title: Proton channel HVCN1 is required for effector functions of mouse eosinophils.
abstract: BACKGROUND
  Proton currents are required for optimal respiratory burst in phagocytes. Recently, HVCN1 was identified as the molecule required for the voltage-gated proton channel activity associated with the respiratory burst in neutrophils. Although there are similarities between eosinophils and neutrophils regarding their mechanism for respiratory burst, the role of proton channels in eosinophil functions has not been fully understood.
  
  
  RESULTS
  In the present study, we first identified the expression of the proton channel HVCN1 in mouse eosinophils. Furthermore, using HVCN1-deficient eosinophils, we demonstrated important cell-specific effector functions for HVCN1. Similar to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils produced significantly less reactive oxygen species (ROS) upon phorbol myristate acetate (PMA) stimulation compared with WT eosinophils. In contrast to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils did not show impaired calcium mobilization or migration ability compared with wild-type (WT) cells. Uniquely, HVCN1-deficient eosinophils underwent significantly increased cell death induced by PMA stimulation compared with WT eosinophils. The increased cell death was dependent on NADPH oxidase activation, and correlated with the failure of HVCN1-deficient cells to maintain membrane polarization and intracellular pH in the physiological range upon activation.
  
  
  CONCLUSIONS
  Eosinophils require proton channel HVCN1 for optimal ROS generation and prevention of activation-induced cell death.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhu
authors.forename: Eucabeth
authors.initials: E
authors.lastname: Mose
authors.forename: Nives
authors.initials: N
authors.lastname: Zimmermann
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000143:Acids; C540876:Hv1 proton channel, mouse; D007473:Ion Channels; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium