| Coupled nucleotide and mucin hypersecretion from goblet-cell metaplastic human airway epithelium. | |
| | |
MedLine Citation:
|
PMID: 20935191 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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: 2013-03-28 |
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 |
Affiliation:
|
Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 27599, USA. seiko_okada@med.unc.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
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 Exocytosis Goblet Cells / pathology*, secretion*, virology Humans 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 | |
ID/Acronym/Agency:
|
P01 HL034322-25/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Interleukin-13; 0/Mucins; 0/RNA, Messenger; 0/Receptors, Purinergic P2Y2; 128-53-0/Ethylmaleimide; 56-65-5/Adenosine Triphosphate; 67-42-5/Egtazic Acid; 7440-70-2/Calcium; K22DDW77C0/1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Carbonylation caused by cigarette smoke extract is associated with defective macrophage immunity.
Next Document: Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection.