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Effect of deuterium oxide on neutrophil oxidative metabolism, phagocytosis, and lysosomal enzyme release


We have previously shown that deuterium oxide (D2O) enhances the oxidation of methionine, a myeloperoxidase (MPO)-mediated reaction, by human neutrophils during phagocytosis. However, D2O has no effect on the oxidation of methionine by the purified MPO-H2O2-Cl system. To explain this observation, we studied the effect of D2O on the oxidative metabolism, phagocytosis, and lysosomal enzyme release by human neutrophils. D2O stimulated the hexose monophosphate shunt (HMS) activity of resting neutrophils in a dose-response fashion. In the presence of latex particles or phorbol myristate acetate (PMA), D2O brought about an exaggerated stimulation of the HMS activity. This enhancement of the HMS activity by D2O was markedly reduced when neutrophils form two patients with X-linked chronic granulomatous disease (CGD) were used, either in the presence or absence of latex particles or PMA. Superoxide and H2O2 production by neutrophils in the presence of latex particles or PMA were also stimulated by D2O. In contrast, D2O inhibited the ingestion of latex particles. D2O enhanced the extracellular release of MPO, but not lactate dehydrogenase, by neutrophils only in the simultaneous presence of cytochalasin B and latex particles. The enhancement of HMS activity and MPO release by D2O was partially inhibited by colchicine. Our results suggest that enhancement of neutrophil oxidative metabolism by D2O may in part explain the stimulation of methionine oxidation by phagocytosing neutrophils.

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  1. 1.

    Kritchevsky, D. 1960. Deuterium isotope effects in chemistry and biology.Ann. N. Y. Acad. Sci. 84:573–781.

  2. 2.

    Kajiwara, T., andD. R. Kearn. 1973. Direct spectroscopic evidence for a deuterium solvent effect on the lifetime of singlet oxygen in water.J. Am. Chem, Soc. 95:5866–5890.

  3. 3.

    Foote, C. S. 1976. Photosensitized oxidation and singlet oxygen: Consequences in biological systems.In Free Radicals in Biology, Vol. 2. William A. Pryor, editor. Academic Press, New York. 85–133.

  4. 4.

    Marsland, D., L. G. Tilney, andM. Hirshfield. 1971. Stabilizing effects of D2O on the microtubular components and needle-like form of heliozoan axopods—a pressure-temperature analysis.J. Cell. Physiol. 77:187–193.

  5. 5.

    Gillespie, E., andL. M. Lichtenstein. 1972. Heavy water enhances IgE-mediated histamine release from human leukocytes: Evidence for microtubule involvement.Proc. Soc. Exp. Biol. Med. 140:1228–1234.

  6. 6.

    Stock, C., J. F. Launay, J. F. Grenier, andH. Bauduin. 1978. Pancreatic acinar cell changes induced by caerulein, vinblastine, deuterium oxide, and cytochalasin B in vitro.Lab. Invest. 38:157–164.

  7. 7.

    Nakamura, M., A. Nakagawara, andS. Minakami. 1976. Mimicking of phagocytic metabolism by leukocytes suspended in heavy water (D2O).Exp. Cell. Res. 102:429–431.

  8. 8.

    Zurier, R. B., G. Weissmann, S. Hoffstein, S. Kammehman, andH. H. Tai. 1974. Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomie agonists, and agents which affect microtubule function.J. Clin. Invest. 53:299–309.

  9. 9.

    Tsan, M. F., andJ. W. Chen. 1980. Oxidation of methionine by human polymorphonuclear leukocytes.J. Clin. Invest. 65:1041–1050.

  10. 10.

    Tsan, M. F. 1982. Myeloperoxidase-mediated oxidation of methionine.J. Cell. Physiol. 111:49–54.

  11. 11.

    Tsan, M. F., andP. A. McIntyre. 1975. Stimulation by propylthiouracil of the hexose monophosphate shunt in human polymorphonuclear leukocytes during phagocytosis.Br. J. Haematol. 31:193–208.

  12. 12.

    Tsan, M. F., K. H. Douglass, andP. A. McIntyre. 1977. Hydrogen peroxide production and killing ofStaphylococcus aureus by human polymorphonuclear leukocytes.Blood 49:437–444.

  13. 13.

    Babior, B. M., R. S. Kipnes, andJ. T. Curnutte. 1973. Biological defense mechanism: The production by leukocytes of superoxide, a potential bactericidal agent.J. Clin. Invest. 52:741–744.

  14. 14.

    Glasoe, P. K., andF. A. Long. 1960. Use of glass electrodes to measure acidities in deuterium oxide.J. Physiol. Chem. 24:188–190.

  15. 15.

    Roberts, J., andJ. H. Quastel. 1963. Particle uptake by polymorphonuclear leukocytes and Ehrlich ascites carcinoma cells.Biochem. J. 89:150–156.

  16. 16.

    Michell, R. H., M. J. Karnovsky, andM. L. Karnovsky. 1970. The distribution of some granule-associated enzymes in guinea pig polymorphonuclear leukocytes.Biochem. J. 166:207–216.

  17. 17.

    Bergmeyer, H. C. L., andE. Bernt. 1974. Lactate Dehydrogenase. UV assay with pyruvate and NADH.In Methods of Enzymatic Analysis, Vol. 2. H. U. Bergmeyer, editor. Academic Press, New York. 574–576.

  18. 18.

    Croxton, F. E. 1953. Elementary Statistics with Applications in Medicine and The Biological Sciences. Dover Publications, New York. 235–244.

  19. 19.

    Gabig, T. G., R. S. Kipnes, andB. M. Babior. 1978. Solubilizatoin of the O 2 -forming activity responsible for the respiratory burst in human neutrophils.J. Biol. Chem. 253: 6663–6665.

  20. 20.

    Goldstein, I. M., M. Cerquiera, S. Lind, andH. Kaplan. 1977. Evidence that the superoxide generating system of human granulocytes (PMN) is associated with the cell surface.J. Clin. Invest. 59:249–254.

  21. 21.

    Root, R. K., andJ. A. Metcalf. 1977. H2O2 release from human granulocytes during phagocytosis. Relationship to superoxide anion formation and cellular metabolism of H2O2. Studies with normal and cytochalasin B-treated cells.J. Clin. Invest. 60:1266–1279.

  22. 22.

    Inoue, S., andH. Sato. 1967. Cell motility by labile association of molecules. The nature of mitotic spindle fibers and their role in chromosome movement.J. Gen. Physiol. 50:259–288.

  23. 23.

    Raminer, B., andJ. Kimura. 1972. Deuterium oxide: Inhibition of calcium release in muscle.Science 176:406–407.

  24. 24.

    Schimmel, R. 1975. Deuterium oxide stimulates glucose metabolism and inhibits lipolysis in rat epididymal adipose tissue.Biochem. Biophys. Res. Commun. 64:347–354.

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Correspondence to Rita M. Turkall.

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Tsan, M.-., Turkall, R.M. Effect of deuterium oxide on neutrophil oxidative metabolism, phagocytosis, and lysosomal enzyme release. Inflammation 6, 387–396 (1982).

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  • Methionine
  • Colchicine
  • Cytochalasin
  • Human Neutrophil
  • Phorbol Myristate Acetate