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Effects of bacteriophages on free radical production and phagocytic functions

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Abstract

Reactive oxygen species (ROS) play a major role in mediating antibacterial functions of phagocytic cells. However, excessive ROS production may cause oxidative stress and tissue damage. Uncompensated ROS release has been implicated in a variety of disorders. Novel means of controlling elevated ROS production are urgently needed. We showed that homologous but not the heterologous phages inhibited, in a dose dependent manner, the degree of chemiluminescence in phagocytes induced by Escherichia coli. Treatment of the cells with the phages alone resulted in a small increase in ROS production. Homologous phages also facilitated phagocytosis when preincubated with bacteria. On the other hand, both homologous and heterologous phages inhibited phagocytosis following preincubation with phagocytic cells. The treatment of infected and uninfected mice with phages did not significantly alter the rate of phagocytosis by blood granulocytes and monocytes. In conclusion, we showed that bacteriophages can decrease ROS production by phagocytes. Although in some in vitro experimental models the phages tended to diminish phagocytosis, this phenomenon may be of little significance in clinical situations, since the process of eliminating bacteria in phage-treated patients is predominantly accomplished by both phages and phagocytes.

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References

  1. Adams MH (1959) Bacteriophages. Interscience Publ, New York

    Google Scholar 

  2. Akaike T (2001) Role of free radicals in viral pathogenesis and mutation. Rev Med Virol 11:87–101

    Article  PubMed  CAS  Google Scholar 

  3. Asehnoune K, Strassheim D, Mitra S, Kim JY, Abraham E (2004) Involvement of reactive oxygen species in toll-like receptor 4-dependent activation of NF-κB. J Immunol 172:2522–2529

    PubMed  CAS  Google Scholar 

  4. Betten A, Dahlgren C, Mellqvist UH, Hermodsson S, Hellstrand K (2004) Oxygen-radical induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin. J Leukocyt Biol 75:1111–1115

    Article  CAS  Google Scholar 

  5. Bogozova G, Voroshilova N. Bondarenko VM (1991) The efficacy of Klebsiella pneumoniae bacteriophage in the therapy of experimental Klebsiella infection. Zh Mikrobiol Epidemiol Immunobiol 4:5–8

    Google Scholar 

  6. Boratyński J, Syper D, Weber-Dąbrowska B, Łusiak- Szelachowska M, Pozniak G, Górski A (2004) Preparation of endotoxin-free bacteriophages. Cell Mol Biol Lett 9:253–259

    PubMed  Google Scholar 

  7. Bruttin A, Brussow H (2005) Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy. Antimicrob Agents Chemother 49:2874–2878

    Article  PubMed  CAS  Google Scholar 

  8. Cerimele F, Battle T, Lynch R, Frank DA, Murad E, Cohen C, Macaron N, Sixbey J, Smith K, Watnick RS, Eliopoulos A, Shehata B, Arbiser JL (2005) Reactive oxygen signaling and MAPK activation distinguish Epstein–Barr Virus (EBV)—positive versus EBV-negative Burkitt’s lymphoma. Proc Natl Acad Sci USA 102:175–179

    Article  PubMed  CAS  Google Scholar 

  9. Dandona P, Kumar V, Aljada A, Ghanim H, Syed T, Hofmeyer D, Mohanty P Tripathy D, Garg R (2003) Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, NF-κB, in mononuclear cells of normal subjects: evidence for anti inflammatory action. J Clin Endocrinol Metab 88:4496–4501

    Article  PubMed  CAS  Google Scholar 

  10. De Meester I, Korom S, Van Damme J, Scharpe S (1999) CD26, let it cut or cut it down. Immunol Today 20:367–375

    Article  PubMed  Google Scholar 

  11. El-Benna J, Dang PM, Gougerot-Pocidalo MA, Elbim C (2005) Phagocyte NADPH oxidase: a multicomponent enzyme essential for host defenses. Arch Immunol Ther Exp 53:199–206

    CAS  Google Scholar 

  12. Friend DS, Rosenau W, Winfield JS, Moon DH (1969) Uptake and degradation of T2 bacteriophage by rat peritoneal macrophages. Lab Invest 20:275–282

