Scientific article

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

Published inThe Journal of experimental medicine, vol. 190, no. 2, p. 183-194
Publication date1999

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.

  • Adult
  • Child
  • Electron Transport
  • Enzyme Activation
  • Eosinophils/ metabolism
  • Female
  • Granulomatous Disease, Chronic/genetics/ metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Male
  • Membrane Glycoproteins/deficiency/genetics
  • Membrane Potentials
  • NADPH Oxidase/deficiency/genetics
  • Phosphoproteins/deficiency/genetics
  • Respiratory Burst
Citation (ISO format)
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.
Updates (1)
ISSN of the journal0022-1007

Technical informations

Creation06/21/2010 10:23:10 AM
First validation06/21/2010 10:23:10 AM
Update time03/14/2023 3:42:42 PM
Status update03/14/2023 3:42:42 PM
Last indexation08/28/2023 6:10:49 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack