Chapter 2 : Defensins and Other Antimicrobial Peptides: Innate Defense of Mucosal Surfaces

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Defensins and Other Antimicrobial Peptides: Innate Defense of Mucosal Surfaces, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817619/9781555813239_Chap02-1.gif /docserver/preview/fulltext/10.1128/9781555817619/9781555813239_Chap02-2.gif


This chapter provides an in-depth account of defensins, and ties together the roles of other antimicrobial peptides and proteins that together contribute to mucosal innate host defense. While the focus is on defensins and antimicrobial peptides from humans, peptides from other species are also included where appropriate. The structural and functional relationships between these three classes of alpha-defensins, beta-defensins, theta-defensins are discussed in this chapter. The antibacterial and antifungal activities of the resulting retrocyclin were modest and were similar to those of synthetic and native rhesus theta-defensins. The noticeable salt sensitivity of ELR CXC chemokines was similar to that of defensins and many other antimicrobial peptides. High concentrations of alpha-defensins are frequently observed in chronically inflamed tissues. Certain factors within airway fluid, including electrolytes and anionic macromolecules, decrease the activity of many antimicrobial peptides, including defensins. Even though the processing of human neutrophil alpha-defensins occurs during neutrophil maturation prior to cellular release from the bone marrow, matrilysin may participate in the activation of beta-defensins or other antimicrobial peptides in the human airways. Defensins and other antimicrobial peptides and proteins coat mucosal surfaces and are among the primary early mediators of host defense against colonization and tissue invasion by pathogenic microbes. In vitro and in vivo studies indicate that most antimicrobial peptides probably act as endogenous antibiotics.

Citation: Cole A, Ganz T. 2005. Defensins and Other Antimicrobial Peptides: Innate Defense of Mucosal Surfaces, p 17-34. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch2

Key Concept Ranking

Bacterial Proteins
Two-Component Signal Transduction Systems
Nuclear Magnetic Resonance Spectroscopy
Herpes simplex virus 1
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Agerberth, B.,, J. Charo,, J. Werr,, B. Olsson,, F. Idali,, L. Lindbom,, R. Kiessling,, H. Jornvall,, H. Wigzell,, and G. H. Gudmundsson. 2000. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96:30863093.
2. Agerberth, B.,, H. Gunne,, J. Odeberg,, P. Kogner,, H. G. Boman,, and G. H. Gudmundsson. 1995. FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proc. Natl. Acad. Sci. USA 92:195199.
3. Agerberth, B.,, J. Y. Lee,, T. Bergman,, M. Carlquist,, H. G. Boman,, V. Mutt,, and H. Jornvall. 1991. Amino acid sequence of PR-39. Isolation from pig intestine of a new member of the family of proline-arginine-rich antibacterial peptides. Eur. J. Biochem. 202:849854.
4. Aho, H. J.,, R. Grenman,, J. Sipila,, H. Peuravuori,, J. Hartikainen,, and T. J. Nevalainen. 1997. Group II phospholipase A2 in nasal fluid, mucosa and paranasal sinuses. Acta Otolaryngol. 117:860863.
5. Akinbi, H. T.,, R. Epaud,, H. Bhatt,, and T. E. Weaver. 2000. Bacterial killing is enhanced by expression of lysozyme in the lungs of transgenic mice. J. Immunol. 165:57605766.
6. Alcouloumre, M. S.,, M. A. Ghannoum,, A. S. Ibrahim,, M. E. Selsted,, and J. E. J. Edwards. 1993. Fungicidal properties of defensin NP-1 and activity against Cryptococcus neoformans in vitro. Antimicrob. Agents Chemother. 37:26282632.
7. Aley, S. B.,, M. Zimmerman,, M. Hetsko,, M. E. Selsted,, and F. D. Gillin. 1994. Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides. Infect. Immun. 62:53975403.
8. Andersen, J. H.,, S. A. Osbakk,, L. H. Vorland,, T. Traavik,, and T. J. Gutteberg. 2001. Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts. Antiviral Res. 51:141149.
9. Andreu, D.,, and L. Rivas. 1998. Animal antimicrobial peptides: an overview. Biopolymers 47:415433.
10. Arnold, R. R.,, J. E. Russell,, W. J. Champion,, M. Brewer,, and J. J. Gauthier. 1982. Bactericidal activity of human lactoferrin: differentiation from the stasis of iron deprivation. Infect. Immun. 35:792799.
11. Aumelas, A.,, M. Mangoni,, C. Roumestand,, L. Chiche,, E. Despaux,, G. Grassy,, B. Calas,, and A. Chavanieu. 1996. Synthesis and solution structure of the antimicrobial peptide protegrin-1. Eur. J. Biochem. 237:575583.
12. Ayabe, T.,, D. P. Satchell,, C. L. Wilson,, W. C. Parks,, M. E. Selsted,, and A. J. Ouellette. 2000. Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1:113118.
13. Bals, R. 2000. Epithelial antimicrobial peptides in host defense against infection. Respir. Res. 1:141150.
14. Bals, R.,, X. Wang,, M. Zasloff,, and J. M. Wilson. 1998. The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc. Natl. Acad. Sci. USA 95:95419546.
15. Bals, R.,, D. J. Weiner,, R. L. Meegalla,, F. Accurso,, and J. M. Wilson. 2001. Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid. Am. J. Respir. Cell Mol. Biol. 25:2125.
16. Bateman, A.,, R. J. MacLeod,, P. Lembessis,, J. Hu,, F. Esch,, and S. Solomon. 1996. The isolation and characterization of a novel corticostatin/defensin-like peptide from the kidney. J. Biol. Chem. 271:1065410659.
17. Becker, M. N.,, G. Diamond,, M. W. Verghese,, and S. H. Randell. 2000. CD14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human tracheobronchial epithelium. J. Biol. Chem. 275:2973129736.
18. Bellamy, W.,, M. Takase,, H. Wakabayashi,, K. Kawase,, and M. Tomita. 1992. Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin. J. Appl. Bacteriol. 73:472479.
19. Bensch, K. W.,, M. Raida,, H. J. Magert,, P. Schulz-Knappe,, and W. G. Forssmann. 1995. hBD-1: a novel beta-defensin from human plasma. FEBS Lett. 368:331335.
20. Billiau, A., and K. Vandenbroeck,. 2000. IFN-γ, p. 641688. In J. J. Oppenheim,, M. Feldmann,, S. K. Duram,, T. Hirano,, J. Vilcek,, and N. A. Nicola (ed.), Cytokine Reference. A Compendium of Cytokines and Other Mediators of Host Defense. Academic Press, Inc., New York, N.Y.
21. Bingle, C. D.,, and C. J. Craven. 2002. PLUNC: a novel family of candidate host defence proteins expressed in the upper airways and nasopharynx. Hum. Mol. Genet. 11:937943.
22. Biragyn, A.,, P. A. Ruffini,, C. A. Leifer,, E. Klyushnenkova,, A. Shakhov,, O. Chertov,, A. K. Shirakawa,, J. M. Farber,, D. M. Segal,, J. J. Oppenheim,, and L. W. Kwak. 2002. Tolllike receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298:10251029.
23. Biragyn, A.,, M. Surenhu,, D. Yang,, P. A. Ruffini,, B. A. Haines,, E. Klyushnenkova,, J. J. Oppenheim,, and L. W. Kwak. 2001. Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens. J. Immunol. 167:66446653.
24. Birchler, T.,, R. Seibl,, K. Buchner,, S. Loeliger,, R. Seger,, J. P. Hossle,, A. Aguzzi,, and R. P. Lauener. 2001. Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein. Eur. J. Immunol. 31:31313137.
25. Boman, H. G. 1995. Peptide antibiotics and their role in innate immunity. Annu. Rev. Immunol. 13:6192.
26. 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. A 371A:201206.
27. Brogden, K. A.,, M. Ackermann,, and K. M. Huttner. 1998. Detection of anionic antimicrobial peptides in ovine bronchoalveolar lavage fluid and respiratory epithelium. Infect. Immun. 66:59485954.
28. Brogden, K. A.,, M. R. Ackermann,, P. B. McCray, Jr.,, and K. M. Huttner. 1999. Differences in the concentrations of small, anionic, antimicrobial peptides in bronchoalveolar lavage fluid and in respiratory epithelia of patients with and without cystic fibrosis. Infect. Immun. 67:42564259.
29. Bullen, J. J.,, and J. A. Armstrong. 1979. The role of lactoferrin in the bactericidal function of polymorphonuclear leucocytes. Immunology 36:781791.
30. Canny, G.,, O. Levy,, G. T. Furuta,, S. Narravula-Alipati,, R. B. Sisson,, C. N. Serhan,, and S. P. Colgan. 2002. Lipid mediatorinduced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia. Proc. Natl. Acad. Sci. USA 99:39023907.
31. Chang, T. L.,, F. Francois,, A. Mosoian,, and M. E. Klotman. 2003. CAF-mediated human immunodeficiency virus (HIV) type 1 transcriptional inhibition is distinct from alphadefensin- 1 HIV inhibition. J. Virol. 77:67776784.
32. Chapple, D. S.,, C. L. Joannou,, D. J. Mason,, J. K. Shergill,, E. W. Odell,, V. Gant,, and R. W. Evans. 1998. A helical region on human lactoferrin. Its role in antibacterial pathogenesis. Adv. Exp. Med. Biol. 443:215220.
33. Chen, F. Y.,, M. T. Lee,, and H. W. Huang. 2003. Evidence for membrane thinning effect as the mechanism for peptideinduced pore formation. Biophys. J. 84:37513758.
34. Chertov, O.,, D. F. Michiel,, L. Xu,, J. M. Wang,, K. Tani,, W. J. Murphy,, D. L. Longo,, D. D. Taub,, and J. J. Oppenheim. 1996. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J. Biol. Chem. 271:29352940.
35. Clohessy, P. A.,, and B. E. Golden. 1996. The mechanism of calprotectin’s candidastatic activity appears to involve zinc chelation. Biochem. Soc. Trans. 24:309S.
36. Cohen, J. 2002. AIDS Research: mystery anti-HIV factor unmasked? Science 297:2188.
37. Cole, A. M.,, P. Dewan,, and T. Ganz. 1999. Innate antimicrobial activity of nasal secretions. Infect. Immun. 67:32673275.
38. Cole, A. M.,, T. Ganz,, A. M. Liese,, M. D. Burdick,, L. Liu,, and R. M. Strieter. 2001. Cutting edge: IFN-inducible ELR- CXC chemokines display defensin-like antimicrobial activity. J. Immunol. 167:623627.
39. Cole, A. M.,, T. Hong,, L. M. Boo,, T. Nguyen,, C. Zhao,, G. Bristol,, J. A. Zack,, A. J. Waring,, O. O. Yang,, and R. I. Lehrer. 2002. Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc. Natl. Acad. Sci. USA 99:18131818.
40. Cole, A. M.,, Y. H. Kim,, S. Tahk,, T. Hong,, P. Weis,, A. J. Waring,, and T. Ganz. 2001. Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett. 504:510.
41. Cole, A. M.,, H. I. Liao,, O. Stuchlik,, J. Tilan,, J. Pohl,, and T. Ganz. 2002. Cationic polypeptides are required for antibacterial activity of human airway fluid. J. Immunol. 169:69856991.
42. 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.
43. Cowland, J. B.,, A. H. Johnsen,, and N. Borregaard. 1995. hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett. 368:173176.
44. Daher, K. A.,, M. E. Selsted,, and R. I. Lehrer. 1986. Direct inactivation of viruses by human granulocyte defensins. J. Virol. 60:10681074.
45. Diamond, G.,, M. Zasloff,, H. Eck,, M. Brasseur,, W. L. Maloy,, and C. L. Bevins. 1991. Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc. Natl. Acad. Sci. USA 88:39523956.
46. Dorschner, R. A.,, V. K. Pestonjamasp,, S. Tamakuwala,, T. Ohtake,, J. Rudisill,, V. Nizet,, B. Agerberth,, G. H. Gudmundsson,, and R. L. Gallo. 2001. Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J. Investig. Dermatol. 117:9197.
47. Duits, L. A.,, P. H. Nibbering,, E. van Strijen,, J. B. Vos,, S. P. Mannesse-Lazeroms,, M. A. van Sterkenburg,, and P. S. Hiemstra. 2003. Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells. FEMS Immunol. Med. Microbiol. 38:5964.
48. Duits, L. A.,, B. Ravensbergen,, M. Rademaker,, P. S. Hiemstra,, and P. H. Nibbering. 2002. Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106:517525.
49. Dunsmore, S. E.,, U. K. Saarialho-Kere,, J. D. Roby,, C. L. Wilson,, L. M. Matrisian,, H. G. Welgus,, and W. C. Parks. 1998. Matrilysin expression and function in airway epithelium. J. Clin. Investig. 102:13211331.
50. Edgerton, M.,, and S. E. Koshlukova. 2000. Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva. Adv. Dent. Res. 14:1621.
51. Ellison, R. T., III,, and T. J. Giehl. 1991. Killing of Gramnegative bacteria by lactoferrin and lysozyme. J. Clin. Investig. 88:10801091.
52. Elsbach, P.,, and J. Weiss. 1993. The bactericidal/permeability- increasing protein (BPI), a potent element in host-defense against gram-negative bacteria and lipopolysaccharide. Immunobiology 187:417429.
53. Ernst, R. K.,, T. Guina,, and S. I. Miller. 2001. Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity. Microbes Infect. 3:13271334.
54. Fahrner, R. l.,, T. Dieckmann,, S. S. Harwig,, R. I. Lehrer,, D. Eisenberg,, and J. Feigon. 1996. Solution structure of protegrin- 1, a broad-spectrum antimicrobial peptide from porcine leukocytes. Chem. Biol. 3:543550.
55. Fellermann, K.,, J. Wehkamp,, K. R. Herrlinger,, and E. F. Stange. 2003. Crohn’s disease: a defensin deficiency syndrome? Eur. J. Gastroenterol. Hepatol. 15:627634.
56. Fleming, A. 1922. On a remarkable bacteriolytic element found in tissues and secretions. Proc. R. Soc. Lond. Ser. B 93:306317.
57. Forst, S.,, J. Weiss,, J. M. Maraganore,, R. L. Heinrikson,, and P. Elsbach. 1987. Relation between binding and the action of phospholipases A2 on Escherichia coli exposed to the bactericidal/ permeability-increasing protein of neutrophils. Biochim. Biophys. Acta 920:221225.
58. Gallo, R. L.,, K. J. Kim,, M. Bernfield,, C. A. Kozak,, M. Zanetti,, L. Merluzzi,, and R. Gennaro. 1997. Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse. J. Biol. Chem. 272:1308813093.
59. Ganz, T. 1999. Defensins and host defense. Science 286:420421.
60. Ganz, T. 2001. Defensins in the urinary tract and other tissues. J. Infect. Dis. 183(Suppl. 1):S41S42.
61. Ganz, T.,, V. Gabayan,, H. I. Liao,, L. Liu,, A. Oren,, T. Graf,, and A. M. Cole. 2002. Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan. Blood 101:23882392.
62. Ganz, T.,, and R. I. Lehrer. 1994. Defensins. Curr. Opin. Immunol. 6:584589.
63. Ganz, T.,, and R. I. Lehrer. 1997. Antimicrobial peptides of leukocytes. Curr. Opin. Hematol. 4:5358.
64. 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. Investig. 82:552556.
65. Ganz, T.,, M. E. Selsted,, D. Szklarek,, S. S. Harwig,, K. Daher,, D. F. Bainton,, and R. I. Lehrer. 1985. Defensins. Natural peptide antibiotics of human neutrophils. J. Clin. Investig. 76:14271435.
66. Garcia, J. R.,, F. Jaumann,, S. Schulz,, A. Krause,, J. Rodriguez- Jimenez,, U. Forssmann,, K. Adermann,, E. Kluver,, C. Vogelmeier,, D. Becker,, R. Hedrich,, W. G. Forssmann,, and R. Bals. 2001. Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res. 306:257264.
67. Gazit, E.,, I. R. Miller,, P. C. Biggin,, M. S. Sansom,, and Y. Shai. 1996. Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. J. Mol. Biol. 258:860870.
68. Ghosh, D.,, E. Porter,, B. Shen,, S. K. Lee,, D. Wilk,, J. Drazba,, S. P. Yadav,, J. W. Crabb,, T. Ganz,, and C. L. Bevins. 2002. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat. Immunol. 3:583590.
69. Goldman, M.,, G. Anderson,, E. D. Stolzenberg,, U. P. Kari,, M. Zasloff,, and J. M. Wilson. 1997. Human β-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88:553560.
70. Gombart, A. F.,, M. Shiohara,, S. H. Kwok,, K. Agematsu,, A. Komiyama,, and H. P. Koeffler. 2001. Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein-epsilon. Blood 97:25612567.
71. Gregory, R. J.,, S. H. Cheng,, D. P. Rich,, J. Marshall,, S. Paul,, K. Hehir,, L. Ostedgaard,, K. W. Klinger,, M. J. Welsh,, and A. E. Smith. 1990. Expression and characterization of the cystic fibrosis transmembrane conductance regulator. Nature 347:382386.
72. Groisman, E. A. 2001. The pleiotropic two-component regulatory system PhoP-PhoQ. J. Bacteriol. 183:18351842.
73. 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.
74. Gudmundsson, G. H.,, and B. Agerberth. 1999. Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system. J. Immunol. Methods 232:4554.
75. Hancock, R. E. 1997. Peptide antibiotics. Lancet 349:418422.
76. Hancock, R. E.,, and A. Patrzykat. 2002. Clinical development of cationic antimicrobial peptides: from natural to novel antibiotics. Curr. Drug Targets Infect. Disord. 2:7983.
77. Harder, J.,, J. Bartels,, E. Christophers,, and J. M. Schroder. 2001. Isolation and characterization of human beta-defensin- 3, a novel human inducible peptide antibiotic. J. Biol. Chem. 276:57075713.
78. Harder, J.,, J. Bartels,, E. Christophers,, and J.-M. Schroeder. 1997. A peptide antibiotic from human skin. Nature 387:861862.
79. Harmsen, M. C.,, P. J. Swart,, M. P. de Bethune,, R. Pauwels,, E. De Clercq,, T. H. The,, and D. K. Meijer. 1995. Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J. Infect. Dis. 172:380388.
80. Harwig, S. S.,, V. N. Kokryakov,, K. M. Swiderek,, G. M. Aleshina,, C. Zhao,, and R. I. Lehrer. 1995. Prophenin-1, an exceptionally proline-rich antimicrobial peptide from porcine leukocytes. FEBS Lett. 362:6569.
81. Harwig, S. S.,, A. S. Park,, and R. I. Lehrer. 1992. Characterization of defensin precursors in mature human neutrophils. Blood 79:15321537.
82. Harwig, S. S. L.,, X.-D. Qu,, L. Tan,, and R. I. Lehrer. 1994. Small intestinal Paneth cells contain a potently antimicrobial group II phospholipase A-2. FASEB J. 8:A516.
83. Hasegawa, K.,, W. Motsuchi,, S. Tanaka,, and S. Dosako. 1994. Inhibition with lactoferrin of in vitro infection with human herpes virus. Jpn. J. Med. Sci. Biol. 47:7385.
84. Hein, M.,, E. V. Valore,, R. B. Helmig,, N. Uldbjerg,, and T. Ganz. 2002. Antimicrobial factors in the cervical mucus plug. Am. J. Obstet. Gynecol. 187:137144.
85. Hertz, C. J.,, Q. Wu,, E. M. Porter,, Y. J. Zhang,, K. H. Weismuller,, P. J. Godowski,, T. Ganz,, S. H. Randell,, and R. L. Modlin. 2003. Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J. Immunol. 171:68206826.
86. Hiemstra, P. S.,, R. J. Maassen,, J. Stolk,, R. Heinzel-Wieland,, G. J. Steffens,, and J. H. Dijkman. 1996. Antibacterial activity of antileukoprotease. Infect. Immun. 64:45204524.
