Document Detail

Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner.
MedLine Citation:
PMID:  19641187     Owner:  NLM     Status:  MEDLINE    
The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5'-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase-dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65(-/-) mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner.
Leah C Kottyan; Ann R Collier; Khanh H Cao; Kathryn A Niese; Megan Hedgebeth; Caius G Radu; Owen N Witte; Gurjit K Khurana Hershey; Marc E Rothenberg; Nives Zimmermann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-07-29
Journal Detail:
Title:  Blood     Volume:  114     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-25     Completed Date:  2009-10-27     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2774-82     Citation Subset:  AIM; IM    
Cincinnati Children's Hospital Medical Center, OH, USA.
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MeSH Terms
Acids / pharmacology*
Apoptosis / drug effects,  genetics
Asthma / complications,  genetics,  metabolism,  pathology
Cell Survival / drug effects,  genetics
Cells, Cultured
Cyclic AMP / metabolism,  physiology*
Disease Models, Animal
Eosinophils / drug effects*,  metabolism,  physiology
Hydrogen-Ion Concentration
Mice, Inbred BALB C
Mice, Transgenic
Pneumonia / complications,  genetics,  metabolism,  pathology
Receptors, G-Protein-Coupled / genetics,  metabolism,  physiology*
Grant Support
R21A1079251//PHS HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Acids; 0/GPCR25 protein, mouse; 0/Protons; 0/Receptors, G-Protein-Coupled; 60-92-4/Cyclic AMP

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