A novel H+ conductance in eosinophils: Unique characteristics and absence in chronic granulomatous disease

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

Research output: Article

116 Citations (Scopus)

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 Zn2+ 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.

Original languageEnglish
Pages (from-to)183-194
Number of pages12
JournalJournal of Experimental Medicine
Volume190
Issue number2
DOIs
Publication statusPublished - júl. 19 1999

Fingerprint

Chronic Granulomatous Disease
NADPH Oxidase
Eosinophils
Diethyl Pyrocarbonate
Cytochromes
Phagocytes
Histidine
Protons
Ions
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

A novel H+ conductance in eosinophils : Unique characteristics and absence in chronic granulomatous disease. / Bánfi, Botond; Schrenzel, Jacques; Nüsse, Oliver; Lew, Daniel P.; Ligeti, E.; Krause, Karl Heinz; Demaurex, Nicolas.

In: Journal of Experimental Medicine, Vol. 190, No. 2, 19.07.1999, p. 183-194.

Research output: Article

Bánfi, Botond ; Schrenzel, Jacques ; Nüsse, Oliver ; Lew, Daniel P. ; Ligeti, E. ; Krause, Karl Heinz ; Demaurex, Nicolas. / A novel H+ conductance in eosinophils : Unique characteristics and absence in chronic granulomatous disease. In: Journal of Experimental Medicine. 1999 ; Vol. 190, No. 2. pp. 183-194.
@article{3c1eee1eb8f44241a6696d96d538598e,
title = "A novel H+ conductance in eosinophils: Unique characteristics and absence in chronic granulomatous disease",
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 Zn2+ 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 = "Eosinophils, Granulomatous disease, Hydrogen ion concentration, NADPH oxidase, Proton conductance",
author = "Botond B{\'a}nfi and Jacques Schrenzel and Oliver N{\"u}sse and Lew, {Daniel P.} and E. Ligeti and Krause, {Karl Heinz} and Nicolas Demaurex",
year = "1999",
month = "7",
day = "19",
doi = "10.1084/jem.190.2.183",
language = "English",
volume = "190",
pages = "183--194",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - A novel H+ conductance in eosinophils

T2 - Unique characteristics and absence in chronic granulomatous disease

AU - Bánfi, Botond

AU - Schrenzel, Jacques

AU - Nüsse, Oliver

AU - Lew, Daniel P.

AU - Ligeti, E.

AU - Krause, Karl Heinz

AU - Demaurex, Nicolas

PY - 1999/7/19

Y1 - 1999/7/19

N2 - 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 Zn2+ 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.

AB - 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 Zn2+ 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.

KW - Eosinophils

KW - Granulomatous disease

KW - Hydrogen ion concentration

KW - NADPH oxidase

KW - Proton conductance

UR - http://www.scopus.com/inward/record.url?scp=0039102450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0039102450&partnerID=8YFLogxK

U2 - 10.1084/jem.190.2.183

DO - 10.1084/jem.190.2.183

M3 - Article

C2 - 10432282

AN - SCOPUS:0039102450

VL - 190

SP - 183

EP - 194

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 2

ER -