Skip to main content
SpringerLink
Log in

Antimicrobial Activity of Leukocytes

  • Chapter
Physiology of Inflammation

Part of the book series: Methods in Physiology Series ((METHPHYS))

Abstract

The reduction of oxygen by one electron creates superoxide (O2 −), a free radical with surprisingly little reactivity, except with itself. The reactive oxygen is reduced to water through the acceptance of three additional electrons. However, during this process the relatively inert O2 − gives rise to a series of highly reactive oxidants. The production of these oxidants is discussed in the following.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abo, A., Pick, E., Hall, A., Totty, N., Teahan, C. G., and Segal, A. W. (1991) Activation of the NADPH oxidase involves the small GTP-binding protein p2lracl. Nature 353: 668–670.

    Article  PubMed  CAS  Google Scholar 

  • Albrich, J. M., and Hurst, J. K. (1982) Oxidative inactivation of Escherichia coli by hypochlorous acid. Rates and differentiation of respiratory from other reactive sites. IEBS Lett. 144: 157–161.

    CAS  Google Scholar 

  • Andrews, P. C., and Krinsky, N. I. (1981) The reductive cleavage of myeloperoxidase in half, producing enzymically active hemi-myeloperoxidase. J. Biol. Chem. 256: 4211–4218.

    PubMed  CAS  Google Scholar 

  • Belaaouaj, A., McCarthy, R., Baumann, M., Gao, Z., Ley, S. N., Abraham, S. N., and Shapiro, S. D. (1998) Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat. Med. 4: 615–618.

    Article  PubMed  CAS  Google Scholar 

  • Bokoch, G. M., Quilliam, L. A., Bohl, B. P., Jesaitis, A. J., and Quinn, M. T. (1991) Inhibition of Rap lA binding to cytochrome b558 of NADPH oxidase by phosphorylation of Rap 1A. Science 254: 1794–1796.

    Article  PubMed  CAS  Google Scholar 

  • Bokoch, G. M., and Prossnitz, V. (1992) Isoprenoid metabolism is required for stimulation of the respiratory burst oxidase of HL-60 cells. j Clin. Invest. 89: 402–408.

    Article  PubMed  CAS  Google Scholar 

  • Borregaard, N., and Tauber, A. I. (1984) Subcellular localization of the human neutrophil NADPH-oxidase:b-cytochrome and associated flavoprotein. j Biol. Chem. 259: 47–52.

    PubMed  CAS  Google Scholar 

  • Borregaard, N., and Cowland, J. B. (1994) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89: 3503–3521.

    Google Scholar 

  • Byrd, T. F., and Horwitz, M. A. (1989) Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J. Clin. Invest. 83: 1457–1465.

    Article  PubMed  CAS  Google Scholar 

  • Carr, A. C., and Winterbourn, C. C. (1997) Oxidation of neutrophil glutathione and protein thiols by myeloperoxidase-derived hypochlorous acid. Biochem. J. 327: 275–281.

    PubMed  CAS  Google Scholar 

  • Cech, P., and Lehrer, R. I. (1984) Phagolysosomal pH of human neutrophils. Blood 63: 88–95.

    PubMed  CAS  Google Scholar 

  • Mendez, I., Garrett, M. C., Adams, A. G., and Leto, T. L. (1994) Role of p67-phox SH3 domains in assembly of the NADPH oxidase system. J. Biol. Chem. 269: 16326–16332.

    PubMed  Google Scholar 

  • Mendez, I., Adams, A. G., Sokolic, R. A., and Leto, T. L. (1996) Multiple SH3 domain interactions regulate NADPH oxidase assembly in whole cells. EMBO J. 15: 1211–1220.

    PubMed  Google Scholar 

  • Dinauer, M. C., Orkin, S. H., Brown, R., Jesaitis, A. J., and Parkos, C. A. (1987) The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complex. Nature 327: 717–720.

    Article  PubMed  CAS  Google Scholar 

  • Dusi, S., Della Bianca, V., Grzeskowiak, M., and Rossi, F. (1993) Relationship between phosphoAntimicrobial Activity of Leukocytes 201 rylation and translocation to the plasma membrane of p47phox and p67phox and activation of the NADPH oxidase in normal and Cat`-depleted human neutrophils. Biochem. J 290: 173–178.