87. Higazi, A. A.,, I. I. Barghouti,, and R. Abu-Much. 1995. Identification of an inhibitor of tissue-type plasminogen activatormediated fibrinolysis in human neutrophils. A role for defensin. J. Biol. Chem. 270:94729477.
88. Higazi, A. A. R.,, T. Ganz,, K. Kariko,, and D. B. Cines. 1996. Defensin modulates tissue-type plasminogen activator and plasminogen binding to fibrin and endothelial cells. J. Biol. Chem. 271:1765017655.
89. Hill, C. P.,, J. Yee,, M. E. Selsted,, and D. Eisenberg. 1991. Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science 251:14811485.
90. Hiratsuka, T.,, M. Nakazato,, Y. Date,, J. Ashitani,, T. Minematsu,, N. Chino,, and S. Matsukura. 1998. Identification of human beta-defensin-2 in respiratory tract and plasma and its increase in bacterial pneumonia. Biochem. Biophys. Res. Commun. 249:943947.
91. Hobbs, J. A.,, R. May,, K. Tanousis,, E. McNeill,, M. Mathies,, C. Gebhardt,, R. Henderson,, M. J. Robinson,, and N. Hogg. 2003. Myeloid cell function in MRP-14 (S100A9) null mice. Mol. Cell. Biol. 23:25642576.
92. Hoover, D. M.,, C. Boulegue,, D. Yang,, J. J. Oppenheim,, K. Tucker,, W. Lu,, and J. Lubkowski. 2002. The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins. J. Biol. Chem. 277:3764737654.
93. Hoover, D. M.,, O. Chertov,, and J. Lubkowski. 2001. The structure of human beta-defensin-1: new insights into structural properties of beta-defensins. J. Biol. Chem. 276:3902139026.
94. Hoover, D. M.,, K. R. Rajashankar,, R. Blumenthal,, A. Puri,, J. J. Oppenheim,, O. Chertov,, and J. Lubkowski. 2000. The structure of human beta-defensin-2 shows evidence of higher order oligomerization. J. Biol. Chem. 275:3291132918.
95. Hughes, A. L. 1999. Evolutionary diversification of the mammalian defensins. Cell Mol. Life Sci. 56:94103.
96. Ibrahim, H. R.,, T. Matsuzaki,, and T. Aoki. 2001. Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function. FEBS Lett. 506:2732.
97. Islam, D.,, L. Bandholtz,, J. Nilsson,, H. Wigzell,, B. Christensson,, B. Agerberth,, and G. Gudmundsson. 2001. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat. Med. 7:180185.
98. Janeway, C. A., Jr.,, and R. Medzhitov. 2002. Innate immune recognition. Annu. Rev. Immunol. 20:197216.
99. Johansson, J.,, G. H. Gudmundsson,, M. E. Rottenberg,, K. D. Berndt,, and B. Agerberth. 1998. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J. Biol. Chem. 273:37183724.
100. Joiner, K. A.,, T. Ganz,, J. Albert,, and D. Rotrosen. 1989. The opsonizing ligand on Salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes. J. Cell Biol. 109:27712782.
101. Jones, D. E.,, and C. L. Bevins. 1992. Paneth cells of the human small intestine express an antimicrobial peptide gene. J. Biol. Chem. 267:2321623225.
102. Jones, D. E.,, and C. L. Bevins. 1993. Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett. 315:187192.
103. Kalfa, V. C.,, and K. A. Brogden. 1999. Anionic antimicrobial peptide-lysozyme interactions in innate pulmonary immunity. Int. J. Antimicrob. Agents 13:4751.
104. Kaliner, M. A. 1991. Human nasal respiratory secretions and host defense. Am. Rev. Respir. Dis. 144:S52S56.
105. Kaliner, M. A. 1992. Human nasal host defense and sinusitis. J. Allergy Clin. Immunol. 90:424430.
106. Knowles, M. R.,, J. M. Robinson,, R. E. Wood,, C. A. Pue,, W. M. Mentz,, G. C. Wager,, J. T. Gatzy,, and R. C. Boucher. 1997. Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and diseasecontrol subjects. J. Clin. Investig. 100:25882595.
107. Kokryakov, V. N.,, S. S. Harwig,, E. A. Panyutich,, A. A. Shevchenko,, G. M. Aleshina,, O. V. Shamova,, H. A. Korneva,, and R. I. Lehrer. 1993. Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins. FEBS Lett. 327:231236.
108. LaBranche, C. C.,, G. Galasso,, J. P. Moore,, D. P. Bolognesi,, M. S. Hirsch,, and S. M. Hammer. 2001. HIV fusion and its inhibition. Antiviral Res. 50:95115.
109. Laible, N. J.,, and G. R. Germaine. 1985. Bactericidal activity of human lysozyme, muramidase-inactive lysozyme, and cationic polypeptides against Streptococcus sanguis and Streptococcus faecalis: inhibition by chitin oligosaccharides. Infect. Immun. 48:720728.
110. Larrick, J. W.,, M. Hirata,, R. F. Balint,, J. Lee,, J. Zhong,, and S. C. Wright. 1995. Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect. Immun. 63:12911297.
