1887

Abstract

During phagocytosis, neutrophils undergo a burst of respiration in which oxygen is reduced to superoxide (O ), which dismutates to form HO. Myeloperoxidase (MPO) is discharged from the cytoplasmic granules into the phagosome following particle ingestion. It is thought to utilize HO to oxidize halides, which then react with and kill ingested microbes. Recent studies have provided new information as to the concentration of O and proteins, and the pH, within the vacuole. This study was conducted to examine the antimicrobial effect of O , HO and hypochlorous acid under these conditions and it was found that the previously described bactericidal effect of these agents was reversed in the presence of granule proteins or MPO. To establish which cellular proteins were iodinated by MPO, cellular proteins and bacterial proteins, iodinated in neutrophils phagocytosing bacteria in the presence of I, were separated by 2D gel electrophoresis. Iodinated spots were detected by autoradiography and the oxidized proteins were identified by MS. The targets of these iodination reactions were largely those of the host cell rather than those of the engulfed microbe.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.05181-0
2003-08-01
2019-10-22
Loading full text...

Full text loading...

/deliver/fulltext/jmm/52/8/JM520807.html?itemId=/content/journal/jmm/10.1099/jmm.0.05181-0&mimeType=html&fmt=ahah

References

  1. Aratani, Y., Koyama, H., Nyui, S. I., Suzuki, K., Kura, F. & Maeda, N. ( 1999;). Severe impairment in early host defense against Candida albicans in mice deficient in myeloperoxidase. Infect Immun 67, 1828–1836.
    [Google Scholar]
  2. Babior, B. M., Kipnes, R. S. & Curnutte, J. T. ( 1973;). Biological defence mechanisms: the production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 52, 741–744.[CrossRef]
    [Google Scholar]
  3. Babior, B. M., Curnutte, J. T. & Kipnes, R. S. ( 1974;). Biological defense mechanisms.Evidence for the participation of superoxide in bacterial killing by xanthine oxidase. J Lab Clin Med 85, 235–244.
    [Google Scholar]
  4. Belding, M. E. & Klebanoff, S. J. ( 1970;). Peroxidase-mediated virucidal systems. Science 167, 195–196.[CrossRef]
    [Google Scholar]
  5. Brennan, M. L., Anderson, M. M., Shih, D. M. & 10 other authors ( 2001;). Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest 107, 419–430.[CrossRef]
    [Google Scholar]
  6. Cech, P. & Lehrer, R. I. ( 1984;). Phagolysosomal pH of human neutrophils. Blood 63, 88–95.
    [Google Scholar]
  7. Chang, Y., Segal, B., Holland, S., Miller, G. & Kwon-Chung, K. ( 1998;). Virulence of catalase-deficient Aspergillus nidulans in p47phox −/−mice.Implications for fungal pathogenicity and host defence in chronic granulomatous disease. J Clin Invest 101, 1843–1850.[CrossRef]
    [Google Scholar]
  8. Chapman, A. L., Hampton, M. B., Senthilmohan, R., Winterbourn, C. C. & Kettle, A. J. ( 2002;). Chlorination of bacterial and neutrophil proteins during phagocytosis and killing of Staphylococcus aureus. J Biol Chem 277, 9757–9762.[CrossRef]
    [Google Scholar]
  9. Dychdala, G. R. ( 2001;). Chlorine and chlorine compounds. In Disinfection, Sterilization and Preservation, 5th edn, pp. 135–158. Edited by S. S. Block. Philadelphia: Lippincott Williams & Wilkins.
  10. Forehand, J. R., Nauseef, W. M., Curnutte, J. T. & Johnston, R. B. ( 1995;). Inherited disorders of phagocyte killing. In The Metabolic and Molecular Bases of Inherited Disease, 7th edn, pp. 3995–4026. Edited by C. R. Scriver, A. L. Beaudet, W. S. Sly & D. Valle. New York: McGraw-Hill.
  11. Henson, P. M. ( 1971;). Interaction of cells with immune complexes: adherence, release of constituents and tissue injury. J Exp Med 134, 114–118.
    [Google Scholar]
  12. Hurst, J. K. & Barrette, W. C., Jr ( 1989;). Leukocytic oxygen activation and microbicidal oxidative toxins. Crit Rev Biochem Mol Biol 24, 271–328.[CrossRef]
    [Google Scholar]
  13. Jiang, Q., Griffin, D., Barofsky, D. & Hurst, J. ( 1997;). Intraphagosomal chlorination dynamics and yields determined using unique fluorescent bacterial mimics. Chem Res Toxicol 10, 1080–1089.[CrossRef]
    [Google Scholar]
  14. Kettle, A. J. & Winterbourn, C. C. ( 1988;). Superoxide modulates the activity of myeloperoxidase and optimizes the production of hypochlorous acid. Biochem J 252, 529–536.
    [Google Scholar]
  15. Kettle, A. J. & Winterbourn, C. C. ( 2001;). A kinetic analysis of the catalase activity of myeloperoxidase. Biochemistry 40, 10204–10212.[CrossRef]
    [Google Scholar]
  16. Klebanoff, S. J. ( 1967a;). Iodination of bacteria: a bactericidal mechanism. J Exp Med 126, 1063–1078.[CrossRef]
