Document Detail


Detrimental role of the airway mucin Muc5ac during ventilator-induced lung injury.
MedLine Citation:
PMID:  23187315     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute lung injury (ALI) is associated with high morbidity and mortality in critically ill patients. At present, the functional contribution of airway mucins to ALI is unknown. We hypothesized that excessive mucus production could be detrimental during lung injury. Initial transcriptional profiling of airway mucins revealed a selective and robust induction of MUC5AC upon cyclic mechanical stretch exposure of pulmonary epithelia (Calu-3). Additional studies confirmed time- and stretch-dose-dependent induction of MUC5AC transcript or protein during cyclic mechanical stretch exposure in vitro or during ventilator-induced lung injury in vivo. Patients suffering from ALI showed a 58-fold increase in MUC5AC protein in their bronchoalveolar lavage. Studies of the MUC5AC promoter implicated nuclear factor κB in Muc5ac induction during ALI. Moreover, mice with gene-targeted deletion of Muc5ac⁻/⁻ experience attenuated lung inflammation and pulmonary edema during injurious ventilation. We observed that neutrophil trafficking into the lungs of Muc5ac⁻/⁻ mice was selectively attenuated. This implicates that endogenous Muc5ac production enhances pulmonary neutrophil trafficking during lung injury. Together, these studies reveal a detrimental role for endogenous Muc5ac production during ALI and suggest pharmacological strategies to dampen mucin production in the treatment of lung injury.
Authors:
M Koeppen; E N McNamee; K S Brodsky; C M Aherne; M Faigle; G P Downey; S P Colgan; C M Evans; D A Schwartz; H K Eltzschig
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-28
Journal Detail:
Title:  Mucosal immunology     Volume:  6     ISSN:  1935-3456     ISO Abbreviation:  Mucosal Immunol     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-17     Completed Date:  2014-01-16     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  101299742     Medline TA:  Mucosal Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  762-75     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemotaxis, Leukocyte / genetics,  immunology
Disease Models, Animal
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation
Humans
Mice
Mice, Knockout
Mucin 5AC / genetics*,  metabolism*
NF-kappa B / metabolism
Neutrophil Infiltration / genetics,  immunology
Neutrophils / immunology,  metabolism
Pneumonia / genetics,  immunology,  metabolism
Respiratory Mucosa / immunology,  metabolism
Stress, Mechanical
Transcription, Genetic
Transendothelial and Transepithelial Migration / genetics,  immunology
Ventilator-Induced Lung Injury / genetics*,  immunology,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 DK083385/DK/NIDDK NIH HHS; R01 HL090669/HL/NHLBI NIH HHS; R01 HL092188/HL/NHLBI NIH HHS; R01 HL098294/HL/NHLBI NIH HHS; R01-DK083385/DK/NIDDK NIH HHS; R01-HL0921/HL/NHLBI NIH HHS; R01HL098294/HL/NHLBI NIH HHS; R37 DK050189/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Mucin 5AC; 0/NF-kappa B
Comments/Corrections

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


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