    PubMed  CAS  Google Scholar 

  13. Fujimaki Y, Shimoyama T, Liu Q, Umeda T, Nakaji S, Sugawara K (2003) Low level laser irradiation attentuates production of reactive oxygen species by human neutrophils. J Clin Laser Med Surg 21:165–170

    Article  PubMed  Google Scholar 

  14. Gorski A, Dabrowska K, Switala-Jelen K, Nowaczyk M, Weber-Dabrowska B, Boratynski J, Wietrzyk J, Opolski A (2003) New insights into the possible role of bacteriophages in host defense and disease. Med Immunol 2:2

    Article  PubMed  Google Scholar 

  15. Górski A, Weber-Dąbrowska B (2005) The potential role of endogenous bacteriophages in controlling invading pathogens. Cell Mol Life Sci 62:511–519

    Article  PubMed  CAS  Google Scholar 

  16. Górski A, Kniotek M, Perkowska-Ptasińska A, Mróz A, Przerwa A, Gorczyca W, Dąbrowska K, Weber-Dąbrowska B, Nowaczyk M (2005) Bacteriophages and transplantation tolerance. Transplant Proc (in press)

  17. Gregory SH, Sagnimeni AJ, Wing EJ (1996) Bacteria in the bloodstream are trapped in the liver and killed by immigrating neutrophils. J Immunol 157:2514–2520

    PubMed  CAS  Google Scholar 

  18. Gregory SH, Cousens LP, van Rooijen N, Dopp EA, Carlos TM, Wing EJ (2002) Complementary adhesion molecules promote neutrophil–Kupffer cell interaction and the elimination of bacteria taken up by the liver. J Immunol 168:308–315

    PubMed  CAS  Google Scholar 

  19. Gul M, Kurutas E, Ciragil P, Cetinkaya A, Kilinc M, Aral M, Buyukbese MA (2005) Urinary tract infection aggravates oxidative stress in diabetic patients. Tohoku J Exp Med 206:1–6

    Article  PubMed  CAS  Google Scholar 

  20. Iida T, Umezawa K, Tanaka K, Koga Y, Nakazawa H, Satoh T (1997) Polymorphonuclear cells in chronic hemodialysis patients have intact phagocytotic and impaired bactericidal activities. Nephron 75:41–47

    Article  PubMed  CAS  Google Scholar 

  21. Kampen AH, Tollersrud T, Larsen S, Roth JA, Frank DE, Lund A (2004) Repeatability of flow cytometric and classical measurement of phagocytosis and respiratory burst in bovine polymorphonuclear leukocytes. Vet Immunol Immunopathol 97:105–114

    Article  PubMed  CAS  Google Scholar 

  22. Kańtoch M (1958) Studies on phagocytosis of bacterial viruses. Arch Immun Ther Exp 6:63–84

    Google Scholar 

  23. Malmberg KJ (2004) Effective immunotherapy against cancer: a question of overcoming immune suppression and immune escape? Cancer Immun Immunther 53:879–892

    CAS  Google Scholar 

  24. Merril CR, Biswas B, Carlton R, Jensen NC, Creed GJ, Zullo S, Adhya S (1996) Long-circulating bacteriophage as antibacterial agents. Proc Natl Acad Sci USA 93:3188–3192

    Article  PubMed  CAS  Google Scholar 

  25. Międzybrodzki R, Fortuna W, Weber-Dąbrowska B, Górski A (2005) Bacterial viruses against viruses pathogenic for man? Virus Res 110:1–8

    Article  PubMed  CAS  Google Scholar 

  26. Oberley LW (2005) Mechanism of the tumor suppressive effect of MnSOD overexpression. Biomed Pharmacother 59:143–148

    Article  PubMed  CAS  Google Scholar 

  27. Pawlak W, Kedziora J, Zolynski K, Kedziora-Kornatowska K, Blaszczyk J, Witkowski P (1998) Free radicals generation by granulocytes from men during bed rest. J Gravit Physiol 5:131–132

    Google Scholar 

  28. Pontes GN, Massironi SG, Arslanian C, Palmeira P, Carneiro-Sampaio MM, Nagao AT (2005) Human IgG but not IgM antibodies can protect mice from the challenge with live 06 E. coli. Scand J Immunol 62:355–60

