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Electron currents generated by the human phagocyte NADPH oxidase

Nature volume 392, pages 734–737 (1998)Cite this article

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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References

  1. Mitchell, P. Foundations of vectorial metabolism and osmochemistry. Biosci. Rep. 11, 297–346 (1991).

    Article  CAS  Google Scholar 

  2. Klebanoff, S. J. Oxygen metabolism and the toxic properties of phagocytes. Ann. Intern. Med. 93, 480–489 (1980).

    Article  CAS  Google Scholar 

  3. Clark, R. A. The human neutrophil respiratory burst oxidase. J. Infect. Dis. 161, 1140–1147 (1990).

    Article  CAS  Google Scholar 

  4. Segal, A. W. & Abo, A. The biochemical basis of the NADPH oxidase of phagocytes. Trends Biochem. Sci. 18, 43–47 (1993).

    Article  CAS  Google Scholar 

  5. Chanock, S. J., el Benna, J., Smith, R. M. & Babior, B. M. The respiratory burst oxidase. J. Biol. Chem. 269, 24519–24522 (1994).

    CAS  PubMed  Google Scholar 

  6. Clark, R. A. Genetic variation in chronic granulomatous disease. Hosp. Pract. 25, 51–55 (1990).

    Article  CAS  Google Scholar 

  7. Boxer, L. A. & Blackwood, R. A. Leukocyte disorders: quantitative and qualitative disorders of the neutrophil, part 1. Pediatr. Rev. 17, 19–28 (1996).

    Article  CAS  Google Scholar 

  8. Henderson, L. M., Chappell, J. B. & Jones, O. T. The superoxide-generating NADPH oxidase of human neutrophils is electrogenic and associated with a H+ channel. Biochem. J. 246, 325–329 (1987).

    Article  CAS  Google Scholar 

  9. Shult, P. A., Graziano, F. M., Wallow, I. H. & Busse, W. W. Comparison of superoxide generation and luminol-dependent chemiluminescence with eosinophils and neutrophils from normal individuals. J. Lab. Clin. Med. 106, 638–645 (1985).

    CAS  PubMed  Google Scholar 

  10. Gallin, E. K. & McKinney, L. C. in Current Topics in Membranes and Transport. Vol. 35: Mechanisms of Leukocyte Activation (eds Kleinzeller, A., Grinstein, S. & Rotstein, O. D.) 127–152 (Academic, San Diego, 1990).

    Google Scholar 

  11. Nanda, A. & Grinstein, S. The membrane potential of resting and activated neutrophils: determinants and significance. Cell Physiol. Biochem. 1, 65–75 (1991).

    Article  Google Scholar 

  12. Demaurex, N., Schrenzel, J., Jaconi, M. E., Lew, D. P. & Krause, K.-H. Proton channels, plasma membrane potential, and respiratory burst in human neutrophils. Eur. J. Haematol. 51, 309–312 (1993).

    Article  CAS  Google Scholar 

  13. Newburger, P. E. et al. Parental diagnosis of chronic granulomatous disease. N. Engl. J. Med. 300, 178–181 (1979).

    Article  CAS  Google Scholar 

  14. Cross, A. R. & Jones, O. T. The effect of the inhibitor diphenylene iodonium on the superoxide-generating system of neutrophils. Specific labelling of a component polypeptide of the oxidase. Biochem. J. 237, 111–116 (1986).

    Article  CAS  Google Scholar 

  15. Schrenzel, J., Lew, D. P. & Krause, K. H. Proton currents in human eosinophils. Am. J. Physiol. Cell Physiol. 271, C1861–C1871 (1996).

    Article  CAS  Google Scholar 

  16. Vives Corrons, J. L. et al. Severe-glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with chronic hemolytic anemia, granulocyte dysfunction, and increased susceptibility to infections: description of a new molecular variant (G6PD Barcelona). Blood 59, 428–434 (1982).

    CAS  PubMed  Google Scholar 

  17. Benesch, R. E. & Benesch, R. Enzymatic removal of oxygen for polarography and related methods. Science 118, 447–448 (1953).

    Article  ADS  CAS  Google Scholar 

  18. Hille, B. Ionic Channels of Excitable Membranes (Sinauer Associates, Sunderland, MA, 1992).

    Google Scholar 

  19. Gordienko, D. V. et al. Voltage-activated proton current in eosinophils from human blood. J. Physiol. 496, 299–316 (1996).

    Article  CAS  Google Scholar 

  20. Cherny, V. V., Markin, V. S. & De Coursey, T. E. The voltage-activated hydrogen ion conductance in a rat alveolar epithelial cells is determined by the pH gradient. J. Gen. Physiol. 105, 861–896 (1995).

    Article  CAS  Google Scholar 

  21. Saier, M. H. Peter Mitchell and his chemiosmotic theories. ASM News 63, 13–21 (1997).

    Google Scholar 

  22. Zimmerli, W., Lew, D. P., Suter, S., Wyss, M. & Waldvogel, F. A. In vitro efficacy of several antibiotics against intracellular S. aureus in chronic granulomatous disease. Helv. Paediatr. Acta 38, 51–61 (1983).

    CAS  PubMed  Google Scholar 

  23. Varnai, P. et al. Highly cooperative Ca2+ activation of intermediate conductance K+ channels in HL-60 granulocytes. J. Physiol. (Lond.) 472, 373–390 (1993).

    Article  CAS  Google Scholar 

  24. Demaurex, N. et al. Regulation Ca2+ influx in myeloid cells: role of plasma membrane potential, inositol phosphates, cytosolic free [Ca2+], and filling state of intracellular Ca2+ stores. J. Clin. Invest. 90, 830–839 (1992).

    Article  CAS  Google Scholar 

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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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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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