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A novel H(+) conductance in eosinophils: unique characteristics and absence in chronic granulomatous disease

Ligeti, E.
Published in The Journal of experimental medicine. 1999, vol. 190, no. 2, p. 183-194
Abstract Efficient mechanisms of H(+) ion extrusion are crucial for normal NADPH oxidase function. However, whether the NADPH oxidase-in analogy with mitochondrial cytochromes-has an inherent H(+) channel activity remains uncertain: electrophysiological studies did not find altered H(+) currents in cells from patients with chronic granulomatous disease (CGD), challenging earlier reports in intact cells. In this study, we describe the presence of two different types of H(+) currents in human eosinophils. The "classical" H(+) current had properties similar to previously described H(+) conductances and was present in CGD cells. In contrast, the "novel" type of H(+) current had not been described previously and displayed unique properties: (a) it was absent in cells from gp91- or p47-deficient CGD patients; (b) it was only observed under experimental conditions that allowed NADPH oxidase activation; (c) because of its low threshold of voltage activation, it allowed proton influx and cytosolic acidification; (d) it activated faster and deactivated with slower and distinct kinetics than the classical H(+) currents; and (e) it was approximately 20-fold more sensitive to Zn(2+) and was blocked by the histidine-reactive agent, diethylpyrocarbonate (DEPC). In summary, our results demonstrate that the NADPH oxidase or a closely associated protein provides a novel type of H(+) conductance during phagocyte activation. The unique properties of this conductance suggest that its physiological function is not restricted to H(+) extrusion and repolarization, but might include depolarization, pH-dependent signal termination, and determination of the phagosomal pH set point.
Keywords AdultChildElectron TransportEnzyme ActivationEosinophils/ metabolismFemaleGranulomatous Disease, Chronic/genetics/ metabolismHumansHydrogen-Ion ConcentrationKineticsMaleMembrane Glycoproteins/deficiency/geneticsMembrane PotentialsNADPH Oxidase/deficiency/geneticsPhosphoproteins/deficiency/geneticsRespiratory Burst
PMID: 10432282
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BANFI, Botond et al. A novel H(+) conductance in eosinophils: unique characteristics and absence in chronic granulomatous disease. In: The Journal of experimental medicine, 1999, vol. 190, n° 2, p. 183-194. https://archive-ouverte.unige.ch/unige:7091

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Deposited on : 2010-06-21

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