111. Lauw, F. N.,, A. J. H. Simpson,, J. M. Prins,, S. J. H. van Deventer,, W. Chaowagul,, N. J. White,, and T. van der Poll. 2000. The CXC chemokines gamma interferon (IFN-γ)-inducible protein 10 and monokine induced by IFN-γ are released during severe melioidosis. Infect. Immun. 68:38883893.
112. Lawrance, I. C.,, C. Fiocchi,, and S. Chakravarti. 2001. Ulcerative colitis and Crohn’s disease: distinctive gene expression profiles and novel susceptibility candidate genes. Hum. Mol. Genet. 10:445456.
113. Lee-Huang, S.,, P. L. Huang,, Y. Sun,, P. L. Huang,, H. F. Kung,, D. L. Blithe,, and H. C. Chen. 1999. Lysozyme and RNases as anti-HIV components in beta-core preparations of human chorionic gonadotropin. Proc. Natl. Acad. Sci. USA 96:26782681.
114. Lehrer, R. I.,, A. Barton,, K. A. Daher,, S. S. Harwig,, T. Ganz,, and M. E. Selsted. 1989. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J. Clin. Investig. 84:553561.
115. Lehrer, R. I.,, C. L. Bevins,, and T. Ganz,. 1999. Defensins and other antimicrobial peptides, p. 8999. In P. L. Ogra,, J. Mestecky,, M. E. Lamm,, W. Strober,, J. Bienenstock,, and J. R. McGhee (ed.), Mucosal Immunology Academic Press, Inc., San Diego, Calif.
116. Lehrer, R. I.,, K. Daher,, T. Ganz,, and M. E. Selsted. 1985. Direct inactivation of viruses by MCP-1 and MCP-2, natural peptide antibiotics from rabbit leukocytes. J. Virol. 54:467472.
117. Lehrer, R. I.,, and T. Ganz. 2002. Defensins of vertebrate animals. Curr. Opin. Immunol. 14:96102.
118.. Lehrer, R. I.,, T. Ganz,, D. Szklarek,, and M. E. Selsted. 1988. Modulation of the in vitro candidacidal activity of human neutrophil defensins by target cell metabolism and divalent cations. J. Clin. Investig. 81:18291835.
119. Lehrer, R. I.,, D. Szklarek,, T. Ganz,, and M. E. Selsted. 1985. Correlation of binding of rabbit granulocyte peptides to Candida albicans with candidacidal activity. Infect. Immun. 49:207211.
120. Leonova, L.,, V. N. Kokryakov,, G. M. Aleshina,, T. Hong,, T. Nguyen,, C. Zhao,, A. J. Waring,, and R. I. Lehrer. 2001. Circular minidefensins and posttranslational generation of molecular diversity. J. Leukoc. Biol. 70:461464.
121. Levy, J. A. 2001. The importance of the innate immune system in controlling HIV infection and disease. Trends Immunol. 22:312316.
122. Levy, O.,, S. Martin,, E. Eichenwald,, T. Ganz,, E. Valore,, S. F. Carroll,, K. Lee,, D. Goldmann,, and G. M. Thorne. 1999. Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein. Pediatrics 104:13271333.
123. Lillard, J. W., Jr.,, P. N. Boyaka,, O. Chertov,, J. J. Oppenheim,, and J. R. McGhee. 1999. Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc. Natl. Acad. Sci. USA 96:651656.
124. Liu, L.,, C. Zhao,, H. H. Q. Heng,, and T. Ganz. 1997. The human β-defensin-1 and α-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry. Genomics 43:316320.
125. Lomax, K. J.,, J. I. Gallin,, D. Rotrosen,, G. D. Raphael,, M. A. Kaliner,, E. J. Jr. Benz, L. A. Boxer, and H. L. Malech. 1989. Selective defect in myeloid cell lactoferrin gene expression in neutrophil specific granule deficiency. J. Clin. Investig. 83:514519.
126. Ludtke, S. J.,, K. He,, W. T. Heller,, T. A. Harroun,, L. Yang,, and H. W. Huang. 1996. Membrane pores induced by magainin. Biochemistry 35:1372313728.
127. Mackewicz, C. E.,, J. Yuan,, P. Tran,, L. Diaz,, E. Mack,, M. E. Selsted,, and J. A. Levy. 2003. α-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS 17:F23F32.
128. MacLeod, R. J.,, J. R. Hamilton,, A. Bateman,, D. Belcourt,, J. Hu,, H. P. Bennett,, and S. Solomon. 1991. Corticostatic peptides cause nifedipine-sensitive volume reduction in jejunal villus enterocytes. Proc. Natl. Acad. Sci. USA 88:552556.
129. Mangoni, M. E.,, A. Aumelas,, P. Charnet,, C. Roumestand,, L. Chiche,, E. Despaux,, G. Grassy,, B. Calas,, and A. Chavanieu. 1996. Change in membrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation. FEBS Lett. 383:9398.
130. 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.
131. Martin, E.,, T. Ganz,, and R. I. Lehrer. 1995. Defensins and other endogenous peptide antibiotics of vertebrates. J. Leukoc. Biol. 58:128136.
