Biotechnology Letters

, Volume 27, Issue 18, pp 1337–1347 | Cite as

Human Antimicrobial Peptides: Defensins, Cathelicidins and Histatins

Review

Abstract

Antimicrobial peptides, which have been isolated from many bacteria, fungi, plants, invertebrates and vertebrates, are an important component of the natural defenses of most living organisms. The isolated peptides are very heterogeneous in length, sequence and structure, but most of them are small, cationic and amphipathic. These peptides exhibit broad-spectrum activity against Gram-positive and Gram-negative bacteria, yeasts, fungi and enveloped viruses. A wide variety of human proteins and peptides also have antimicrobial activity and play important roles in innate immunity. In this review we discuss three important groups of human antimicrobial peptides. The defensins are cationic non-glycosylated peptides containing six cysteine residues that form three intramolecular disulfide bridges, resulting in a triple-stranded β-sheet structure. In humans, two classes of defensins can be found: α-defensins and β-defensins. The defensin-related HE2 isoforms will also be discussed. The second group is the family of histatins, which are small, cationic, histidine-rich peptides present in human saliva. Histatins adopt a random coil conformation in aqueous solvents and form α-helices in non-aqueous solvents. The third group comprises only one antimicrobial peptide, the cathelicidin LL−37. This peptide is derived proteolytically from the C-terminal end of the human CAP18 protein. Just like the histatins, it adopts a largely random coil conformation in a hydrophilic environment, and forms an α-helical structure in a hydrophobic environment.

Key words:

antimicrobial peptides cathelicidin defensins histatins innate immunity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agerberth, B, Charo, J, Werr, J, Olsson, B, Idali, F, Lindbom, L, Kiessling, R, Jornvall, H, Wigzell, H, Gudmundsson, GH 2000The human antimicrobial and chemotactic peptides LL−37 and alpha-defensins are expressed by specific lymphocyte and monocyte populationsBlood9630863093PubMedGoogle Scholar
  2. Ahmad, M, Piludu, M, Oppenheim, FG, Helmerhorst, EJ, Hand, AR 2004Immunocytochemical localization of histatins in human salivary glandsJ. Histochem. Cytochem.52361370PubMedGoogle Scholar
  3. Axen, A, Carlsson, A, Engstrom, A, Bennich, H 1997Gloverin, an antibacterial protein from the immune hemolymph of Hyalophora pupaeEur. J. Biochem.247614619CrossRefPubMedGoogle Scholar
  4. Baev, D, Li, XS, Dong, J, Keng, P, Edgerton, M 2002Human salivary histatin 5 causes disordered volume regulation and cell cycle arrest in Candida albicansInfect. Immun.7047774784CrossRefPubMedGoogle Scholar
  5. Baev, D, Rivetta, A, Li, XS, Vylkova, S, Bashi, E, Slayman, CL, Edgerton, M 2003Killing of Candida albicans by human salivary histatin 5 is modulated, but not determined, by the potassium channel TOK1Infect. Immun.7132513260CrossRefPubMedGoogle Scholar
  6. Baev, D, Rivetta, A, Vylkova, S, Sun, JN, Zeng, GF, Slayman, CL, Edgerton, M 2004The TRK1 potassium transporter is the critical effector for killing of Candida albicans by the cationic protein, Histatin 5J. Biol. Chem.2795506055072CrossRefPubMedGoogle Scholar
  7. Bals, R 2000Epithelial antimicrobial peptides in host defense against infectionResp. Res.1141150CrossRefGoogle Scholar
