Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner

• Published in: Blood Vol. 114; no. 13; pp. 2774 - 2782
• Main Authors: Kottyan, Leah C., Collier, Ann R., Cao, Khanh H., Niese, Kathryn A., Hedgebeth, Megan, Radu, Caius G., Witte, Owen N., Khurana Hershey, Gurjit K., Rothenberg, Marc E., Zimmermann, Nives
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 24.09.2009; Americain Society of Hematology; American Society of Hematology
• Series: Phagocytes, Granulocytes, and Myelopoiesis
• Subjects: Acids - pharmacology; Animals; Apoptosis - drug effects; Apoptosis - genetics; Asthma - complications; Asthma - genetics; Asthma - metabolism; Asthma - pathology; Biological and medical sciences; Cell Survival - drug effects; Cell Survival - genetics; Cells, Cultured; Cyclic AMP - metabolism; Cyclic AMP - physiology; Disease Models, Animal; Eosinophils - drug effects; Eosinophils - metabolism; Eosinophils - physiology; Female; Hematologic and hematopoietic diseases; Hydrogen-Ion Concentration; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Transgenic; Phagocytes, Granulocytes, and Myelopoiesis; Pneumonia - complications; Pneumonia - genetics; Pneumonia - metabolism; Pneumonia - pathology; Protons; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, G-Protein-Coupled - physiology; Cyclic AMP; pH; Hematology; Viability; Eosinophil; Granulocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-05-220681

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.