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• W2077295050 startingPage "1772" @default.
• W2077295050 abstract "Two fundamental mechanisms within alveoli are essential for lung function: regulated fluid transport and secretion of surfactant. Surfactant is secreted via exocytosis of lamellar bodies (LBs) in alveolar type II (ATII) cells. We recently reported that LB exocytosis results in fusion-activated cation entry (FACE) via P2X4 receptors on LBs. We propose that FACE, in addition to facilitating surfactant secretion, modulates alveolar fluid transport. Correlative fluorescence and atomic force microscopy revealed that FACE-dependent water influx correlated with individual fusion events in rat primary ATII cells. Moreover, ATII cell monolayers grown at air-liquid interface exhibited increases in short-circuit current (Isc) on stimulation with ATP or UTP. Both are potent agonists for LB exocytosis, but only ATP activates FACE. ATP, not UTP, elicited additional fusion-dependent increases in Isc. Overexpressing dominant-negative P2X4 abrogated this effect by ~50%, whereas potentiating P2X4 lead to ~80% increase in Isc. Finally, we monitored changes in alveolar surface liquid (ASL) on ATII monolayers by confocal microscopy. Only stimulation with ATP, not UTP, led to a significant, fusion-dependent, 20% decrease in ASL, indicating apical-to-basolateral fluid transport across ATII monolayers. Our data support the first direct link between LB exocytosis, regulation of surfactant secretion, and transalveolar fluid resorption via FACE.—Thompson, K. E., Korbmacher, J. P., Hecht, E., Hobi, N., Wittekindt, O. H., Dietl, P., Kranz, C., Frick, M. Fusion-activated cation entry (FACE) via P2X4 couples surfactant secretion and alveolar fluid transport FASEB J. 27, 1772–1783 (2013). www.fasebj.org" @default.
• W2077295050 created "2016-06-24" @default.
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• W2077295050 date "2013-01-10" @default.
• W2077295050 modified "2023-10-10" @default.
• W2077295050 title "Fusion‐activated cation entry (FACE)<i>via</i>P2X₄couples surfactant secretion and alveolar fluid transport" @default.
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• W2077295050 doi "https://doi.org/10.1096/fj.12-220533" @default.
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