Chapter 18 : Antimicrobial Proteins

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Antimicrobial proteins are widely distributed in host defense cells and secretions. Antimicrobial proteins are also abundant in the secretions of epithelia exposed to environmental microbes (e.g., in the skin, nose and bronchi, the mouth, and the surface of the eyes). Classical characterization of antimicrobial proteins usually requires their extraction from the tissues or cells of origin, followed by activity-guided purification to homogeneity. Some antimicrobial proteins are enzymes that lyse the protein, lipid, carbohydrate, or perhaps nucleic acid components of microbes. Lysozyme is widely distributed in animal tissues. In humans, high concentrations of lysozyme are present in the cytoplasmic granules of neutrophils and Paneth cells, and in cellular and secretory compartments of monocytes and macrophages. Mice lacking neutrophil elastase are susceptible to infections with gram-negative bacteria, and mice doubly deficient in neutrophil elastase and cathepsin G are susceptible to fungal infection with and resistant to the endothelial injury seen in endotoxic shock, suggesting an important role for serprocidins in both host defense and its pathological consequences. Both epithelia and phagocytes secrete protease inhibitors, of which the secretory leukoprotease inhibitor (SLPI) is the most abundant. Granulysin and its fragments display a broad spectrum of activity against many bacteria including , and the protein has also been shown to contribute to CD8 T-cell-mediated killing of the yeast .

Citation: Ganz T, Lehrer R. 2004. Antimicrobial Proteins, p 345-356. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch18

Key Concept Ranking

Outer Membrane Proteins
Bacterial Proteins
Bacterial Cell Wall
Toll-Like Receptor 2
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1. Ashcroft, G. S.,, K. Lei,, W. Jin,, G. Longenecker,, A. B. Kulkarni,, T. Greenwell-Wild,, H. Hale- Donze,, G. McGrady,, X.Y. Song,, and S. M. Wahl. 2000. Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat. Med. 6:11471153.
2. Bangalore, N.,, J. Travis,, V. C. Onunka,, J. Pohl,, and W. M. Shafer. 1990. Identification of the primary antimicrobial domains in human neutrophil cathepsin G. J. Biol. Chem. 265:1358413588.
3. Beamer, L. J.,, S. F. Carroll,, and D. Eisenberg. 1999.The three-dimensional structure of human bactericidal/ permeability-increasing protein: implications for understanding protein-lipopolysaccharide interactions. Biochem. Pharmacol. 57:225229.
4. Belaaouaj, A. 2002. Neutrophil elastase-mediated killing of bacteria: lessons from targeted mutagenesis. Microb. Infect. 4:12591264.
5. Belaaouaj, A.,, R. McCarthy,, M. Baumann,, Z. Gao,, T. J. Ley,, S. N. Abraham,, and S. D. Shapiro. 1998. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat. Med. 4:615618.
6. Brandtzaeg, P.,, T. O. Gabrielsen,, I. Dale,, F. Muller,, M. Steinbakk,, and M. K. Fagerhol. 1995. The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at epithelial surfaces. Adv. Exp. Med. Biol. 371A:201206.
7. Braun, V.,, and H. Killmann. 1999. Bacterial solutions to the iron-supply problem. Trends Biochem. Sci. 24:104109.
8. Brock, J. H. 2002. The physiology of lactoferrin. Biochem. Cell Biol. 80:16.
9. Cole, A. M.,, J. Shi,, A. Ceccarelli,, Y. H. Kim,, A. Park,, and T. Ganz. 2001. Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds. Blood 97:297304.
10. Domachowske, J. B.,, K. D. Dyer,, C. A. Bonville,, and H. F. Rosenberg. 1998. Recombinant human eosinophil-derived neurotoxin/RNase 2 functions as an effective antiviral agent against respiratory syncytial virus. J. Infect. Dis. 177:14581464.
11. Elsbach, P.,, and J. Weiss. 1998. Role of the bactericidal/ permeability-increasing protein in host defence. Curr. Opin. Immunol. 10:4549.
12. Fleming, A. 1922. On a remarkable bacteriolytic element found in tissues and secretions. Proc. R. Soc. London B Biol. Sci. 93:306317.
13. Gabay, J. E.,, and R. P. Almeida. 1993. Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin. Curr. Opin. Immunol. 5:97102.
14. Ganz, T.,, and J. Weiss. 1997. Antimicrobial peptides of phagocytes and epithelia. Semin. Hematol. 34:343354.
15. Ganz, T.,, J. A. Metcalf,, J. I. Gallin,, L. A. Boxer,, and R. I. Lehrer. 1988. Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and “specific” granule deficiency. J. Clin. Invest. 82:552556.
16. Ganz, T.,, V. Gabayan,, H. I. Liao,, L. Liu,, A. Oren,, T. Graf,, and A. M. Cole. 2003. Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan. Blood 101:2388.
17. Ginsburg, I. 1988.The biochemistry of bacteriolysis: paradoxes, facts and myths. Microbiol. Sci. 5:137142.
18. Gleich, G. J.,, and C. R. Adolphson. 1986. The eosinophilic leukocyte: structure and function. Adv. Immunol. 39:177253.
19. Gleich, G. J.,, D. A. Loegering,, M. P. Bell,, J. L. Checkel,, S. J. Ackerman,, and D. J. McKean. 1986. Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease. Proc. Natl. Acad. Sci. USA 83:31463150.
20. Gronroos, J. O.,, V. J. Laine,, and T. J. Nevalainen. 2002. Bactericidal group IIA phospholipase A2 in serum of patients with bacterial infections. J. Infect. Dis. 185:17671772.
21. Harder, J.,, and J. M. Schroder. 2002. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J. Biol. Chem. 277:4677946784.
22. Hiemstra, P. S. 2002. Novel roles of protease inhibitors in infection and inflammation. Biochem. Soc. Trans. 30:116120.
23. Hiemstra, P. S.,, M. T. van den Barselaar,, M. Roest,, P. H. Nibbering,, and R. van Furth. 1999. Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages. J. Leukoc. Biol. 66:423428.
24. Hirsch, J. G. 1958. Bactericidal action of histone. J. Exp. Med. 108:925944.
25. Hobson, D.,, and J. G. Hirsch. 1958.The antibacterial activity of hemoglobin. J. Exp. Med. 107:167183.
26. Hoffmann, J. A.,, F. C. Kafatos,, C.A. Janeway,, and R. A. Ezekowitz. 1999. Phylogenetic perspectives in innate immunity. Science 284:13131318.
27. Iwanaga, S.,, S. Kawabata,, and T. Muta. 1998. New types of clotting factors and defense molecules found in horseshoe crab hemolymph: their structures and functions. J. Biochem. (Tokyo) 123:115.
28. Kang, D.,, G. Liu,, A. Lundstrom,, E. Gelius,, and H. Steiner. 1998. A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc. Natl. Acad. Sci. USA 95:1007810082.
29. Lehrer, R. I.,, D. Szklarek,, A. Barton,, T. Ganz,, K. J. Hamann,, and G. J. Gleich. 1989. Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein. J. Immunol. 142:44284434.
30. Liu, C.,, E. Gelius,, G. Liu,, H. Steiner,, and R. Dziarski. 2000. Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. J. Biol. Chem. 275:2449024499.
31. Ma, L. L.,, J. C. Spurrell,, J. F. Wang,, G. G. Neely,, S. Epelman,, A. M. Krensky,, and C. H. Mody. 2002. CD8 T cell-mediated killing of Cryptococcus neoformans requires granulysin and is dependent on CD4 T cells and IL-15. J. Immunol. 169:57875795.
