Skip to main content
SpringerLink
Log in

Study on Myeloperoxidase Role in Antituberculous Defense in the Context of Cytokine Activation

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Myeloperoxidase (MPO), next to the NO synthase2 (NOS2), and NADPH oxidase, is the key enzyme of the oxidative burst responsible for the antimicrobial immunity. Because MPO participates in the eradication of Mycobacterium tuberculosis in the in vitro model and the extracellular enzyme may activate cells to cytokine synthesis, we investigated the changes in the enzyme concentration in serum of patients with active pulmonary tuberculosis (TB) and correlations between MPO and TNF-α, IFN-γ, and IL-12. To our knowledge, our study is the first to indicate the involvement of MPO during active TB which manifested itself in the significant increase in serum concentration. The statistically significant elevation of TNF-α and IL-12 was also noticed in serum of the TB positive group. The statistical analysis revealed no correlation between the cytokine and MPO production in the studied cases. However, the increase in TNF-α and IL-12 serum concentration with simultaneous elevation of serum MPO in the group of the highest enzyme concentration may imply that correlation between the enzyme and the cytokines should not be excluded. Our study suggests possible involvement of MPO in the antituberculous, immunological response, and implies its connection with TNF-α and IL-12 activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ottenhoff, T. H. M., E. Spierings, P. H. Nibbering, R. De Jong, and R. R. P. De Vries. 1997. Modulation of protective and pathological immunity in mycobacterial infections. Int. Arch. Allergy Immunol. 113:400-408.

    Google Scholar 

  2. Silva, C. L., V. L. D. Bonato, K. M. Lima, A. A. M Coelho-Castelo, L. H. Faccioli, A. Sartori, A. O. De Souza, and S. C. Leão. 2001. Cytotoxic T cells and mycobacteria. FEMS Microbiol. Lett. 197:11-18.

    Google Scholar 

  3. Ruan, J., G. S. John, S. Ehrt, L. Riley, and C. Nathan. 1999. noxR3, a novel gene from Mycobacterium tuberculosis, protects Salmonella typhimurium from nitrosative and oxidative stress. Infect. Immun. 67:3276-3283.

    Google Scholar 

  4. Firmani, M. A. and L. W. Riley. 2002. Reactive nitrogen intermediates have a bacteriostatic effect on Mycobacterium tuberculosis in vitro. J. Clin. Microbiol. 40:3162-3166.

    Google Scholar 

  5. May, M. E. and P. J. Spagnuolo. 1987. Evidence for activation of a respiratory burst in the interaction of human neutrophils with Mycobacterium tuberculosis. Infect. Immun. 55:2304-2307.

    Google Scholar 

  6. Bogdan, C., M. Röllinghoff, and A. Diefenbach. 2000. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr. Opin. Immunol. 12:64-76.

    Google Scholar 

  7. Ismail, N., J. P. Olano, H. Feng, and D. H. Walker. 2002. Current status of immune mechanisms of killing of intracellular microorganisms. FEMS Microbiol. Lett. 207:111-120.

    Google Scholar 

  8. Winterbourn, C. C., M. C. Vissers, and A. J. Kettle. 2000. Myeloperoxidase. Curr. Opin. Hematol. 7:53-58.

    Google Scholar 

  9. Burner, U., P. G. Furtmüller, A. J. Kettle, W. H. Koppenol, and C. Obinger. 2000. Mechanism of reaction of myeloperoxidase with nitrite. J. Biol. Chem. 275:20597-20601.

    Google Scholar 

  10. Klebanoff, S. J. 1999. Myeloperoxidase. Proc. Assoc. Am. Physicians 111:383-389.

    Google Scholar 

  11. Van Dalen, C. J., C. C. Winterbourn, R. Senthilmohan, and A. J. Kettle. 2000. Nitrite as a substrate and inhibitor of myeloperoxidase. Implications for nitration and hypochlorous acid production at sites of inflammation. J. Biol. Chem. 275:11638-11644.

    Google Scholar 

  12. Winterbourn, C. C. and A. J. Kettle. 2000. Biomarkers of myeloperoxidase-derived hypochlorous acid. Free Radic. Biol. Med. 29:403-409.

    Google Scholar 

  13. Whiteman, M., D. C. Hooper, G. S. Scott, H. Koprowski, and B. Halliwell. 2002. Inhibition of hypochlorous acid-induced cellular toxicity by nitrite. Proc. Natl. Acad. Sci. U.S.A. 99:12061-12066.

    Google Scholar 

  14. Grattendick, K., R. Stuart, E. Roberts, J. Lincoln, S. S. Lefkowitz, A. Bollen, N. Moguilevsky, H. Friedman, and D. L. Lefkowitz. 2002. Alveolar macrophage activation by myeloperoxidase. A model for exacerbation of lung inflammation. Am. J. Respir. Cell Mol. Biol. 26:716-722.

    Google Scholar 

  15. Fenton, M. J., M. W. Vermeulen, S. Kim, M. Burdick, R. M. Strieter, and H. Kornfeld. 1997. Induction of gamma interferon production in human alveolar macrophages by Mycobacterium tuberculosis. Infect. Immun. 65:5149-5156.

    Google Scholar 

  16. MacMicking, J., Q. Xie, and C. Nathan. 1997. Nitric oxide and macrophage function. Annu. Rev. Immunol. 15:323-350.

    Google Scholar 

  17. MacMicking, J. D., R. J. North, R. LaCourse, J. S. Mudgett, S. K. Shah, and C. F. Nathan. 1997. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 94:5243-5248.