    PubMed  CAS  Google Scholar 

  • Egesten, A., Breton-Gorius, J., Guichard, J., Gullberg, U., and Olsson, I. (1994) The heterogeneity of azurophil granules in neutrophil promyelocytes: immunogold localization of myeloperoxidase, cathepsin G, elastase, proteinase 3, and bactericidal/permeability increasing protein. Blood 70: 757–765.

    Google Scholar 

  • Eisenhauer, P. B., and Lehrer, R. I. (1992) Mouse neutrophils lack defensins. Infect. Immun. 60: 3446–3447.

    PubMed  CAS  Google Scholar 

  • Eiserich, J. P., Cross, C. E., Jones, A. D., Halliwell, B., and van der Vliet, A. (1996) Formation of nitrating and chlorinating species by reaction of nitrite with hypochlorous acid. A novel mechanism for nitric oxide-mediated protein modification. J. Biol. Chem. 271: 19199–19208.

    Article  PubMed  CAS  Google Scholar 

  • El Benna, J., Ruedi, J. M., and Babior, B. M. (1994) Cytosolic guanine nucleotide-binding protein Rac2 operates in vivo as a component of the neutrophil respiratory burst oxidase. Transfer of Rac2 and the cytosolic oxidase components p47r°ox and p67P“” to the submembranous actin cytoskeleton during oxidase activation. J. Biol. Chem. 269: 6729–6734.

    PubMed  Google Scholar 

  • Ellison, I.R.T. (1994) The effects of lactoferrin on gram-negative bacteria. Adv. Exp. Med. Biol 357: 71–90.

    Article  PubMed  CAS  Google Scholar 

  • Elsbach, P., Weiss, J., Wright, G., Forst, S., van den Bergh, C. J., and Verheij, H. M. (1990) Regulation and role of phospholipases in host—bacteria interaction. Prog. Clin. Biol. Res. 349: 1–9.

    PubMed  CAS  Google Scholar 

  • Elsbach, P., and Weiss, J. (1993) Bactericidal/permeability increasing protein and host defense against gram-negative bacteria and endotoxin. Curr. Opin. Immunol. 5: 103–107.

    Article  PubMed  CAS  Google Scholar 

  • Fenna, R., Zeng, J., and Davey, C. (1995) Structure of the green heme in myeloperoxidase. Arch. Biochem. Biophys. 316: 653–656.

    Article  PubMed  CAS  Google Scholar 

  • Fuchs, A., Bouin, A.-P., Rabilloud, T., and Vignais, P. V. (1997) The 40-kDa component of the phagocyte NADPH oxidase (p40phox) is phosphorylated during activation in differentiated HL60 cells. Eur. J. Biochem. 249: 531–539.

    Article  PubMed  CAS  Google Scholar 

  • Gabay, J. E., and Almeida, R. P. (1993) Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin. Curr. Opin. Immunol. 5: 97–102.

    Article  PubMed  CAS  Google Scholar 

  • Gallin, J. I., Fletcher, M. P., Seligmann, B. E., Hoffstein, S., Cehrs, K., and Mounessa, N. (1982) Human neutrophil-specific granule deficiency: A model to assess the role of neutrophilspecific granules in the evolution of the inflammatory response. Blood 59: 1317–1329.

    PubMed  CAS  Google Scholar 

  • Ganz, T., Metcalf, J. A., Gallin, J. I., Boxer, L. A., and Lehrer, R. I. (1988) Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak—Higashi syndrome and “specific” granule deficiency. J. Clin. Invest. 82: 552–556.

    Article  PubMed  CAS  Google Scholar 

  • Ganz, T., and Lehrer, R. I. (1995) Defensins. Pharmacol. Ther. 66: 191–205.

    Article  PubMed  CAS  Google Scholar 

  • Ganz, T., and Lehrer, R. I. (1997) Antimicrobial peptides of leukocytes. Curr. Opin. Hematol. 4: 53–58.

    Article  PubMed  CAS  Google Scholar 

  • Ganz, T., and Weiss, J. (1997) Antimicrobial peptides of phagocytes and epithelia. Semin. Hematol. 34: 343–354.

    PubMed  CAS  Google Scholar 

  • Gardner, P. R., Rainer, I., Epstein, L. B., and White, C. W. (1995) Superoxide radical and iron modulate aconitase activity in mammalian cells. J. Biol. Chem. 270: 13399–13405.

    Article  PubMed  CAS  Google Scholar 

  • Gebran, S. J., Newton, C., Yamamoto, Y., Widen, R., Klein, T. W., and Friedman, H. (1994) Macrophage permissiveness for Legionella pneumophila growth modulated by iron. Infect. Immun. 62: 564–568.

    PubMed  CAS  Google Scholar 

  • Gleich, G. J., and Adolphson, C. R. (1986) The eosinophilic leukocyte: structure and function. Adv. Immunol. 39: 177–253.

    Article  PubMed  CAS  Google Scholar 

  • Hackam, D. J., Rotstein, O. D., Zhang, W., Gruenheid, S., Gros, P., and Grinstein, S. (1998) Host resistance to intracellular infection: mutation of natural resistance-associated macrophage protein 1 (Nrampl) impairs phagosomal acidification. J. Exp. Med. 188: 351–364.

    Article  PubMed  CAS  Google Scholar 

  • Halliwell, B. (1987) Oxidants and human disease: some new concepts. PASEBJ. 1: 358–364.

    CAS  Google Scholar 

  • Hevel, J. M., White, K. A., and Marletta, M. A. (1991) Purification of the inducible murine macrophage nitric oxide synthase. J. Biol. Chem. 266: 22789–22791.

    PubMed  CAS  Google Scholar 

  • Heyworth, P. G., Shrimpton, C. F., and Segal, A. W. (1989) Localization of the 47 kDa phospho202 Physiology of Inflammation protein involved in the respiratory-burst NADPH oxidase of phagocytic cells. Biochem. J. 260: 243–248.

    PubMed  CAS  Google Scholar 

  • Heyworth, P. G., Knaus, U. G., Settleman, J., Curnutte, J. T., and Bokoch, G. M. (1993) Regulation of NADPH oxidase activity by Rac GTPase activating protein(s). Mol. Biol. Cell 4: 1217–1223.

    PubMed  CAS  Google Scholar 

  • Heyworth, P. G., Bohl, B. P., Bokoch, G. M., and Curnutte, J. T. (1994) Rac translocates independently of the neutrophil NADPH oxidase components p47r“°” and p67P“°” Evidence for its interaction with flavocytochrome b . J. Biol. Chem. 269: 30749–30752.

    PubMed  CAS  Google Scholar 

  • Higson, F. K., Kohen, R., and Chevion, M. (1988) Iron enhancement of ascorbate toxicity. Free Radie. Res. Commun. 5: 107–115.

    Article  CAS  Google Scholar 

  • Horwitz, M. A., and Maxfield, F. R. (1984) Legionella pneumophila inhibits acidification of its phagosome in human monocytes. j Cell Biol. 99: 1936–1943.

    CAS  Google Scholar 

  • Johnston, J. J., Boxer, L. A., and Berliner, N. (1992) Correlation of messenger RNA levels with protein defects in specific granule deficiency. Blood 80: 2088–2091.

    PubMed  CAS  Google Scholar 

  • Jones, S. A., Wood, J. D., Coffey, M. J., and Jones, O.T.G. (1994) The functional expression of p47-phox and p67-phox may contribute to the generation of superoxide by an NADPH oxidaselike system in human fibroblasts. FEBS Lett. 355: 178–182.

    Article  PubMed  CAS  Google Scholar 

  • Kettle, A. J., and Winterbourn, C. C. (1994) Superoxide-dependent hydroxylation by myeloperoxidase. J. Biol. Chem. 269: 17146–17151.

    PubMed  CAS  Google Scholar 

  • Koshkin, V., Lotan, O., and Pick, E. (1996) The cytosolic component p47r“°x is not a sine qua non participant in the activation of NADPH oxidase but is required for optimal superoxide production. J. Biol. Chem. 271: 30326–30329.

    Article  PubMed  CAS  Google Scholar 

  • Kramer, I J.M., Verhoeven, A. J., van der Bend, R. L., Weening, R. S., and Roos, D. (1988) Purified protein kinase C phosphorylates a 47 kDa protein in control neutrophil cytoplasts but not in neutrophil cytoplasts from patients with the autosomal form of chronic granulomatous disease. J. Biol. Chem. 263: 2352–2357.

