Stimulated neutrophils from patients with autosomal recessive chronic granulomatous disease fail to phosphorylate a Mr-44,000 protein (original) (raw)

Nature volume 316, pages 547–549 (1985)Cite this article

Abstract

Phagocytosing neutrophils, monocytes, macrophages and eosino-phils produce a burst of non-mitochondrial respiration that is important for the killing and digestion of microbes. Much of the information about the oxidase system involved comes from studies on patients with chronic granulomatous disease (CGD), a syndrome in which an undue predisposition to infection results from complete absence of this burst of stimulated respiratory activity1. The basis of the oxidase activity is an electron transport chain, the only established component of which is a very unusual _b_-type cyto-chrome (_b_−245) (ref. 2). The molecular defect in the X-linked subgroup of CGD is the absence of this cytochrome _b_−245, which, however, appears to be normal in those subjects with the autosomal recessive mode of inheritance3. In an attempt to identify an abnormality of activation, or an absence or malfunction of a proximal component of the electron transport chain in this latter group, we examined protein phosphorylation in neutrophils after activation of the oxidase with phorbol myristate acetate. All four of the patients studied demonstrated a selective lack of the enhanced phosphorylation of a protein of relative molecular mass (_M_r) 44,000 (44K) that was observed in normal subjects and in two CGD patients with an X-linked inheritance. This molecule, therefore, could be an important functional component of the oxidase.

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References

  1. Holmes, B., Page, A. R. & Good, R. A. J. clin. Invest. 46, 1422–1432 (1967).
    Article CAS Google Scholar
  2. Segal, A. W. & Jones, O. T. G. Nature 276, 515–517 (1978).
    Article ADS CAS Google Scholar
  3. Segal, A. W. et al. New Engl. J. Med. 308, 245–251 (1983).
    Article CAS Google Scholar
  4. Nishizuka, Y. Nature 308, 693–698 (1984).
    Article ADS CAS Google Scholar
  5. Schneider, C., Zanetti, M. & Romeo, D. FEBS Lett. 127, 4–8 (1981).
    Article CAS Google Scholar
  6. Andrews, P. C. & Babior, B. M. Blood 61, 333–340 (1983).
    Article CAS Google Scholar
  7. Andrews, P. C. & Babior, B. M. Blood 64, 883–890 (1984).
    Article CAS Google Scholar
  8. Segal, A. W. & Jones, O. T. G. Biochem. J. 182, 181–188 (1979).
    Article CAS Google Scholar
  9. Segal, A. W., Dorling, J. & Coade, S. J Cell Biol. 85, 42–59 (1980).
    Article CAS Google Scholar
  10. Hitzig, W. H. & Seger, R. A. Hum. Genet. 64, 207–215 (1983).
    Article CAS Google Scholar
  11. Segal, A. W. & Jones, O. T. G. FEBS Lett. 110, 111–114 (1980).
    Article CAS Google Scholar
  12. Cagan, R. H. & Karnovsky, M. L. Nature 204, 255–257 (1964).
    Article ADS CAS Google Scholar
  13. Gabig, T. G. & Babior, B. M. J. biol Chem. 254, 9070–9074 (1979).
    CAS PubMed Google Scholar
  14. Badwey, J. A. & Karnovsky, M. L. A. Rev. Biochem. 49, 695–726 (1980).
    Article CAS Google Scholar
  15. Light, D. R., Walsh, C., O'Callaghan, A. M., Goetzel, E. J. & Tauber, A. I. Biochemistry 20, 1468–1476 (1981).
    Article CAS Google Scholar
  16. Cross, A. R., Jones, O. T. G., Garcia, R. & Segal, A. W. Biochem. J. 208, 759–763 (1982).
    Article CAS Google Scholar
  17. Packard, B. Trends biochem. Sci. 10, 138 (1985).
    Article Google Scholar
  18. Cockroft, S. Biochim. biophys. Acta 794, 37–46 (1984).
    Article Google Scholar
  19. Laemmli, U. K. Nature 227, 680–685 (1970).
    Article ADS CAS Google Scholar

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Authors and Affiliations

  1. Department of Haematology, Faculty of Clinical Sciences, University College London, London, WC1E 6HX, UK
    Anthony W. Segal & Paul G. Heyworth
  2. Department of Experimental Pathology, Faculty of Clinical Sciences, University College London, London, WC1E 6HX, UK
    Shamshad Cockcroft & Margaret M. Barrowman

Authors

  1. Anthony W. Segal
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  2. Paul G. Heyworth
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  3. Shamshad Cockcroft
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  4. Margaret M. Barrowman
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Segal, A., Heyworth, P., Cockcroft, S. et al. Stimulated neutrophils from patients with autosomal recessive chronic granulomatous disease fail to phosphorylate a _M_r-44,000 protein.Nature 316, 547–549 (1985). https://doi.org/10.1038/316547a0

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