  8. Bals, R, Wang, X, Zasloff, M, Wilson, JM 1998The peptide antibiotic LL−37/hCAP−18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surfaceProc. Natl. Acad. Sci. USA9595419546CrossRefPubMedGoogle Scholar
  9. Bals, R, Weiner, DJ, Moscioni, AD, Meegalla, RL, Wilson, JM 1999Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptideInfect. Immun.6760846089PubMedGoogle Scholar
  10. Bateman, A, Singh, A, Congote, LF, Solomon, S 1991The effect of HP−1 and related neutrophil granule peptides on DNA synthesis in HL60 cellsRegul. Pept.35135143CrossRefPubMedGoogle Scholar
  11. Bensch, KW, Raida, M, Magert, HJ, Schulz-Knappe, P, Forssmann, WG 1995hBD-1: a novel beta-defensin from human plasmaFEBS Lett.368331335CrossRefPubMedGoogle Scholar
  12. Boman, HG, Agerberth, B, Boman, A 1993Mechanisms of action on Escherichia coli of cecropin P1 and PR−39, two antibacterial peptides from pig intestineInfect. Immun.6129782984PubMedGoogle Scholar
  13. Brahmachary, M, Krishnan, SP, Koh, JL, Khan, AM, Seah, SH, Tan, TW, Brusic, V, Bajic, VB 2004ANTIMIC: a database of antimicrobial sequencesNucleic Acids Res.32D586D589CrossRefPubMedGoogle Scholar
  14. Castagnola, M, Inzitari, R, Rossetti, DV, Olmi, C, Cabras, T, Piras, V, Nicolussi, P, Sanna, MT, Pellegrini, M, Giardina, B, Messana, I 2004A cascade of 24 histatins (histatin 3 fragments) in human saliva. Suggestions for a pre-secretory sequential cleavage pathwayJ. Biol. Chem.2794143641443CrossRefPubMedGoogle Scholar
  15. Chaly, YV, Paleolog, EM, Kolesnikova, TS, Tikhonov, II, Petratchenko, EV, Voitenok, NN 2000Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cellsEur. Cytokine Netw.11257266PubMedGoogle Scholar
  16. Charp, PA, Rice, WG, Raynor, RL, Reimund, E, Kinkade, JM, Ganz, T, Selsted, ME, Lehrer, RI, Kuo, JF 1988Inhibition of protein kinase C by defensins, antibiotic peptides from human neutrophilsBiochem. Pharmacol.37951956CrossRefPubMedGoogle Scholar
  17. Chitnis, SN, Kameswari, DB, Prasad, KS 1993Induction of autolysis in starved Escherichia coli cells by seminalplasmin, an antimicrobial protein from bovine seminal plasmaFEMS Microbiol. Lett.112147150CrossRefPubMedGoogle Scholar
  18. Cowland, JB, Johnsen, AH, Borregaard, N 1995hCAP−18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granulesFEBS Lett.368173176CrossRefPubMedGoogle Scholar
  19. Fernandez Caleya, R, Gonzalez-Pascual, B, Garcia-Olmedo, F, Carbonero, P 1972Susceptibility of phytopathogenic bacteria to wheat purothionins in vitroAppl. Microbiol.239981000PubMedGoogle Scholar
  20. Smet, K, Reekmans, R, Contreras, R 2004Role of oxidative phosphorylation in histatin 5-induced cell death in Saccharomyces cerevisiaeBiotechnol. Lett.2617811785CrossRefPubMedGoogle Scholar
  21. Edgerton, M, Koshlukova, SE, Lo, TE, Chrzan, BG, Straubinger, RM, Raj, PA 1998Candidacidal activity of salivary histatins. Identification of a histatin 5-binding protein on Candida albicansJ. Biol. Chem.2732043820447CrossRefPubMedGoogle Scholar
  22. Engstrom, P, Carlsson, A, Engstrom, A, Tao, ZJ, Bennich, H 1984The antibacterial effect of attacins from the silk moth Hyalophora cecropia is directed against the outer membrane of Escherichia coliEmbo J.333473351PubMedGoogle Scholar
  23. Frohm, M, Agerberth, B, Ahangari, G, Stahle-Backdahl, M, Liden, S, Wigzell, H, Gudmundsson, GH 1997The expression of the gene coding for the antibacterial peptide LL−37 is induced in human keratinocytes during inflammatory disordersJ. Biol. Chem.2721525815263CrossRefPubMedGoogle Scholar