    PubMed  CAS  Google Scholar 

  • Lee, S. J., and Stull, J. T. (1998) Calmodulin-dependent regulation of inducible and neuronal nitric-oxide synthase. J. Biol. Chem. 273: 27430–26437.

    Article  PubMed  CAS  Google Scholar 

  • Leffell, M. S., and Spitznagel, J. K. (1974) Intracellular and extracellular degranulation of human polymorphonuclear azurophl and specific granules induced by immune complexes. Infect. Immun. 10: 1241–1249.

    PubMed  CAS  Google Scholar 

  • Leffell, M. S., and Spitznagel, J. K. (1975) Fate of human lactoferrin and myeloperoxidase inphagocytizing human neutrophils: effects of immunoglobulin G subclasses and immune complexes coated on latex beads. Infect. Immun. 12: 813–820.

    PubMed  CAS  Google Scholar 

  • Lehrer, R. I., Szklarek, D., Barton, A., Ganz, T., Hamann, K. J., and Gleich, G. J. (1989) Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein. J. Immunol. 142: 4428–4434.

    PubMed  CAS  Google Scholar 

  • Levy, O. (1996) Antibiotic proteins of polymorphonuclear leukocytes. Eur. J. Haematol. 56: 263–277.

    Article  PubMed  CAS  Google Scholar 

  • Levy, R., Dana, R., Leto, T. L., and Malech, H. L. (1994) The requirement of p47 phosphorylation for activation of NADPH oxidase by opsonized zymosan in human neutrophils. Biochim. Biophys. Acta Mol. Cell Res. 1220: 253–260.

    Article  CAS  Google Scholar 

  • McCall, T. B., Boughton-Smith, N. K., Palmer, R. M., Whittle, B. J., and Moncada, S. (1989) Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem. J. 261: 293–296.

    PubMed  CAS  Google Scholar 

  • Murray, H. W., Szuro-Sudol, A., Wellner, D., Oca, M. J., Granger, A. M., Libby, D. M., Rothermel, C. D., and Rubin, B. Y. (1989) Role of tryptophan degradation in respiratory burst-independent antimicrobial activity of gamma interferon-stimulated human macrophages. Infect. Immun. 57: 845–849.

    PubMed  CAS  Google Scholar 

  • Nakamoto, R. K. (1996) Mechanisms of active transport in the Fo.F, ATP synthase. J Membr. Biol. 151: 101–111.

    Article  PubMed  CAS  Google Scholar 

  • Parkos, C. A., Allen, R. A., Cochrane, C. G., and Jesaitis, A. J. (1987) Purified cytochrome b from human granulocyte plasma membrane is comprised of two polypeptides with relative molecular weights of 91,000 and 22,000. J. Clin. Invest. 80: 732–742.

    Article  PubMed  CAS  Google Scholar 

  • Rathman, M., Sjaastad, M. D., and Falkow, S. (1996) Acidification of phagosomes containing Salmonella typhimurium in murine macrophages. Infect. Immun. 64: 2765–2773.

    PubMed  CAS  Google Scholar 

  • Rice, W. G., Ganz, T., Kinkade J. M. Jr., Selsted, M. E., Lehrer, R. I., and Parmley, R. T. (1987) Defensin-rich dense granules of human neutrophils. Blood 70: 757–765.

    PubMed  CAS  Google Scholar 

  • Rodriguez-Crespo, I., Gerber, N. C., and Ortiz de Montellano, P. R. (1996) Endothelial nitric-oxide synthase. Expression in Escherichia coli, spectroscopic characterization, and role of tetrahydrobiopterin in dimer formation. J. Biol. Chem. 271: 11462–11467.

    Article  PubMed  CAS  Google Scholar 

  • Rosen, H., Orman, J., Rakita, R. M., Michel, B. R., and VanDevanter, D. R. (1990) Loss of DNA-membrane interactions and cessation of DNA synthesis in myeloperoxidase-treated Escherichia coli. Proc. Natl. Acad. Sci. 87: 10048–10052.