132. Mathews, M.,, H. P. Jia,, J. M. Guthmiller,, G. Losh,, S. Graham,, G. K. Johnson,, B. F. Tack,, and P. B. McCray, Jr. 1999. Production of b-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect. Immun. 67:27402745.
133. Matsui, H.,, B. R. Grubb,, R. Tarran,, S. H. Randell,, J. T. Gatzy,, C. W. Davis,, and R. C. Boucher. 1998. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95:10051015.
134. Matsuzaki, K. 2001. Why and how are peptide-lipid interactions utilized for self defence? Biochem. Soc. Trans. 29:598601.
135. Maxwell, A. I.,, G. M. Morrison,, and J. R. Dorin. 2003. Rapid sequence divergence in mammalian beta-defensins by adaptive evolution. Mol. Immunol. 40:413421.
136. McCray, P. B.,, and L. Bentley. 1997. Human airway epithelia express a β-defensin. Am. J. Respir. Cell Mol. Biol. 16:343349.
137. Meredith, S. D.,, G. D. Raphael,, J. N. Baraniuk,, S. M. Banks,, and M. A. Kaliner. 1989. The pathophysiology of rhinitis. III. The control of IgG secretion. J. Allergy Clin. Immunol. 84:920930.
138. Milner, S. M.,, and M. R. Ortega. 1999. Reduced antimicrobial peptide expression in human burn wounds. Burns 25:411413.
139. Miyasaki, K. T.,, A. L. Bodeau,, T. Ganz,, M. E. Selsted,, and R. I. Lehrer. 1990. In vitro sensitivity of oral, gram-negative, facultative bacteria to the bactericidal activity of human neutrophil defensins. Infect. Immun. 58:39343940.
140. Monell, C. R.,, and M. Strand. 1994. Structural and functional similarities between synthetic HIV gp41 peptides and defensins. Clin. Immunol. Immunopathol. 71:315324.
141. Morrison, G. M.,, D. J. Davidson,, and J. R. Dorin. 1999. A novel mouse beta defensin, Defb2, which is upregulated in the airways by lipopolysaccharide. FEBS Lett. 442:112116.
142. Münk, C.,, G. Wei,, O. O. Yang,, A. J. Waring,, W. Wang,, T. Hong,, R. I. Lehrer,, N. R. Landau,, and A. M. Cole. 2003. The theta-defensin, retrocyclin, inhibits HIV-1 entry. AIDS Res. Hum. Retroviruses 19:875881.
143. Murphy, C. J.,, B. A. Foster,, M. J. Mannis,, M. E. Selsted,, and T. W. Reid. 1993. Defensins are mitogenic for epithelial cells and fibroblasts. J. Cell. Physiol. 155:408413.
144. Nevalainen, T. J.,, H. J. Aho,, and H. Peuravuori. 1994. Secretion of group 2 phospholipase A2 by lacrimal glands. Investig. Ophthalmol. Visual Sci. 35:417421.
145. Nguyen, T. X.,, A. M. Cole,, and R. I. Lehrer. 2003. Evolution of primate theta-defensins: a serpentine path to a sweet tooth. Peptides 24:16471654.
146. Niyonsaba, F.,, K. Iwabuchi,, H. Matsuda,, H. Ogawa,, and I. Nagaoka. 2002. Epithelial cell-derived human betadefensin- 2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int. Immunol. 14:421426.
147. Niyonsaba, F.,, A. Someya,, M. Hirata,, H. Ogawa,, and I. Nagaoka. 2001. Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Eur. J. Immunol. 31:10661075.
148. Nizet, V.,, T. Ohtake,, X. Lauth,, J. Trowbridge,, J. Rudisill,, R. A. Dorschner,, V. Pestonjamasp,, J. Piraino,, K. Huttner,, and R. L. Gallo. 2001. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414:454457.
149. Ogata, K.,, B. A. Linzer,, R. I. Zuberi,, T. Ganz,, R. I. Lehrer,, and A. Catanzaro. 1992. Activity of defensins from human neutrophilic granulocytes against Mycobacterium avium- Mycobacterium intracellulare. Infect. Immun. 60:47204725.
150. O’Neil, D. A.,, E. M. Porter,, D. Elewaut,, G. M. Anderson,, L. Eckmann,, T. Ganz,, and M. F. Kagnoff. 1999. Expression and regulation of the human beta-defensins hBD-1 and hBD- 2 in intestinal epithelium. J. Immunol. 163:67186724.
151. Oppenheim, F. G.,, T. Xu,, F. M. McMillian,, S. M. Levitz,, R. D. Diamond,, G. D. Offner,, and R. F. Troxler. 1988. Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. J. Biol. Chem. 263:74727477.
152. Oren, A.,, T. Ganz,, L. Liu,, and T. Meerloo. 2003. In human epidermis, [beta]-defensin 2 is packaged in lamellar bodies. Exp. Mol. Pathol. 74:180182.
153. Ortega, M. R.,, T. Ganz,, and S. M. Milner. 2000. Human beta defensin is absent in burn blister fluid. Burns 26:724726.
