Advertisement

Bulletin of Experimental Biology and Medicine

, Volume 161, Issue 4, pp 495–500 | Cite as

Myeloperoxidase Stimulates Neutrophil Degranulation

  • D. V. Grigorieva
  • I. V. Gorudko
  • A. V. Sokolov
  • V. A. Kostevich
  • V. B. Vasilyev
  • S. N. Cherenkevich
  • O. M. PanasenkoEmail author
Article

Myeloperoxidase, heme enzyme of azurophilic granules in neutrophils, is released into the extracellular space in the inflammation foci. In neutrophils, it stimulates a dose-dependent release of lactoferrin (a protein of specific granules), lysozyme (a protein of specific and azurophilic granules), and elastase (a protein of azurophilic granules). 4-Aminobenzoic acid hydrazide, a potent inhibitor of peroxidase activity of myeloperoxidase, produced no effect on neutrophil degranulation. Using signal transduction inhibitors (genistein, methoxyverapamil, wortmannin, and NiCl2), we demonstrated that myeloperoxidase-induced degranulation of neutrophils resulted from enzyme interaction with the plasma membrane and depends on activation of tyrosine kinases, phosphatidylinositol 3-kinases (PI3K), and calcium signaling. Myeloperoxidase modified by oxidative/halogenation stress (chlorinated and monomeric forms of the enzyme) lost the potency to activate neutrophil degranulation.

Key Words

human neutrophils neutrophil degranulation myeloperoxidase signaling systems oxidative/halogenation stress 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gorudko IV, Cherenkevich SN, Tcherkalina OS, Sokolov AV, Pulina MO, Zakharova ET, Vasilyev VB, Panasenko OM. New approaches to the measurement of the concentration and peroxidase activity of myeloperoxidase in human blood plasma. Rus. J. Bioorganic Chem. 2009:35(5):566-575.CrossRefGoogle Scholar
  2. 2.
    Grigorieva DV, Gorudko IV, Sokolov AV, Shamova EV, Vasiliev VB, Panasenko OM, Cherenkevich SN. Regulation of Ca2+-signaling in neutrophils by myeloperoxidase. Doklady NAN Belarusi. 2014:58(4):55-60. Russian.Google Scholar
  3. 3.
    Panasenko OM, Gorudko OM, Sokolov AV. Hypochloric acid as free radical precursor in living systems. Uspekhi Biol. Khimii. 2013:53:195-244. Russian.Google Scholar
  4. 4.
    Amulic B, Cazalet C, Hayes GL, Metzler K.D, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu. Rev. Immunol. 2012:30:459-489.CrossRefPubMedGoogle Scholar
  5. 5.
    Baldus S, Eiserich JP, Mani A, Castro L, Figueroa M, Chumley P, Ma W, Tousson A, White CR, Bullard DC, Brennan ML, Lusis AJ, Moore KP, Freeman BA. Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration. J.Clin. Invest. 2001:108(12):1759-1770.Google Scholar
  6. 6.
    Coles B, Bloodsworth A, Clark SR, Lewis MJ, Cross AR, Freeman BA, O’Donnell VB. Nitrolinoleate inhibits superoxide generation, degranulation, and integrin expression by human neutrophils: novel antiinflammatory properties of nitric oxide-derived reactive species in vascular cells. Circ. Res. 2002:91(5):375-381.CrossRefPubMedGoogle Scholar
  7. 7.
    Davies MJ, Hawkins CL, Pattison DI, Rees MD. Mammalian heme peroxidases: from molecular mechanisms to health implications. Antioxid. Redox Signal. 2008:10(7):1199-1222.CrossRefPubMedGoogle Scholar
  8. 8.
    El Kebir D, József L, Pan W, Filep JG. Myeloperoxidase delays neutrophil apoptosis through CD11b/CD18 integrins and prolongs inflammation. Circ. Res. 2008:103(4):352-359.CrossRefPubMedGoogle Scholar
  9. 9.
    Gorudko IV, Sokolov AV, Shamova EV, Grudinina NA, Drozd ES, Shishlo LM, Grigorieva DV, Bushuk SB, Bushuk BA, Chizhik SA, Cherenkevich SN, Vasilyev VB, Panasenko OM. Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry. Biol. Open. 2013:2(9):916-923.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Klinke A, Nussbaum C, Kubala L, Friedrichs K, Rudolph TK, Rudolph V, Paust HJ, Schröder C, Benten D, Lau D, Szocs K, Furtmüller PG, Heeringa P, Sydow K, Duchstein HJ, Ehmke H, Schumacher U, Meinertz T, Sperandio M, Baldus S. Mye-loperoxidase attracts neutrophils by physical forces. Blood. 2011:117(4):1350-1358.CrossRefPubMedGoogle Scholar
  11. 11.
    Lacy P. Mechanisms of Degranulation in Neutrophils. Allergy Asthma Clin. Immunol. 2006:2(3):98-108.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Lau D, Mollnau H, Eiserich JP, Freeman BA, Daiber A, Gehling UM, Brümmer J, Rudolph V, Münzel T, Heitzer T, Meinertz T, Baldus S. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc. Natl Acad. Sci. USA. 2005:102(2):431-436.CrossRefPubMedGoogle Scholar
  13. 13.
    Paumann-Page M, Furtmüller PG, Hofbauer S, Paton LN, Obinger C, Kettle AJ. Inactivation of human myeloperoxidase by hydrogen peroxide. Arch. Biochem. Biophys. 2013:539(1):51-62.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Timoshenko AV, Kayser K, Gabius HJ. Lectin-triggered superoxide/H2O2 and granule enzyme release from cells. Methods in Molecular Medicine. Vol. 9: Lectin Methods and Protocols, Rhodes JM, Milton JD, eds. Totowa, 1997. pp. 441-451.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • D. V. Grigorieva
    • 1
  • I. V. Gorudko
    • 1
  • A. V. Sokolov
    • 2
    • 3
  • V. A. Kostevich
    • 2
    • 3
  • V. B. Vasilyev
    • 2
  • S. N. Cherenkevich
    • 1
  • O. M. Panasenko
    • 3
    Email author
  1. 1.Physics Faculty, Belarusian State UniversityMinskBelarus
  2. 2.Institute of Experimental MedicineSt. PetersburgRussia
  3. 3.Scientific Research Institute of Physical-Chemical MedicineRussian Federal Medical-Biological AgencyMoscowRussia

Personalised recommendations