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NADPH oxidase is not required for spontaneous and Staphylococcus aureus-induced apoptosis of monocytes

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Abstract

Reactive oxygen intermediates (ROI) generated in the respiratory burst reaction are crucial for the killing of bacteria and fungi in phagocytes. The key enzyme for the respiratory burst reaction is the NADPH oxidase. Reactive oxygen intermediates have additionally been proposed to be of general importance for the expression of FAS and soluble FAS ligand (sFASL) and the subsequent induction of apoptosis. This conclusion has been drawn from the observation that neutrophils with an inborn lack of the NADPH oxidase as well as cell lines and monocytes with artificially blocked NADPH oxidase exhibit impaired apoptosis. Being one of the few centers caring for patients with chronic granulomatous disease (CGD) who exhibit an inborn lack of NADPH oxidase, we had the unique opportunity to determine the role of the NADPH oxidase for apoptosis in monocytes with otherwise unmanipulated cells of these patients (CGD monocytes). We compared the expression of FAS on monocytes and the concentration of sFASL in the supernatant between CGD monocytes and healthy donors undergoing spontaneous apoptosis. Neither the expression of FAS nor the concentration of sFASL was decreased in CGD monocytes. We further compared spontaneous apoptosis and apoptosis occurring after the phagocytosis of Staphylococcus aureus in CGD monocytes to monocytes of healthy controls. In these experiments we could not determine any significant impairment of apoptosis in CGD monocytes. Our data indicate for the first time that in an unmanipulated human model a functional NADPH oxidase is not crucial for the apoptosis of monocytes and disprove a general role of ROI for the induction of apoptosis in phagocytes.

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Abbreviations

CGD:

Chronic granulomatous disease

DHR:

Dihydrorhodamine

DPI:

Diphenyliodonium

ROI:

Reactive oxygen intermediates

sFASL:

Soluble FAS ligand

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Acknowledgements

This work was supported by a grant of the CGD Research Trust, UK to HvB, JR, and ARW, by a grant of the Sächsische Staatsministerium für Wissenschaft und Kunst, Germany to ARW, and by a grant of the Medical Faculty Dresden, Germany to HvB. We thank M. Ernst, Research Center Borstel, for critical discussions. We thank P. Burger, Miltenyi Biotec, for helpful technical suggestions. We thank K. Navratiel and M. Rösler for technical assistance.

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Authors and Affiliations

  1. Laboratory for Clinical Research, University Hospital Carl Gustav Carus, Fetscherstr. 74, 01309, Dresden, Germany

    H. v. Bernuth, C. Kulka, J. Roesler & A. Rösen-Wolff

  2. Outpatient Clinic for Immunodeficiencies, Department of Pediatrics, University Hospital Carl Gustav Carus, Dresden, Germany

    H. v. Bernuth, J. Roesler & M. Gahr

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  1. H. v. Bernuth
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  2. C. Kulka
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  3. J. Roesler
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  4. M. Gahr
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  5. A. Rösen-Wolff
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Correspondence to H. v. Bernuth.

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v. Bernuth, H., Kulka, C., Roesler, J. et al. NADPH oxidase is not required for spontaneous and Staphylococcus aureus-induced apoptosis of monocytes. Ann Hematol 83, 206–211 (2004). https://doi.org/10.1007/s00277-003-0837-4

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  • DOI: https://doi.org/10.1007/s00277-003-0837-4

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