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

Banfi, Botond; Schrenzel, Jacques; Nusse, Olivier; Lew, Daniel Pablo; Ligeti, E.; Krause, Karl-Heinz; Demaurex, Nicolas

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Title		A novel H(+) conductance in eosinophils: unique characteristics and absence in chronic granulomatous disease
Authors		Banfi, Botond Schrenzel, Jacques Nusse, Olivier Lew, Daniel Pablo Ligeti, E. Krause, Karl-Heinz Demaurex, Nicolas
Published in		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		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
Identifiers		PMID: 10432282
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195580/pdf/98-2226.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Citation (ISO format)		BANFI, Botond et al. A novel H(+) conductance in eosinophils: unique characteristics and absence in chronic granulomatous disease. In: Journal of Experimental Medicine, 1999, vol. 190, n° 2, p. 183-194. https://archive-ouverte.unige.ch/unige:7091