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Characterization of Ion and Fluid Transport in Human Bronchioles

Laboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, Université Paris V, Boulogne; INSERM U514, Reims; and Institut de Pharmacologie, Paris, France

Address correspondence to: Professeur Thierry Chinet, Laboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, Service de Pneumologie, Hôpital Ambroise Paré, 9 avenue Charles de Gaulle, 92104 Boulogne cedex, France. E-mail: thierry.chinet{at}apr.ap-hop-paris.fr

The regulation of the volume and composition of airway surface liquid is achieved through epithelial ion transport processes. In humans, these processes have been characterized in proximal but not distal airways. Segments of human bronchioles were dissected from surgically removed lung pieces. The transmural potential difference of microperfused bronchioles was inhibited by luminal exposure to amiloride and increased when exposed to the Cl secretagogues forskolin and ATP in the presence of amiloride. Human bronchiolar epithelial cells were cultured on permeable supports and studied in Ussing chambers. They generated a short circuit current (Isc) that decreased in response to amiloride and increased in response to forskolin and to ATP in the presence of amiloride. In low-Cl Kreb's Ringer bicarbonate, the baseline Isc and amiloride-induced decrease in Isc were not different, whereas the forskolin- and ATP-induced increases in Isc were smaller. Fluid transport measurement in excised bronchioles revealed a basal absorptive flow that was reduced by amiloride, whereas forskolin and ATP combined induced a secretory flow in the presence of amiloride. We conclude that human bronchioles actively absorb Na and fluid in unstimulated conditions and are capable of active Cl and fluid secretion when exposed to forskolin and to ATP.

Abbreviations: aquaporin 3, AQP3 • airway surface liquid, ASL • cystic fibrosis, CF • CF transmembrane conductance regulator, CFTR • Dulbecco's modified Eagle's medium, DMEM • short circuit current, Isc • Kreb's Ringer bicarbonate, KBR • phosphate-buffered saline, PBS • potential difference, PD • transmission electron microscopy, TEM

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