Inflammation Promotes Airway Epithelial ATP Release via Calcium-Dependent Vesicular Pathways

SEIKO F. OKADA; CARLA RIBEIRO; JULIANA I. SESMA; LUCIA SEMINARIO-VIDAL; LUBNA ABDULLAH; CATHARINA A. VAN HEUSDEN; EDUARDO R. LAZAROWSKI; RICHARD C. BOUCHER

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

AMER THORACIC SOC

Lugar: New York; Año: 2013 vol. 49 p. 814 - 820

1044-1549

ATP in airway surface liquid (ASL) controls mucociliary clearance functions via the activation of airway epithelial purinergic receptors. However, abnormally elevated ATP levels have been reported in inflamed airways, suggesting that excessive ATP in ASL contributes to airway inflammation. Despite these observations, little is known about the mechanisms of ATP accumulation in the ASL covering inflamed airways. In this study, links between cystic fibrosis (CF)? associated airway inflammation and airway epithelial ATP release were investigated. Primary human bronchial epithelial (HBE) cells isolated from CF lungs exhibited enhanced IL-8 secretion after 6 to 11 days, but not 28 to 35 days, in culture, compared with normal HBE cells. Hypotonic cell swelling?promoted ATP release was increased in 6- to 11-day-old CF HBE cells compared with non-CF HBE cells, but returned to normal values after 28 to 35 days in culture. The exposure of non-CF HBE cells to airway secretions isolated from CF lungs, namely, sterile supernatants of mucopurulent material (SMM), also caused enhanced IL-8 secretion and increased ATP release. The SMM-induced increase in ATP release was sensitive to Ca21 chelation and vesicle trafficking/exocytosis inhibitors, but not to pannexin inhibition. Transcript levels of the vesicular nucleotide transporter, but not pannexin 1, were up-regulated after SMM exposure. SMM- treated cultures displayed increased basal mucin secretion, but mu- cin secretion was not enhanced in response to hypotonic challenge after the exposure of cells to either vehicle or SMM. We propose that CF airway inflammation up-regulates the capacity of airway epithelia to release ATP via Ca21-dependent vesicular mechanisms not asso- ciated with mucin granule secretion.