  24. Ganz, T, Selsted, ME, Lehrer, RI 1990DefensinsEur. J. Haematol.4418PubMedGoogle Scholar
  25. Ganz, T 2005Defensins and other antimicrobial peptides: a historical perspective and an updateComb. Chem. High Throughput Screen.8209217CrossRefPubMedGoogle Scholar
  26. Garcia, JR, Krause, A, Schulz, S, Rodriguez-Jimenez, FJ, Kluver, E, Adermann, K, Forssmann, U, Frimpong-Boateng, A, Bals, R, Forssmann, WG 2001Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activityFASEB J.1518191821PubMedGoogle Scholar
  27. Groisman, EA 1996Bacterial responses to host-defense peptidesTrends Microbiol4127128. discussion 128–129CrossRefPubMedGoogle Scholar
  28. Gudmundsson, GH, Agerberth, B, Odeberg, J, Bergman, T, Olsson, B, Salcedo, R 1996The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL−37 in␣granulocytesEur. J. Biochem.238325332CrossRefPubMedGoogle Scholar
  29. Guex, N, Peitsch, MC 1997SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modelingElectrophoresis1827142723CrossRefPubMedGoogle Scholar
  30. Gusman, H, Travis, J, Helmerhorst, EJ, Potempa, J, Troxler, RF, Oppenheim, FG 2001aSalivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal diseaseInfect. Immun.6914021408CrossRefGoogle Scholar
  31. Gusman, H, Lendenmann, U, Grogan, J, Troxler, RF, Oppenheim, FG 2001bIs salivary histatin 5 a metallopeptide?Biochim. Biophys. Acta15458695Google Scholar
  32. Gyurko, C, Lendenmann, U, Troxler, RF, Oppenheim, FG 2000Candida albicans mutants deficient in respiration are resistant to the small cationic salivary antimicrobial peptide histatin 5Antimicrob. Agents Chemother44348354CrossRefPubMedGoogle Scholar
  33. Hamil, KG, Sivashanmugam, P, Richardson, RT, Grossman, G, Ruben, SM, Mohler, JL, Petrusz, P, O’Rand, MG, French, FS, Hall, SH 2000HE2beta and HE2gamma, new members of an epididymis-specific family of androgen-regulated proteins in the humanEndocrinology14112451253CrossRefPubMedGoogle Scholar
  34. Hancock, RE, Diamond, G 2000The role of cationic antimicrobial peptides in innate host defencesTrends Microbiol.8402410CrossRefPubMedGoogle Scholar
  35. Harder, J, Bartels, J, Christophers, E, Schroder, JM 1997A peptide antibiotic from human skinNature387861CrossRefPubMedGoogle Scholar
  36. Harder, J, Bartels, J, Christophers, E, Schroder, JM 2001Isolation and characterization of human beta-defensin−3, a novel human inducible peptide antibioticJ. Biol. Chem.27657075713CrossRefPubMedGoogle Scholar
  37. Helmerhorst, EJ, Reijnders, IM, van’t Hof, W, Simoons-Smit, I, Veerman, EC, Amerongen, AV 1999aAmphotericin B- and fluconazole-resistant Candida spp., Aspergillus fumigatus, and other newly emerging pathogenic fungi are susceptible to basic antifungal peptidesAntimicrob. Agents Chemother43702704Google Scholar
  38. Helmerhorst, EJ, Breeuwer, P, van’t Hof, W, Walgreen-Weterings, E, Oomen, LC, Veerman, EC, Amerongen, AV, Abee, T 1999bThe cellular target of histatin 5 on Candida albicans is the energized mitochondrionJ. Biol. Chem.27472867291CrossRefGoogle Scholar
  39. Helmerhorst, EJ, Troxler, RF, Oppenheim, FG 2001The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen speciesProc. Natl. Acad. Sci. USA981463714642CrossRefPubMedGoogle Scholar
  40. Holbrook, IB, Molan, PC 1973A further study of the factors enhancing glycolysis in human salivaArch. Oral Biol.1812751282CrossRefPubMedGoogle Scholar
