Abstract
We investigated the influence of neopterin and 7,8-dihydroneopterin on the myeloperoxidase activity and secretory degranulation in neutrophils and interaction of pteridines with its major substrate (hydrogen peroxide) and intermediate product of halogenation cycle (hypochlorous acid). It was shown that, in neutrophils, the redox-pair, neopterin and 7,8-dihydroneopterin, control oxygen activation, which is regulated by myeloperoxidase. Pteridines influence the secretion of myeloperoxidase depending on concentration and decrease the level of hydrogen peroxide and hypochlorous acid, which are the substrate and intermediate product of the enzyme, respectively. It was found that, in micromolar concentrations, 7,8-dihydroneopterin is a noncompetitive inhibitor of myeloperoxidase. We suppose that myeloperoxidase facilitates 7,8-dihydroneopterin oxidation by hypochlorous acid and results in an increase in neopterin concentration. These changes modify the concentration of intracellular and extracellular reactive oxygen species.
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Abbreviations
- ROS:
-
reactive oxygen species
- INFγ:
-
interferon γ
- LCL:
-
luminol dependent chemiluminescence
- MP:
-
myeloperoxidase
References
Boyum, A., Isolation of Lymphocytes, Granulocytes and Macrophages, Scand. J. Immunol., 1976, vol. 5, pp. 9–15.
Gamalei, I.A. and Klyubin, I.V., Hydrogen Peroxide as a Signal Molecule, Tsitologiia, 1996, vol. 38, no. 1, pp. 1233–1247.
Hampton, M.B., Kettle, A.J., and Winterbourn, C.C., Inside the Neutrophil Phagosome: Oxidants, Myeloperoxidase, and Bacterial Killing, Blood, 1998, vol. 92, no. 9, pp. 3007–3017.
Hofmann, B., Neopterin and Human Immunodeficiency Virus Infection, Eur. J. Clin. Chem. Clin. Biochem., 1993, vol. 31, pp. 191–195.
Huber, C., Batchelor, J.R., Fuchs, D., Hausen, A., Lang, A., Niederwieser, D., Reibnegger, G., Swetly, P., Troppmair, J., and Wachter, H., Immune Response-Associated Production of Neopterin Release from Macrophages Primarily under Control of Interferon-Gamma, J. Exp. Med., 1984, vol. 160, pp. 310–316.
Kavalenka, A.I., Semenkova, G.N., Cherenkevich, S.N., Smirnova, E.N., and Gerein, V., Systems of Reactive Oxygen Species Generation in Human Neutrophils: Chemiluminescent Analysis, Clin. Lab., 2003, vol. 49, p. 566.
Kojima, S., Icho, T., Kajiwara, Y., and Kubota, K., Neopterin as an Endogenous Antioxidant, FEBS Lett., 1992, vol. 304, pp. 163–166.
Kovalenko, E.I., Semenkova, G.N., and Cherenkevich, S.N., Effect of Hydrogen Peroxide on Ability of Neutrophils to Generate the Reactive Oxygen and Chlorine Species and Secrete Myeloperoxidase in Vitro, Tsitologiya, 2007, vol. 49. no. 10, pp. 839–847.
McNally, J.A. and Bell, A,L., Myeloperoxidase-Based Chemiluminescence of Polymorphonuclear Leukocytes and Monocytes, J. Bio. Chemilum., 1996, vol. 11, pp. 99–106.
Oettl, K., Dikalov, S., Freisleben, H.J., Mlekusch, W., and Reibnegger, G., Spin Trapping Study of Antioxidant Properties of Neopterin and 7,8-Dihydroneopterin, Biochem. Biophys. Res. Commun., 1997, vol. 234, pp. 774–778.
Oettl, K., Greilbergera, J., Dikalovb, S., and Reibnegger, G., Interference of 7,8-Dihydroneopterin with Peroxynitrite-Mediated Reactions, Biochem. Biophys. Res. Commun., 2004, vol. 321, pp. 379–385.
Razumovitch, J.A., Fuchs, D., Semenkova, G.N., and Cherenkevich, S.N., Influence of Neopterin on Generation of Reactive Species by Myelopexidase in Human Neutrophils, Biochim., Biophys., Acta., 2004, vol. 1672, pp. 46–50.
Razumovitch, J.A., Semenkova, G.N., Fuchs, D., and Cherenkevich, S.N., Influence of Neopterin on the Generation of Reactive Oxygen Species in Human Neutrophils, FEBS Letters, 2003, vol. 549, pp. 83–86.
Schobersberger, W., Hoffmann, G., Hobisch-Hagen, P., Bock, G., Volk, H., Baier-Bitterlich, G., Wirleitner, B., Wachter, H., and Fuchs, D., Neopterin and 7,8-Dihydroneopterin Induce Apoptosis in the Rat Alveolar Epithelial Cell Line L2, FEBS Letters, 1996, vol. 397, pp. 263–268.
Semenkova, G.N., Novikova, T.M., Chrenkevich, S.N., and Drapeza, A.I., Chemiluminescence in the Peroxidase Oxidation of Luminol with Hydrogen Peroxide in Various Media, Lab. delo, 1991, vol. 11, pp. 13–16.
Timoshenko, A.V., Kayser, K., Drings, P., Andre, S., Dong, X., Kaltner, H., Schneller, M., and Gabius, H.J., Carbohydrate-Binding Proteins (Plant/Human Lectins and Autoantibodies from Human Serum) as Mediators of Release of Lysozyme, Elastase, and Myeloperoxidase from Human Neutrophils, Res. Exper. Med., 1995, vol. 195, pp. 153–162.
Vetohin, C.C., Semenkova, G.N., and Cherenkevich, S.N., Chemiluminescent Methods of Analysis of the Cells Activation Processes, in Luminescent Analysis in Medicine and Biological Investigations, Riga: All Union Meeting, 1987 pp. 81–85.
Werner, E.R., Bichler, A., Daxenbichler, G., Fuchs, D., Fuith, L.C., Hausen, A., Hetzel, H., Reibnegger, G., and Wachter, H., Determination of Neopterin in Serum and Urine, Clin Chem., 1987, vol. 33, pp. 62–66.
Widner, B., Baier-Bitterlich, G., Wede, I., Wirleitner, B., and Fuchs, D., Neopterin Derivatives Modulate the Nitration of Tyrosine by Peroxynitrite, Biochem. Biophys. Res. Commun., 1998, vol. 248, pp. 341–346.
Widner, B., Mayr, C., Wirleitner, B., and Fuchs, D., Oxidation of 7,8-Dihydroneopterin by Hypochlorous Acid Yields Neopterin, Biochem. Biophys. Res. Commun., 2000, vol. 275, pp. 307–311.
Widner, B., Wirleitner, B., Baier-Bitterlich, G., Weis, G., and Fuchs, D., Cellular Immune Activation, Neopterin Production, Tryptophan Degradation and the Development of Immunodeficiency, Archivum Immunol. Ther. Exp., 2000, vol. 48, pp. 251–258.
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Original Russian Text © M.G. Petukh, G.N. Semenkova, D. Fuchs, S.N. Cherenkevich, 2009, published in Tsitologiya, Vol. 51, No. 10, 2009, pp. 824–829.
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Petukh, M.G., Semenkova, G.N., Fuchs, D. et al. Pteridine-dependent oxygen activation in neutrophils. Cell Tiss. Biol. 3, 538–543 (2009). https://doi.org/10.1134/S1990519X09060066
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DOI: https://doi.org/10.1134/S1990519X09060066