32. Manitz, M. P.,, B. Horst,, S. Seeliger,, A. Strey,, B. V. Skryabin,, M. Gunzer,, W. Frings,, F. Schonlau,, J. Roth,, C. Sorg,, and W. Nacken. 2003. Loss of S100A9 (MRP14) results in reduced interleukin- 8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. Mol. Cell. Biol. 23: 10341043.
33. Mellor, A. L.,, and D. H. Munn. 1999.Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol.Today 20:469473.
34. Murthy, A. R.,, R. I. Lehrer,, S. S. Harwig,, and K. T. Miyasaki. 1993. In vitro candidastatic properties of the human neutrophil calprotectin complex. J. Immunol. 151:62916301.
35. Panyutich, A.,, J. Shi,, P. L. Boutz,, C. Zhao,, and T. Ganz. 1997. Porcine polymorphonuclear leukocytes generate extracellular microbicidal activity by elastasemediated activation of secreted proprotegrins. Infect. Immun. 65:978985.
36. Qu, X. D.,, and R. I. Lehrer. 1998. Secretory phospholipase A2 is the principal bactericide for staphylococci and other gram-positive bacteria in human tears. Infect. Immun. 66:27912797.
37. Reeves, E. P.,, H. Lu,, H. L. Jacobs,, C. G. Messina,, S. Bolsover,, G. Gabella,, E. O. Potma,, A. Warley,, J. Roes,, and A.W. Segal. 2002. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416:291297.
38. Singh, P. K.,, M. R. Parsek,, E. P. Greenberg,, and M. J. Welsh. 2002. A component of innate immunity prevents bacterial biofilm development. Nature 417: 552555.
39. Sohnle, P. G.,, B. L. Hahn,, and V. Santhanagopalan. 1996. Inhibition of Candida albicans growth by calprotectin in the absence of direct contact with the organisms. J. Infect. Dis. 174:13691372.
40. Sorensen, O. E.,, P. Follin,, A. H. Johnsen,, J. Calafat,, G. S. Tjabringa,, P. S. Hiemstra,, and N. Borregaard. 2001. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97:39513959.
41. Stenger, S.,, D. A. Hanson,, R. Teitelbaum,, P. Dewan,, K. R. Niazi,, C. J. Froelich,, T. Ganz,, S. Thoma-Uszynski,, A. Melian,, C. Bogdan,, S. A. Porcelli,, B. R. Bloom,, A. M. Krensky,, and R. L. Modlin. 1998.An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282:121125.
42. Swaminathan, G. J.,, A. J. Weaver,, D. A. Loegering,, J. L. Checkel,, D. D. Leonidas,, G. J. Gleich,, and K. R. Acharya. 2001. Crystal structure of the eosinophil major basic protein at 1.8 A. An atypical lectin with a paradigm shift in specificity. J. Biol. Chem. 276:2619726203.
43. Tang, Y. Q.,, M. R. Yeaman,, and M. E. Selsted. 2002. Antimicrobial peptides from human platelets. Infect. Immun. 70:65246533.
44. Taylor, M.W.,, and G. S. Feng. 1991. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism [see comments]. FASEB J. 5:25162522.
45. Tkalcevic, J.,, M. Novelli,, M. Phylactides,, J. P. Iredale,, A.W. Segal,, and J. Roes. 2000. Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G. Immunity 12:201210.
46. Tydell, C. C.,, N. Yount,, D. Tran,, J. Yuan,, and M. E. Selsted. 2002. Isolation, characterization, and antimicrobial properties of bovine oligosaccharidebinding protein. A microbicidal granule protein of eosinophils and neutrophils. J. Biol. Chem. 277:1965819664.
47. Ward, P. P.,, S. Uribe-Luna,, and O. M. Conneely. 2002. Lactoferrin and host defense. Biochem. Cell Biol. 80:95102.
48. Ward, P. P.,, M. Mendoza-Meneses,, G. A. Cunningham,, and O. M. Conneely. 2003. Iron status in mice carrying a targeted disruption of lactoferrin. Mol. Cell. Biol. 23:178185.
49. Weinrauch, Y.,, D. Drujan,, S. D. Shapiro,, J. Weiss,, and A. Zychlinsky. 2002. Neutrophil elastase targets virulence factors of enterobacteria. Nature 417:9194.
50. Weiss, J.,, G. Wright,, A. C. Bekkers,, C. J. van den Bergh,, and H. M. Verheij. 1991. Conversion of pig pancreas phospholipase A2 by protein engineering into enzyme active against Escherichia coli treated with the bactericidal/permeability-increasing protein. J. Biol. Chem. 266:41624167.
51. Wiese, A.,, K. Brandenburg,, B. Lindner,, A. B. Schromm,, S. F. Carroll,, E. T. Rietschel,, and U. Seydel. 1997. Mechanisms of action of the bactericidal/ permeability-increasing protein BPI on endotoxin and phospholipid monolayers and aggregates. Biochemistry 36:1030110310.
52. Zhu, J.,, C. Nathan,, W. Jin,, D. Sim,, G. S. Ashcroft,, S. M. Wahl,, L. Lacomis,, H. Erdjument-Bromage,, P. Tempst,, C. D. Wright,, and A. Ding. 2002. Conversion of proepithelin to epithelins. Roles of SLPI and elastase in host defense and wound repair. Cell 111:867878.


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Location of major antimicrobial proteins in cells and tissues

Citation: Ganz T, Lehrer R. 2004. Antimicrobial Proteins, p 345-356. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch18
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Antimicrobial enzymes

Citation: Ganz T, Lehrer R. 2004. Antimicrobial Proteins, p 345-356. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch18
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Key interactions of nonenzymatic antimicrobial proteins

Citation: Ganz T, Lehrer R. 2004. Antimicrobial Proteins, p 345-356. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch18

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