  41. Imatani, T, Kato, T, Minaguchi, K, Okuda, K 2000Histatin 5 inhibits inflammatory cytokine induction from human gingival fibroblasts by Porphyromonas gingivalisOral Microbiol. Immunol.15378382CrossRefPubMedGoogle Scholar
  42. Iontcheva, I, Oppenheim, FG, Troxler, RF 1997Human salivary mucin MG1 selectively forms heterotypic complexes with amylase, proline-rich proteins, statherin, and histatinsJ. Dent. Res.76734743PubMedGoogle Scholar
  43. Jensen, JL, Lamkin, MS, Oppenheim, FG 1992Adsorption of human salivary proteins to hydroxyapatite: a comparison between whole saliva and glandular salivary secretionsJ. Dent. Res.7115691576PubMedGoogle Scholar
  44. Joly, S, Maze, C, McCray, PB, Guthmiller, JM 2004Human beta-defensins 2 and 3 demonstrate strain-selective activity against oral microorganismsJ. Clin. Microbiol.4210241029CrossRefPubMedGoogle Scholar
  45. Jones, DE, Bevins, CL 1992Paneth cells of the human small intestine express an antimicrobial peptide geneJ. Biol. Chem.2672321623225PubMedGoogle Scholar
  46. Jones, DE, Bevins, CL 1993Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowelFEBS Lett.315187192CrossRefPubMedGoogle Scholar
  47. Kamysz, W, Okroj, M, Lukasiak, J 2003Novel properties of antimicrobial peptidesActa Biochim. Pol.50461469PubMedGoogle Scholar
  48. Kavanagh, K, Dowd, S 2004Histatins: antimicrobial peptides with therapeutic potentialJ. Pharm. Pharmacol.56285289CrossRefPubMedGoogle Scholar
  49. Koshlukova, SE, Araujo, MW, Baev, D, Edgerton, M 2000Released ATP is an extracellular cytotoxic mediator in salivary histatin 5-induced killing of Candida albicansInfect. Immun.6868486856CrossRefPubMedGoogle Scholar
  50. Koshlukova, SE, Lloyd, TL, Araujo, MW, Edgerton, M 1999Salivary histatin 5 induces non-lytic release of ATP from Candida albicans leading to cell deathJ. Biol. Chem.2741887218879CrossRefPubMedGoogle Scholar
  51. Leem, JY, Nishimura, C, Kurata, S, Shimada, I, Kobayashi, A, Natori, S 1996Purification and characterization of N-beta-alanyl−5-S-glutathionyl−3,4-dihydroxyphenylalanine, a novel antibacterial substance of Sarcophaga peregrina (flesh fly)J. Biol. Chem.2711357313577CrossRefPubMedGoogle Scholar
  52. Lehrer, RI 2004Primate defensinsNat. Rev. Microbiol.2727738CrossRefPubMedGoogle Scholar
  53. Li, XS, Reddy, MS, Baev, D, Edgerton, M 2003Candida albicans Ssa1/2p is the cell envelope binding protein for human salivary histatin 5J. Biol. Chem.2782855328561CrossRefPubMedGoogle Scholar
  54. Lichtenstein, A, Ganz, T, Selsted, ME, Lehrer, RI 1986In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytesBlood6814071410PubMedGoogle Scholar
  55. MacKay, BJ, Pollock, JJ, Iacono, VJ, Baum, BJ 1984aIsolation of milligram quantities of a group of histidine-rich polypeptides from human parotid salivaInfect. Immun.44688694Google Scholar
  56. MacKay, BJ, Denepitiya, L, Iacono, VJ, Krost, SB, Pollock, JJ 1984bGrowth-inhibitory and bactericidal effects of human parotid salivary histidine-rich polypeptides on Streptococcus mutansInfect. Immun.44695701Google Scholar
  57. Murakami, Y, Xu, T, Helmerhorst, EJ, Ori, G, Troxler, RF, Lally, ET, Oppenheim, FG 2002Inhibitory effect of synthetic histatin 5 on leukotoxin from Actinobacillus actinomycetemcomitansOral Microbiol. Immunol.17143149CrossRefPubMedGoogle Scholar
  58. Murphy, CJ, Foster, BA, Mannis, MJ, Selsted, ME, Reid, TW 1993Defensins are mitogenic for epithelial cells and fibroblastsJ. Cell. Physiol.155408413CrossRefPubMedGoogle Scholar
  59. Okumura, K, Itoh, A, Isogai, E, Hirose, K, Hosokawa, Y, Abiko, Y, Shibata, T, Hirata, M, Isogai, H 2004C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cellsCancer Lett.212185194CrossRefPubMedGoogle Scholar
  60. Oppenheim, FG, Xu, T, McMillian, FM, Levitz, SM, Diamond, RD, Offner, GD, Troxler, RF 1988Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicansJ. Biol. Chem.26374727477PubMedGoogle Scholar
  61. Oppenheim, JJ, Biragyn, A, Kwak, LW, Yang, D 2003Roles of antimicrobial peptides such as defensins in innate and adaptive immunityAnn. Rheum. Dis.62ii17ii21CrossRefPubMedGoogle Scholar
  62. Osterhoff, C, Kirchhoff, C, Krull, N, Ivell, R 1994Molecular cloning and characterization of a novel human sperm antigen (HE2) specifically expressed in the proximal epididymisBiol. Reprod.50516525PubMedGoogle Scholar
  63. Paquette, DW, Simpson, DM, Friden, P, Braman, V, Williams, RC 2002Safety and clinical effects of topical histatin gels in humans with experimental gingivitisJ. Clin. Periodontol.2910511058CrossRefPubMedGoogle Scholar
  64. Park, CB, Kim, HS, Kim, SC 1998Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functionsBiochem. Biophys. Res. Commun.244253257CrossRefPubMedGoogle Scholar
  65. Pollock, JJ, Denepitiya, L, MacKay, BJ, Iacono, VJ 1984Fungistatic and fungicidal activity of human parotid salivary histidine-rich polypeptides on Candida albicansInfect. Immun.44702707PubMedGoogle Scholar
  66. Raj, PA, Marcus, E, Sukumaran, DK 1998Structure of human salivary histatin 5 in aqueous and nonaqueous solutionsBiopolymers455167CrossRefPubMedGoogle Scholar
  67. Reddy, KV, Yedery, RD, Aranha, C 2004Antimicrobial peptides: premises and promisesInt. J. Antimicrob. Agents24536547CrossRefPubMedGoogle Scholar
  68. Rothstein, DM, Spacciapoli, P, Tran, LT, Xu, T, Roberts, FD, Dalla Serra, M, Buxton, DK, Oppenheim, FG, Friden, P 2001Anticandida activity is retained in P−113, a 12-amino-acid fragment of histatin 5Antimicrob. Agents Chemother4513671373CrossRefPubMedGoogle Scholar
  69. Sabatini, LM, Azen, EA 1989Histatins, a family of salivary histidine-rich proteins, are encoded by at least two loci (HIS1 and HIS2)Biochem. Biophys. Res. Commun.160495502CrossRefPubMedGoogle Scholar
  70. Sajjan, US, Tran, LT, Sole, N, Rovaldi, C, Akiyama, A, Friden, PM, Forstner, JF, Rothstein, DM 2001P−113D, an antimicrobial peptide active against Pseudomonas aeruginosa, retains activity in the presence of sputum from cystic fibrosis patientsAntimicrob. Agents Chemother.4534373444CrossRefPubMedGoogle Scholar
  71. Schutte, BC, Mitros, JP, Bartlett, JA, Walters, JD, Jia, HP, Welsh, MJ, Casavant, TL, McCray, PB 2002Discovery of five conserved beta-defensin gene clusters using a computational search strategyProc. Natl. Acad. Sci. USA9921292133CrossRefPubMedGoogle Scholar
  72. Sorensen, OE, Borregaard, N 2005Cathelicidins–nature’s attempt at combinatorial chemistryComb. Chem. High Throughput Screen8273280CrossRefPubMedGoogle Scholar
  73. Territo, MC, Ganz, T, Selsted, ME, Lehrer, R 1989Monocyte-chemotactic activity of defensins from human neutrophilsJ. Clin. Invest.8420172020PubMedGoogle Scholar
  74. Tsai, H, Bobek, LA 1997Human salivary histatin−5 exerts potent fungicidal activity against Cryptococcus neoformansBiochim. Biophys. Acta1336367369PubMedGoogle Scholar
  75. Turner, J, Cho, Y, Dinh, NN, Waring, AJ, Lehrer, RI 1998Activities of LL−37, a cathelin-associated antimicrobial peptide of human neutrophilsAntimicrob. Agents Chemother.4222062214PubMedGoogle Scholar
  76. Dyke, T, Paquette, D, Grossi, S, Braman, V, Massaro, J, D’Agostino, R, Dibart, S, Friden, P 2002Clinical and microbial evaluation of a histatin-containing mouthrinse in humans with experimental gingivitis: a phase−2 multi-center studyJ. Clin. Periodontol.29168176CrossRefPubMedGoogle Scholar
  77. vanderSpek, JC, Wyandt, HE, Skare, JC, Milunsky, A, Oppenheim, FG, Troxler, RF 1989Localization of the genes for histatins to human chromosome 4q13 and tissue distribution of the mRNAsAm. J. Hum. Genet.45381387PubMedGoogle Scholar
  78. Veerman, EC, Nazmi, K, Van’t Hof, W, Bolscher, JG, Hertog, AL, Nieuw Amerongen, AV 2004Reactive oxygen species play no role in the candidacidal activity of the salivary antimicrobial peptide histatin 5Biochem. J.381447452CrossRefPubMedGoogle Scholar
  79. Velasco, M, Diaz-Guerra, MJ, Diaz-Achirica, P, Andreu, D, Rivas, L, Bosca, L 1997Macrophage triggering with cecropin A and melittin-derived peptides induces type II nitric oxide synthase expressionJ. Immunol.15844374443PubMedGoogle Scholar
  80. Horsten, HH, Derr, P, Kirchhoff, C 2002Novel antimicrobial peptide of human epididymal duct originBiol. Reprod67804813CrossRefPubMedGoogle Scholar
  81. Wang, Z, Wang, G 2004APD: the Antimicrobial Peptide DatabaseNucleic Acids Res.32D590 D592CrossRefPubMedGoogle Scholar
  82. White, SH, Wimley, WC, Selsted, ME 1995Structure, function, and membrane integration of defensinsCurr. Opin. Struct. Biol.5521527CrossRefPubMedGoogle Scholar
  83. Wunder, D, Dong, J, Baev, D, Edgerton, M 2004Human salivary histatin 5 fungicidal action does not induce programmed cell death pathways in Candida albicansAntimicrob. Agents Chemother.48110115CrossRefPubMedGoogle Scholar
  84. Yamaguchi, Y, Nagase, T, Makita, R, Fukuhara, S, Tomita, T, Tominaga, T, Kurihara, H, Ouchi, Y 2002Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and miceJ. Immunol.16925162523PubMedGoogle Scholar
  85. Yan, Q, Bennick, A 1995Identification of histatins as tannin-binding proteins in human salivaBiochem. J.311341347PubMedGoogle Scholar
  86. Yenugu, S, Hamil, KG, Radhakrishnan, Y, French, FS, Hall, SH 2004aThe androgen-regulated epididymal sperm-binding protein, human beta-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial beta-defensinEndocrinology14531653173CrossRefGoogle Scholar
  87. Yenugu, S, Hamil, KG, French, FS, Hall, SH 2004bAntimicrobial actions of the human epididymis 2 (HE2) protein isoforms, HE2alpha, HE2beta1 and HE2beta2Reprod. Biol. Endocrinol.261CrossRefGoogle Scholar
  88. Yoo, YC, Watanabe, R, Koike, Y, Mitobe, M, Shimazaki, K, Watanabe, S, Azuma, I 1997Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived peptide: involvement of reactive oxygen speciesBiochem. Biophys. Res. Commun.237624628CrossRefPubMedGoogle Scholar
  89. Zanetti, M 2004Cathelicidins, multifunctional peptides of the innate immunityJ. Leukoc. Biol.753948CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Unit of Fundamental and Applied Molecular Biology, Department for Molecular Biomedical ResearchGhent University and VIBGhentBelgium
  2. 2.Flen Pharma NVEdegemBelgium

Personalised recommendations