Document Detail

Coupled nucleotide and mucin hypersecretion from goblet-cell metaplastic human airway epithelium.
MedLine Citation:
PMID:  20935191     Owner:  NLM     Status:  MEDLINE    
Adenosine triphosphate (ATP) and its metabolite adenosine regulate airway mucociliary clearance via activation of purinoceptors. In this study, we investigated the contribution of goblet cells to airway epithelial ATP release. Primary human bronchial epithelial (HBE) cultures, typically dominated by ciliated cells, were induced to develop goblet cell metaplasia by infection with respiratory syncytial virus (RSV) or treatment with IL-13. Under resting conditions, goblet-cell metaplastic cultures displayed enhanced mucin secretion accompanied by increased rates of ATP release and mucosal surface adenosine accumulation as compared with nonmetaplastic control HBE cultures. Intracellular calcium chelation [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester] or disruption of the secretory pathways (nocodazole, brefeldin A, and N-ethylmaleimide) decreased mucin secretion and ATP release in goblet-cell metaplastic HBE cultures. Conversely, stimuli that triggered calcium-regulated mucin secretion (e.g., ionomycin or UTP) increased luminal ATP release and adenyl purine accumulation in control and goblet-cell metaplastic HBE cultures. Goblet cell-associated ATP release was not blocked by the connexin/pannexin hemichannel inhibitor carbenoxolone, suggesting direct nucleotide release from goblet cell vesicles rather than the hemichannel insertion. Collectively, our data demonstrate that nucleotide release is increased by goblet cell metaplasia, reflecting, at least in part, a mechanism tightly associated with goblet cell mucin secretion. Increased goblet cell nucleotide release and resultant adenosine accumulation provide compensatory mechanisms to hydrate mucins by paracrine stimulation of ciliated cell ion and water secretion and maintain mucociliary clearance, and to modulate inflammatory responses.
Seiko F Okada; Liqun Zhang; Silvia M Kreda; Lubna H Abdullah; C William Davis; Raymond J Pickles; Eduardo R Lazarowski; Richard C Boucher
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-08
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  45     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-04     Completed Date:  2011-10-03     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-60     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphate / metabolism*
Blotting, Western
Bronchi / cytology,  drug effects,  metabolism*,  virology
Calcium / metabolism
Cells, Cultured
Egtazic Acid / analogs & derivatives,  pharmacology
Enzyme-Linked Immunosorbent Assay
Epithelium / drug effects,  metabolism*,  virology
Ethylmaleimide / pharmacology
Goblet Cells / pathology*,  secretion*,  virology
Immunoenzyme Techniques
Interleukin-13 / pharmacology
Metaplasia / metabolism*,  pathology,  virology
Mucins / secretion*
RNA, Messenger / genetics
Receptors, Purinergic P2Y2 / metabolism
Respiratory Syncytial Virus Infections / metabolism,  virology
Respiratory Syncytial Viruses / pathogenicity
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Interleukin-13; 0/Mucins; 0/RNA, Messenger; 0/Receptors, Purinergic P2Y2; 526U7A2651/Egtazic Acid; 8L70Q75FXE/Adenosine Triphosphate; K22DDW77C0/1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; O3C74ACM9V/Ethylmaleimide; SY7Q814VUP/Calcium

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