Document Detail

Inflammation promotes airway epithelial ATP release via calcium-dependent vesicular pathways.
MedLine Citation:
PMID:  23763446     Owner:  NLM     Status:  MEDLINE    
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 Ca(2+) 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 mucin 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 Ca(2+)-dependent vesicular mechanisms not associated with mucin granule secretion.
Seiko F Okada; Carla M P Ribeiro; Juliana I Sesma; Lucia Seminario-Vidal; Lubna H Abdullah; Catharina van Heusden; Eduardo R Lazarowski; Richard C Boucher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  49     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-04     Completed Date:  2013-12-27     Revised Date:  2014-11-04    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  814-20     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphate / metabolism*
Calcium Signaling* / drug effects
Cell Size
Cells, Cultured
Chelating Agents / pharmacology
Connexins / metabolism
Cystic Fibrosis / immunology,  metabolism*
Epithelial Cells / drug effects,  immunology,  metabolism*
Inflammation Mediators / metabolism
Interleukin-8 / metabolism
Mucins / metabolism
Mucociliary Clearance
Nerve Tissue Proteins / metabolism
Nucleotide Transport Proteins / metabolism
Osmotic Pressure
Pneumonia / immunology,  metabolism*
Primary Cell Culture
Respiratory Mucosa / drug effects,  immunology,  metabolism*
Secretory Vesicles / drug effects,  immunology,  metabolism*
Time Factors
Grant Support
Reg. No./Substance:
0/Chelating Agents; 0/Connexins; 0/IL8 protein, human; 0/Inflammation Mediators; 0/Interleukin-8; 0/Mucins; 0/Nerve Tissue Proteins; 0/Nucleotide Transport Proteins; 0/PANX1 protein, human; 8L70Q75FXE/Adenosine Triphosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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