A Novel H+ Conductance in Eosinophils: Unique Characteristics and Absence in Chronic Granulomatous Disease

Botond Bánfi; Jacques Schrenzel; Oliver Nüsse; Daniel P. Lew; Erzsébet Ligeti; Karl-Heinz Krause; Nicolas Demaurex

doi:10.1084/jem.190.2.183

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A Novel H+ Conductance in Eosinophils: Unique Characteristics and Absence in Chronic Granulomatous Disease

Journal article

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A Novel H+ Conductance in Eosinophils: Unique Characteristics and Absence in Chronic Granulomatous Disease

Botond Bánfi, Jacques Schrenzel, Oliver Nüsse, Daniel P. Lew, Erzsébet Ligeti, Karl-Heinz Krause and Nicolas Demaurex

The Journal of experimental medicine, Vol.190(2), pp.183-194

07/19/1999

DOI: 10.1084/jem.190.2.183

PMCID: PMC2195580

PMID: 10432282

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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 ∼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.

eosinophils

granulomatous disease

hydrogen ion concentration

NADPH oxidase

Original

proton conductance

Details

Title: Subtitle: A Novel H+ Conductance in Eosinophils: Unique Characteristics and Absence in Chronic Granulomatous Disease
Creators: Botond Bánfi - Division of Infectious Diseases, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland.
Jacques Schrenzel - From the Division of Infectious Diseases, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland
Oliver Nüsse - From the Division of Infectious Diseases, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland
Daniel P. Lew - From the Division of Infectious Diseases, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland
Erzsébet Ligeti - Semmelweis University
Karl-Heinz Krause - From the Department of Geriatrics, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland
Nicolas Demaurex - University of Geneva
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.190(2), pp.183-194
DOI: 10.1084/jem.190.2.183
PMID: 10432282
PMCID: PMC2195580
NLM abbreviation: J Exp Med
ISSN: 0022-1007
eISSN: 1540-9538
Publisher: The Rockefeller University Press
Language: English
Date published: 07/19/1999
Academic Unit: Anatomy and Cell Biology; Otolaryngology; Internal Medicine
Record Identifier: 9984284336902771

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