    Google Scholar 

  18. Klebanoff, S. J., R. M. Locksley, E. C. Jong, and H. Rosen. 1983. Oxidative response of phagocytes to parasite invasion. Ciba. Found. Symp. 99:92-112.

    Google Scholar 

  19. Manca, C., S. Paul, C. E. BarryIII, V. H. Freedman, and G. Kaplan. 1999. Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro. Infect. Immun. 67:74-79.

    Google Scholar 

  20. Borelli, V., E. Banfi, M. G. Perrotta, and G. Zabucchi. 1999. Myeloperoxidase exerts microbicidal activity against Mycobacterium tuberculosis. Infect. Immun. 67:4149-4152.

    Google Scholar 

  21. Kettle, A. J. and C. C. Winterbourn. 1992. Oxidation of hydroquinone by myeloperoxidase. Mechanism of stimulation by benzoquinone. J. Biol. Chem. 267:8319-8324.

    Google Scholar 

  22. Orme, I. M. and A. M. Cooper. 1999. Cytokine/chemokine cascades in immunity to tuberculosis. Immunol. Today 20:307-312.

    Google Scholar 

  23. Modlin, R. L. and P. F. Barnes. 1995. IL12 and the human immune response to mycobacteria. Res. Immunol. 146:526-531.

    Google Scholar 

  24. Flynn, J. L. and J. D. Ernst. 2000. Immune responses in tuberculosis. Curr. Opin. Immunol. 12:432-436.

    Google Scholar 

  25. De Jong, R., F. Altare, I. Haagen, D. G. Elferink, T. De Boer, V. Van Breda, J. C. Peter, P. J. Kabel, J. M. T. Draaisma, J. T. van Dissel, F. P. Kroon, J. Casanova, and T. H. M. Ottenhoff. 1998. Severe mycobacterial and salmonella infections in interleukin-12 receptor-deficient patients. Science 280:1435-1438.

    Google Scholar 

  26. Wang, J., J. Wakeham, R. Harkness, and Z. Xing. 1999. Macrophages are a significant source of type 1 cytokines during mycobacterial infection. J. Clin. Invest. 103:1023-1029.

    Google Scholar 

  27. Vanham, G., Z. Toossi, C. S. Hirsch, R. S. Wallis, S. K. Schwander, E. A. Rich, and J. J. Ellner. 1997. Examining a paradox in the pathogenesis of human pulmonary tuberculosis:Immune activation and suppression/anergy. Tuber. Lung Dis. 78:145-58.

    Google Scholar 

  28. Kawaguchi, H., Y. Ina, S. Ito, S. Sato, Y. Sugiura, H. Tomita, N. Ogisu, K. Takada, M. Yamamoto, M. Morishita, and K. Yoshikawa. 1996. Serum levels of soluble tumor necrosis factor (TNF)receptors in patients with pulmonary tuberculosis. Kekkaku 71:259-265.

    Google Scholar 

  29. Verbon, A., N. Juffermans, S. J. Van Deventer, P. Speelman, H. Van Deutekom, and T. Van Der Poll. 1999. Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment. Clin. Exp. Immunol. 115:110-113.

    Google Scholar 

  30. Knoring, B. E., A. S. Simbirtsev, I. Sakharova, A. Kotov, N. V. Pisareva, and T. B. Resnianskaia. 1998. Production of cytokines in different forms of pulmonary tuberculosis. Probl. Tuberk. 3:67-71.

    Google Scholar 

  31. Altare, F., A. Durandy, D. Lammas, J. F. Emile, S. Lamhamedi, F. Le Deist, P. Drysdale, E. Jouanguy, R. Doffinger, F. Bernaudin, O. Jeppsson, J. A. Gollob, E. Meinl, A. W. Segal, A. Fischer, D. Kumararatne, and J. L. Casanova. 1998. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280:1432-1435.

    Google Scholar 

  32. Lefkowitz, D. L., C. K. Mills, N. Moguilevsky, A. Bollen, A. Vaz, and S. S. Lefkowitz. 1993. Regulation of macrophage function by human recombinant myeloperoxidase. Immunol. Lett. 36:43-49.

    Google Scholar 

  33. Srivastava, C. H., T. A. Rado, D. Bauerle, and H. E. Broxmeyer. 1991. Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-±. J. Immunol. 146:1014-1019.

    Google Scholar 

  34. Kawano, S., E. Tatsumi, N. Yoneda, S. Nagata, and N. Yamaguchi. 1993. Suppression of gene expression of myeloperoxidase (MPO) by gamma-interferon (IFN-gamma) in HL60 cells. Lymphokine Cytokine Res. 12:81-85.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Microbiology Department, Medical University, Lublin, Poland

    M. Koziol-Montewka, A. Kolodziejek & J. Oles

Authors
  1. M. Koziol-Montewka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Kolodziejek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Oles
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Koziol-Montewka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koziol-Montewka, M., Kolodziejek, A. & Oles, J. Study on Myeloperoxidase Role in Antituberculous Defense in the Context of Cytokine Activation. Inflammation 28, 53–58 (2004). https://doi.org/10.1023/B:IFLA.0000033020.28446.a6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:IFLA.0000033020.28446.a6

Search

Navigation