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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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 beta -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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1.   Ashino, Y, Ying X, Dobbs LG, and Bhattacharya J. [Ca2+]i oscillations regulate type II cell exocytosis in the pulmonary alveolus. Am J Physiol Lung Cell Mol Physiol 279: L5-L13, 2000[Abstract/Free Full Text].

2.   Mason, RJ, and Voelker DR. Regulatory mechanisms of surfactant secretion. Biochim Biophys Acta 1408: 226-240, 1998[ISI][Medline].

3.   Rooney, SA, Young SL, and Mendelson CR. Molecular and cellular processing of lung surfactant. FASEB J 8: 957-967, 1994[Abstract/Free Full Text].

4.   Shannon, JM, Jennings SD, and Nielsen LD. Modulation of alveolar type II cell differentiated function in vitro. Am J Physiol Lung Cell Mol Physiol 262: L427-L436, 1992[Abstract/Free Full Text].

5.   Wirtz, HRW, and Dobbs LG. Calcium mobilization and exocytosis after one mechanical stretch of lung epithelial cells. Science 250: 1266-1269, 1990[ISI][Medline].


Am J Physiol Lung Cell Mol Physiol 279(1):L3-L3
1040-0605/00 $5.00 Copyright © 2000 the American Physiological Society




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