Document Detail


Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner.
MedLine Citation:
PMID:  19641187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
24660837 - Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated...
2675117 - Chloroquine and acid vesicle function.
19958387 - Cultural conditions required for the induction of an adaptive acid-tolerance response (...
19302267 - Na+/h+ exchangers and rhoa regulate acidic extracellular ph-induced lysosome traffickin...
395627 - Effect of orally administered 15(r)-15-methyl prostaglandin e2 and/or an anticholinergi...
10757727 - Three new triterpenoids from peganum nigellastrum.
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    
Affiliation:
Cincinnati Children's Hospital Medical Center, OH, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acids / pharmacology*
Animals
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
Female
Hydrogen-Ion Concentration
Male
Mice
Mice, Inbred BALB C
Mice, Transgenic
Pneumonia / complications,  genetics,  metabolism,  pathology
Protons
Receptors, G-Protein-Coupled / genetics,  metabolism,  physiology*
Grant Support
ID/Acronym/Agency:
R21A1079251//PHS HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Acids; 0/GPCR25 protein, mouse; 0/Protons; 0/Receptors, G-Protein-Coupled; 60-92-4/Cyclic AMP
Comments/Corrections

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


Previous Document:  Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell ly...
Next Document:  Epigenetic mechanisms of regulation of Foxp3 expression.