Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels (original) (raw)

Nature volume 310, pages 691–693 (1984)Cite this article

Abstract

It has long been assumed that a rise in cytosolic free Ca2+, [Ca2+]i, is a necessary and sufficient event for the stimulation of a variety of cellular processes1,2. The development of a technique which allows monitoring of [Ca2+]i in small intact cells3 has led to a critical revision of this simple postulate4–7. We have recently shown that in neutrophils, Ca2+-ionophore-induced elevations of [Ca2+]i, quantitatively similar to those caused by chemotatic peptides, are ineffective in stimulating cell responses8, which suggests that an additional signal is required for receptor-mediated activation. Here we show that subthreshold concentrations of phorbol myristate acetate (PMA) and of a Ca2+ ionophore can quantitatively mimic the effect of a physiological agonist. However, PMA at higher concentrations can trigger NADPH-oxidase activity, exocytosis and protein phosphorylation, even when [Ca2+]i is lowered 10–20 times below the normal resting level. These results strongly suggest that activation of protein kinase C is sufficient, by itself, to induce NADPH-oxidase activation and exocytosis of secondary granules in neutrophils.

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References

  1. Rubin, R. P. Calcium and Cellular Secretion (Plenum, New York, 1982).
    Book Google Scholar
  2. Gomperts, B. D. in Biological Membranes Vol. 5 (ed. Chapman, D.) 284–340 (Academic, New York, 1984).
    Google Scholar
  3. Tsien, R. Y., Pozzan, T. & Rink, T. J., J. Cell Biol. 94, 325–334 (1982).
    Article CAS PubMed Google Scholar
  4. Rink, T. J., Smith, S. W. & Tsien, R. Y. FEBS Lett. 148, 21–26 (1982).
    Article CAS PubMed Google Scholar
  5. Rink, T. J., Sanchez, A. & Hallam, I. J. Nature 305, 317–319 (1983).
    Article ADS CAS PubMed Google Scholar
  6. Pozzan, T., Arslan, P., Tsien, R. Y. & Rink, T. J. J. Cell Biol. 94, 335–340 (1982).
    Article CAS PubMed Google Scholar
  7. Meldolesi, J., Huttner, W. B., Tsien, R. Y. & Pozzan, T. Proc. natn. Acad. Sci. U.S.A. 81, 620–624 (1984).
    Article ADS CAS Google Scholar
  8. Pozzan, T., Lew, D. P., Wollheim, C. B. & Tsien, R. Y. Science 221, 1413–1415 (1983).
    Article ADS CAS PubMed Google Scholar
  9. Nishizuka, Y. Trends biochem. Sci. 8, 13–16 (1981).
    Article Google Scholar
  10. Kajikawa, N. et al. Biochem. biophys. Res. Commun. 116, 743–750 (1983).
    Article CAS PubMed Google Scholar
  11. Kaibuchi, K. et al. J. biol. Chem. 258, 6701–6704 (1983).
    CAS PubMed Google Scholar
  12. Michell, R. Trends biochem. Sci. 8, 263–265 (1983).
    Article CAS Google Scholar
  13. Yin, H. L. & Stossel, T. P. J. biol. Chem. 255, 9490–9493 (1980).
    CAS PubMed Google Scholar
  14. Klee, C. B., Crouch, T. H. & Krinks, M. H. Proc. natn. Acad. Sci. U.S.A. 76, 6270–6273 (1979).
    Article ADS CAS Google Scholar
  15. Pershandsingh, H. A., Landt, M. & McDonald, J. M. J. biol. Chem. 255, 8983–8986 (1980).
    Google Scholar
  16. Niggli, V., Adunyah, E. S. & Carafoli, E. J. biol. Chem. 256, 8588–8592 (1981).
    CAS PubMed Google Scholar
  17. Gillis, J. M., Thomason, D., Lefevre, J. & Kretsinger, R. H. J. Muscle Res. Cell Motility 3, 377–398 (1982).
    Article CAS Google Scholar
  18. Burger, D., Stein, E. A. & Cox, J. A. J. biol. Chem. 258, 14733–14739 (1983).
    CAS PubMed Google Scholar
  19. Castagna, M. et al. J. biol. Chem. 257, 7847–7851 (1982).
    CAS PubMed Google Scholar
  20. Schneider, C., Zanetti, M. & Romeo, D. FEBS Lett. 127, 4–8 (1981).
    Article CAS PubMed Google Scholar
  21. Lew, D. P. & Stossel, T. P. J. clin. Invest. 67, 1–9 (1981).
    Article CAS PubMed PubMed Central Google Scholar
  22. Estensen, R. D., White, J. G. & Holmes, B. Nature 248, 347–348 (1974).
    Article ADS CAS PubMed Google Scholar
  23. Gunther, G. R. J. biol. Chem. 256, 12040–12045 (1981).
    CAS PubMed Google Scholar
  24. Niedel, J. E., Kuhn, L. J. & Vandenbark, G. R. Proc. natn. Acad. Sci. U.S.A. 8, 263–265 (1983).
    Google Scholar
  25. Sando, J. J. et al. Fedn Proc. 42, 2250–2253 (1983).
    Google Scholar
  26. Helfman, D. M., Appelbaum, B. D., Vogler, W. R. & Kuo, J. F. Biochem. biophys. Res. Commun. 111, 847–853 (1983).
    Article CAS PubMed Google Scholar

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Authors and Affiliations

  1. CNR Unit for the Study of Physiology of Mitochondria, c/o Institute of General Pathology, Via Loredan 16, 35100, Padova, Italy
    F. Di Virgilio & T. Pozzan
  2. Infectious Diseases Unit, Department of Internal Medicine, University of Geneva, CH-1211, Geneva, 4, Switzerland
    D. P. Lew

Authors

  1. F. Di Virgilio
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  2. D. P. Lew
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  3. T. Pozzan
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Di Virgilio, F., Lew, D. & Pozzan, T. Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels.Nature 310, 691–693 (1984). https://doi.org/10.1038/310691a0

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