    Article  CAS  Google Scholar 

  • Rotrosen, D., and Leto, T. L. (1990) Phosphorylation of neutrophil 47-kDa cytosolic oxidase factor. Translocation to membrane is associated with distinct phosphorylation events. J. Biol. Chem. 265: 19910–19915.

    PubMed  CAS  Google Scholar 

  • Salvemini, D., Nucci, G., Gryglewski, R. J., and Vane, J. R. (1989) Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc. Natl. Acad. Sci. 86: 6328–6332.

    Article  PubMed  CAS  Google Scholar 

  • Shi, J., and Ganz, T. (1998) The role of protegrins and other elastase-activated polypeptides in the bactericidal properties of porcine inflammatory fluids. Infect. Immun. 66: 3611–3617.

    PubMed  CAS  Google Scholar 

  • Sohnle, P. G., Hahn, B. L., and Santhanagopalan, V. (1996) Inhibition of Candida albicans growth by calprotectin in the absence of direct contact with the organisms. J. Infect. Dis. 174: 1369–1372.

    Article  PubMed  CAS  Google Scholar 

  • Someya, A., I. Nagaoka, and T. Yamashita (1993). Purification of the 260 kDa cytosolic complex involved in the superoxide production of guinea pig neutrophils. FEBS Lett. 330: 215–218.

    Article  PubMed  CAS  Google Scholar 

  • Steinbeck, M. J., Khan, A. U., Karnovsky, M. J., and Hegg, G. G. (1992) Intracellular singlet oxygen generation by phagocytosing neutrophils in response to particles coated with a chemical trap. J. Biol. Chem. 267: 13425–13433.

    PubMed  CAS  Google Scholar 

  • Sur, S., Glitz, D. G., Kita, H., Kujawa, S. M., Peterson, E. A., Weiler, D. A., Kephart, G. M., Wagner, J. M., George, T.J., Gleich, G. J., and Lederman, K. M. (1998) Localization of eosinophildrived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes. J. Leukoc. Biol. 63: 715–722.

    PubMed  CAS  Google Scholar 

  • Taylor, M. W., and Feng, G.-S. (1991) Relationship between interferon-gamma, indoleamine 2,3dioxygenase, and tryptophan catabolism. FASEB J 5: 2516–2522.

    PubMed  CAS  Google Scholar 

  • Thomas, E. L., Jefferson, M. M., and Grisham, M. (1982) Myeloperoxidase-catalyzed incorporation of amino acids into proteins: Role of hypochlorous acid and chloramines. Biochemistry 21: 6299–6308.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, E. L., Grisham, M. B., and Jefferson, M. M. (1983) Myeloperoxidase-dependent effect of amines on functions of isolated neutrophils. J. Clin. Invest. 72: 441–454.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, E. L., Bozeman, P. M., Jefferson, M. M., and King, C. C. (1995) Oxidation of bromide by the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase. Formation of bromamines. J. Biol. Chem. 270: 2906–2913.

    Article  PubMed  CAS  Google Scholar 

  • Uppu, R. M., Squadrito, G. L., and Pryor, W. A. (1996) Acceleration of peroxynitrite oxidations by carbon dioxide. Arch. Biochem. Biophys. 327: 335–343.

    Article  PubMed  CAS  Google Scholar 

  • Weinrauch, Y., Elsbach, P., Madsen, L. M., Foreman, A., and Weiss, J. (1996) The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase A2. J. Clin. Invest. 97: 250–257.

    Article  PubMed  CAS  Google Scholar 

  • Zanetti, M. R., Gennaro, R., and Romeo, D. (1995) Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett. 374: 1–5.

    Article  PubMed  CAS  Google Scholar 

  • Zeya, H. I., and Spitznagel, J. K. (1963) Antibacterial and enzymic basic proteins from leukocyte lysosomes: separation and identification. Science 142: 1085–1087.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Bernard M. Babior
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carolyn R. Hoyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert I. Lehrer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomas Ganz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia, USA

    Klaus Ley M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2001 American Physiological Society

About this chapter

Cite this chapter

Babior, B.M., Hoyal, C.R., Lehrer, R.I., Ganz, T. (2001). Antimicrobial Activity of Leukocytes. In: Ley, K. (eds) Physiology of Inflammation. Methods in Physiology Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7512-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7512-5_10

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-7512-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation