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VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification

Okochi, Yoshifumi
Sasaki, Mari
Okamura, Yasushi
Published in The Journal of experimental medicine. 2010, vol. 207, no. 1, p. 129-139
Abstract Neutrophils kill microbes with reactive oxygen species generated by the NADPH oxidase, an enzyme which moves electrons across membranes. Voltage-gated proton channels (voltage-sensing domain only protein [VSOP]/Hv1) are required for high-level superoxide production by phagocytes, but the mechanism of this effect is not established. We show that neutrophils from VSOP/Hv1-/- mice lack proton currents but have normal electron currents, indicating that these cells have a fully functional oxidase that cannot conduct protons. VSOP/Hv1-/- neutrophils had a more acidic cytosol, were more depolarized, and produced less superoxide and hydrogen peroxide than neutrophils from wild-type mice. Hydrogen peroxide production was rescued by providing an artificial conductance with gramicidin. Loss of VSOP/Hv1 also aborted calcium responses to chemoattractants, increased neutrophil spreading, and decreased neutrophil migration. The migration defect was restored by the addition of a calcium ionophore. Our findings indicate that proton channels extrude the acid and compensate the charge generated by the oxidase, thereby sustaining calcium entry signals that control the adhesion and motility of neutrophils. Loss of proton channels thus aborts superoxide production and causes a severe signaling defect in neutrophils.
Keywords AnimalsAnti-Bacterial Agents/pharmacologyCalcium/*metabolismCell Adhesion/drug effects/physiologyCell Movement/drug effects/*physiologyCell Polarity/drug effects/*physiologyCytosol/metabolismElectron Transport/drug effects/physiologyGramicidin/pharmacologyHydrogen Peroxide/metabolismIon Channels/genetics/*metabolismIon Transport/drug effects/physiologyIonophores/pharmacologyMiceNADPH Oxidase/genetics/metabolismNeutrophils/*metabolismSignal Transduction/drug effects/*physiologySuperoxides/metabolism
PMID: 20026664
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Research group Signaux intracellulaires (210)
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CHEMALY, Antoine et al. VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification. In: The Journal of experimental medicine, 2010, vol. 207, n° 1, p. 129-139. doi: 10.1084/jem.20091837 https://archive-ouverte.unige.ch/unige:20921

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Deposited on : 2012-05-23

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