    [Google Scholar]
  17. Klebanoff, S. J. ( 1967b;). A peroxidase-mediated antimicrobial system in leukocytes. J Clin Invest 126, 1063–1078.
    [Google Scholar]
  18. Klebanoff, S. J. ( 1968;). Myeloperoxidase-halide-hydrogen peroxide antibacterial system. J Bacteriol 95, 2131–2138.
    [Google Scholar]
  19. Klebanoff, S. J. ( 1970;). Myeloperoxidase: contribution to the microbicidal activity of intact leukocytes. Science 169, 1095–1097.[CrossRef]
    [Google Scholar]
  20. Klebanoff, S. J. ( 1975;). Antimicrobial mechanisms in neutrophilic polymorphonuclear leukocytes. Semin Hematol 12, 117–142.
    [Google Scholar]
  21. Klebanoff, S. J. & Clark, R. A. ( 1976;). Iodination by human polymorphonuclear leukocytes: a re-evaluation. J Lab Clin Med 89, 675–686.
    [Google Scholar]
  22. Lehrer, R. I. ( 1969;). Antifungal effects of peroxidase systems. J Bacteriol 99, 361–365.
    [Google Scholar]
  23. Mandell, G. L. & Hook, E. W. ( 1969;). Leukocyte bactericidal activity in chronic granulomatous disease: correlation of bacterial hydrogen peroxide production and susceptibility to intracellular killing. J Bacteriol 100, 531–532.
    [Google Scholar]
  24. Messina, C. G. M., Reeves, E. P., Roes, J. & Segal, A. W. ( 2002;). Catalase negative Staphylococcus aureus retain virulence in mouse model of chronic granulomatous disease. FEBS Lett 518, 107–110.[CrossRef]
    [Google Scholar]
  25. Nagl, M., Hess, M., Pfaller, K., Hengster, P. & Gottardi, W. ( 2000;). Bactericidal activity of micromolar N-chlorotaurine: evidence for its antimicrobial function in the human defence system. Antimicrob Agents Chemother 44, 2507–2513.[CrossRef]
    [Google Scholar]
  26. Olsen, R. & Little, C. ( 1982;). Purification and some of the properties of myeloperoxidase and eosinophil peroxidase from human blood. Biochem J 209, 781–787.
    [Google Scholar]
  27. Reeves, E. P., Lu, H., Hugues Lortat, J. & 7 other authors ( 2002;). Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416, 291–296.[CrossRef]
    [Google Scholar]
  28. Root, R. K., Metcalf, J., Oshino, N. & Chance, B. ( 1975;). H2O2 release from human granulocytes during phagocytosis.I. Documentation, quantitation and some regulating factors. J Clin Invest 55, 945–955.[CrossRef]
    [Google Scholar]
  29. Rosen, H. & Klebanoff, S. J. ( 1979;). Bactericidal activity of a superoxide anion-generating system.A model for the polymorphonuclear leukocyte. J Exp Med 149, 27–32.[CrossRef]
    [Google Scholar]
  30. Rosenfeld, J., Capdevielle, J., Guillemot, J. C. & Ferrara, P. ( 1992;). In-gel digestion of proteins for internal sequence analysis after one- or two-dimensional gel electrophoresis. Anal Biochem 203, 173–179.[CrossRef]
    [Google Scholar]
  31. Schiller, J., Benard, S., Reichl, S., Arnhold, J. & Arnold, K. ( 2000;). Cartilage degradation by stimulated human neutrophils: reactive oxygen species decrease markedly the activity of proteolytic enzymes. Chem Biol 7, 557–568.[CrossRef]
    [Google Scholar]
  32. Segal, A. W. & Jones, O. T. ( 1980;). Rapid incorporation of the human neutrophil plasma membrane cytochrome b into phagocytic vacuoles. Biochem Biophys Res Commun 92, 710–715.[CrossRef]
    [Google Scholar]
  33. Segal, A. W., Geisow, M., Garcia, R., Harper, A. & Miller, R. ( 1981;). The respiratory burst of phagocytic cells is associated with a rise in vacuolar pH. Nature 290, 406–409.[CrossRef]
    [Google Scholar]
  34. Segal, A. W., Garcia, R. C., Harper, A. M. & Banga, J. P. ( 1983;). Iodination by stimulated human neutrophils.Studies on its stoichiometry, subcellular localization and relevance to microbial killing. Biochem J 210, 215–225.
    [Google Scholar]
  35. Test, S. T., Lampert, M. B., Ossanna, P. J., Thoene, J. G. & Weiss, S. J. ( 1984;). Generation of nitrogen-chlorine oxidants by human phagocytes. J Clin Invest 74, 1341–1349.[CrossRef]
    [Google Scholar]
  36. Thomas, E. L. ( 1979;). Myeloperoxidase, hydrogen peroxide, chloride antimicrobial system: nitrogen-chlorine derivatives of bacterial components in bacterial action against Escherichia coli. Infect Immun 23, 522–531.
    [Google Scholar]
  37. Thrasher, A. J., Keep, N. H., Wientjes, F. B. & Segal, A. W. ( 1994;). Chronic granulomatous disease. Biochim Biophys Acta 1227, 1–24.[CrossRef]
    [Google Scholar]
  38. Vita, F., Borelli, V., Soranzo, M. R., Magnarin, M., Bertoncin, P. & Zabucchi, G. ( 1997;). Preparation of membrane fractions from human neutrophil granules: a simple method. Methods Cell Sci 19, 197–205.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.05181-0
Loading
/content/journal/jmm/10.1099/jmm.0.05181-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error