    Article  CAS  Google Scholar 

  29. Riedemann NC, Guo RF, Ward PA (2003) Novel strategies for the treatment of sepsis. Nat Med 9:517–524

    Article  PubMed  CAS  Google Scholar 

  30. Sanlioglu S, Williams CM, Samarati L, Butler NS, Wang G, McGray Pb Jr, Ritchie TC, Hunninghake GW, Zandi E, Engelhardt JF (2001) LPS induces Rac1-dependent ROS formation and coordinates TNF-alpha secretion through IKK regulation of NF-κB. J Biol Chem 276:30188–30198

    Article  PubMed  CAS  Google Scholar 

  31. Sikora JP (2002) Immunotherapy in the management of sepsis. Arch Immunol Ther Exp 50:317–324

    CAS  Google Scholar 

  32. Valyi-Nagi T, Dermody TS (2005) Role of oxidative damage in the pathogenesis of viral infections of the nervous system. Histol Histopathol 20:957–967

    Google Scholar 

  33. Victor VM, Rocha M, De la Fuente M (2004) Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol 4:327–347

    Article  PubMed  CAS  Google Scholar 

  34. Weber-Dąbrowska B, Mulczyk M, Górski A (2000) Bacteriophage therapy for bacterial infections: an update of our institute’s experience. Arch Immun Ther Exp 48:547–551

    Google Scholar 

  35. Weber-Dąbrowska B, Zimecki M, Mulczyk M (2000) Effective phage therapy is associated with normalization of cytokine production by blood cell cultures. Arch Immunol Ther Exp 48:31–37

    Google Scholar 

  36. Weber-Dąbrowska B, Zimecki M, Mulczyk M Górski A (2002) Effect of phage therapy on the turnover and function of peripheral neutophils. FEMS Immunol Med Microbiol 34:135–138

    Article  PubMed  Google Scholar 

  37. Weber-Dąbrowska B, Mulczyk M, Górski A (2003) Bacteriophages as an efficient therapy for antibiotic-resistant septicemia in man. Transplant Proc 35:1385–1386

    Article  PubMed  Google Scholar 

  38. Yoshino S, Yamaki K, Taneda S, Yanagisawa R, Takano H (2005) Reactivation of antigen-induced arthritis in mice by oral administration of LPS. Scand J Immunol 62:117–122

    Article  PubMed  CAS  Google Scholar 

  39. Yu F, Mizushima S (1982) Roles of lipopolysaccharide and outer membrane protein OmpC of Escherichia coli K-12 in the receptor function for bacteriophage T4. J Bacteriol 151:718–722

    PubMed  CAS  Google Scholar 

  40. Zhou Y, Gregor VE, Sun Z, Ayida BK, Winters GC, Murphy D, Simonsen KB, Vourloumis D, Fish S, Froelich JM, Wall D, Hermann T (2005) Structure-guided discovery of novel aminoglycoside mimetics as antibacterial translation inhibitors. Antimicrob Agent Chemother 49:4942–4949

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from Ministry of Science PBZ-MIN-007/PO4/2003 and The Medical University of Warsaw intramural grant 1MG/W1. K. D. is a recipient of the L’Oreal-UNESCO for Woman in Science Award, Polish Edition 2004.

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Authors and Affiliations

  1. Transplantation Institute, Medical University of Warsaw, 02-006, Warsaw, Poland

    Anna Przerwa & Andrzej Górski

  2. L.Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114, Wroclaw, Poland

    Michał Zimecki, Kinga Świtała-Jeleń, Krystyna Dąbrowska, Beata Weber-Dąbrowska, Danuta Syper, Ryszard Międzybrodzki & Andrzej Górski

  3. Department of Medical Microbiology, Medical University of Warsaw, 02-005, Warsaw, Poland

    Ewa Krawczyk & Mirosław Łuczak

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  1. Anna Przerwa
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  2. Michał Zimecki
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  3. Kinga Świtała-Jeleń
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  4. Krystyna Dąbrowska
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Correspondence to Andrzej Górski.

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Przerwa, A., Zimecki, M., Świtała-Jeleń, K. et al. Effects of bacteriophages on free radical production and phagocytic functions. Med Microbiol Immunol 195, 143–150 (2006). https://doi.org/10.1007/s00430-006-0011-4

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  • DOI: https://doi.org/10.1007/s00430-006-0011-4

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