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Electron currents generated by the human phagocyte NADPH oxidase

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Abstract

Electron transport across biological membranes is a well-known feature of bacteria, mitochondria and chloroplasts, where it provides motive forces for vectorial transport processes1. In contrast, electron transport is generally not found in the plasma membrane of eukaryotic cells, possibly because it would interfere with electric processes at the plasma membrane. An exception is provided by the phagocyte NADPH oxidase, which generates superoxide (

) through electron transfer from cytosolic NADPH to extracellular oxygen2,3,4,5. The enzyme is essential for host defence, and patients with chronic granulomatous disease, who lack the functional enzyme, suffer from severe infections6,7. It has been suggested that electron transfer by the NADPH oxidase might be electrogenic8. Here we demonstrate, using the whole-cell patch-clamp technique, the generation of electron currents by the NADPH oxidase in human eosinophil granulocytes. The currents were absent in granulocytes of sufferers of chronic granulomatous disease and under conditions of low oxygen. Generation of electron currents across the plasma membrane of eukaryotic cells has not been observed previously and might be — independently of the generation of superoxide — a physiologically relevant function of the phagocyte NADPH oxidase.

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Figure 1: Inward currents associated with activation of NADPH oxidase in human eosinophils.
Figure 2: Activation of NADPH-oxidase currents by cytosolic [Ca2+], receptor agonists, and phorbol esters.
Figure 3: Currents in eosinophils from patients with genetic defects.
Figure 4: Noise analysis and voltage-dependence of the NADPH oxidase currents.

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Acknowledgements

We thank E. Huggler for technical assistance; L. Bernheim, S. Rawlings, and M. Rossier for discussions; W. Zimmerli, R. Seger and P. Beris for help with the patients; and N. Mensi for the G6PD determination. This work was supported by grants from the Swiss National Foundation (to J.S., K.-H.K., N.D., B.B.), the Janggen Poehn Foundation (J.S.), the Max Cloetta Foundation (N.D.), FEBS (B.B.), and the Swedish Medical Research Grant (L.S.).

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  1. Jacques Schrenzel

    Present address: Division of Clinical Microbiology, Mayo Clinic, Rochester, 200 First Street SW, Minnesota, 55905, USA

Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, University Hospital, 1211, Geneva, 4, Switzerland

    Jacques Schrenzel, Lena Serrander, Botond Bánfi, Oliver Nüße, Reyhaneh Fouyouzi, Daniel P. Lew & Karl-Heinz Krause

  2. Department of Physiology, University Medical Center, 1211, Geneva, 4, Switzerland

    Nicolas Demaurex

  3. Department of Physiology, Semmelweis Medical University, H-1444 Budapest 8, PO Box 259, Hungary

    Botond Bánfi

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  1. Jacques Schrenzel
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  2. Lena Serrander
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  5. Reyhaneh Fouyouzi
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  6. Daniel P. Lew
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  8. Karl-Heinz Krause
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Correspondence to Karl-Heinz Krause.

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Schrenzel, J., Serrander, L., Bánfi, B. et al. Electron currents generated by the human phagocyte NADPH oxidase. Nature 392, 734–737 (1998). https://doi.org/10.1038/33725

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