true
despite the prominent position of the thin, attenuated type I cell
occupying a majority of the surface area in the alveolus. Type I cell
primary cultures have not proved feasible to date. Type II cells in
primary culture do develop type I cell features depending on the
culture matrix but retain type II cell characteristics as well
(4). Because of their shape, type I cells are postulated to allow gas exchange to occur across the alveolar surface. However, other functions of the type I cell in the alveolus have not been proposed because of prior difficulties in studying this cell in vitro.
In this issue of the American Journal of Physiology-Lung Cellular
and Molecular Physiology, Ashino et al. (1) finally
provide some insight into the function of the type I cell in the
alveolus. Using techniques developed in their laboratory, these
investigators have examined for the first time surfactant secretion at
the level of the intact alveolus in an isolated perfused rat lung.
After a single stretch of the alveolus to 90% of inspiratory reserve volume, calcium transients that cause secretion of lamellar bodies are
produced in alveolar type II cells as previously observed in isolated
type II cells in vitro (5). However, a novel finding of
this work is production of these calcium oscillations by the type I
cell. Gap junction inhibitors, which block conductance of the calcium
oscillations from the type I cells to the type II cells, block
surfactant secretion in this model system, even though the calcium
oscillations still occur in the type I cells after the stretch. These
data support the hypothesis that type I cells function as alveolar
mechanotransducers to regulate surfactant secretion from type II cells
during normal breathing in the lung.
Although further work will be needed to determine how stretch produces
calcium transients in type I cells, the work described demonstrates a
previously unrecognized function for the type I cell in the alveolus.
The described model system also demonstrates the importance of
cell-cell interactions in regulating cell function in the alveolus.
Such interactions are not approachable in isolated cell culture at
present. Based on the study of Ashino et al. (1), further
studies to examine the alveolar type I cell would appear warranted.
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Am J Physiol Lung Cell Mol Physiol 279(1):L3-L3
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