154. Ouellette, A. J.,, and C. L. Bevins. 2001. Paneth cell defensins and innate immunity of the small bowel. Inflamm. Bowel Dis. 7:4350.
155. Ouellette, A. J.,, and M. E. Selsted. 1996. Paneth cell defensins: endogenous peptide components of intestinal host defense. FASEB J. 10:12801289.
156. Panyutich, A.,, and T. Ganz. 1991. Activated alpha 2-macroglobulin is a principal defensin-binding protein. Am. J. Respir. Cell Mol. Biol. 5:101106.
157. Panyutich, A.,, J. Shi,, P. L. Boutz,, C. Zhao,, and T. Ganz. 1997. Porcine polymorphonuclear leukocytes generate extracellular microbicidal activity by elastase-mediated activation of secreted proprotegrins. Infect. Immun. 65:978985.
158. Panyutich, A. V.,, P. S. Hiemstra,, S. Van Wetering,, and T. Ganz. 1995. Human neutrophil defensin and serpins form complexes and inactivate each other. Am. J. Respir. Cell Mol. Biol. 12:351357.
159. Panyutich, A. V.,, O. Szold,, P. H. Poon,, Y. Tseng,, and T. Ganz. 1994. Identification of defensin binding to C1 complement. FEBS Lett. 356:169173.
160. Perez-Canadillas, J. M.,, A. Zaballos,, J. Gutierrez,, R. Varona,, F. Roncal,, J. P. Albar,, G. Marquez,, and M. Bruix. 2001. NMR solution structure of murine CCL20/MIP-3alpha, a chemokine that specifically chemoattracts immature dendritic cells and lymphocytes through its highly specific interaction with the beta-chemokine receptor CCR6. J. Biol. Chem. 276:2837228379.
161. Peschel, A.,, R. W. Jack,, M. Otto,, L. V. Collins,, P. Staubitz,, G. Nicholson,, H. Kalbacher,, W. F. Nieuwenhuizen,, G. Jung,, A. Tarkowski,, K. P. van Kessel,, and J. A. van Strijp. 2001. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J. Exp. Med. 193:10671076.
162. Peschel, A.,, M. Otto,, R. W. Jack,, H. Kalbacher,, G. Jung,, and F. Gotz. 1999. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J. Biol. Chem. 274:84058410.
163. Pestonjamasp, V. K.,, K. H. Huttner,, and R. L. Gallo. 2001. Processing site and gene structure for the murine antimicrobial peptide CRAMP. Peptides 22:16431650.
164. Puddu, P.,, P. Borghi,, S. Gessani,, P. Valenti,, F. Belardelli,, and L. Seganti. 1998. Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection. Int. J. Biochem. Cell Biol. 30:10551062.
165. Qu, X. D.,, K. C. Lloyd,, J. H. Walsh,, and R. I. Lehrer. 1996. Secretion of type II phospholipase A2 and cryptdin by rat small intestinal Paneth cells. Infect. Immun. 64:51615165.
166. Quinones-Mateu, M. E.,, M. M. Lederman,, Z. Feng,, B. Chakraborty,, J. Weber,, H. R. Rangel,, M. L. Marotta,, M. Mirza,, B. Jiang,, P. Kiser,, K. Medvik,, S. F. Sieg,, and A. Weinberg. 2003. Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS 17:F39F48.
167. Raphael, G. D.,, J. L. Davis,, P. C. Fox,, H. L. Malech,, J. I. Gallin,, J. N. Baraniuk,, and M. A. Kaliner. 1989. Glandular secretion of lactoferrin in a patient with neutrophil lactoferrin deficiency. J. Allergy Clin. Immunol. 84:914919.
168. Raphael, G. D.,, E. V. Jeney,, J. N. Baraniuk,, I. Kim,, S. D. Meredith,, and M. A. Kaliner. 1989. Pathophysiology of rhinitis. Lactoferrin and lysozyme in nasal secretions. J. Clin. Investig. 84:15281535.
169. Revenis, M. E.,, and M. A. Kaliner. 1992. Lactoferrin and lysozyme deficiency in airway secretions: association with the development of bronchopulmonary dysplasia. J. Pediatr. 121:262270.
170. Rothenberg, R. B.,, M. Scarlett,, C. del Rio,, D. Reznik,, and C. O’Daniels. 1998. Oral transmission of HIV. AIDS 12:20952105.
171. Salzman, N. H.,, D. Ghosh,, K. M. Huttner,, Y. Paterson,, and C. L. Bevins. 2003. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422:522526.
172. Samaranayake, Y. H.,, L. P. Samaranayake,, P. C. Wu,, and M. So. 1997. The antifungal effect of lactoferrin and lysozyme on Candida krusei and Candida albicans. APMIS 105:875883.
173. Satoh, Y. 1988. Effect of live and heat-killed bacteria on the secretory activity of Paneth cells in germ-free mice. Cell Tissue Res. 251:8793.
174. Satoh, Y.,, K. Ishikawa,, Y. Oomori,, S. Takeda,, and K. Ono. 1992. Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells of mouse intestine. Cell Tissue Res. 269:213220.
175. Sauty, A.,, M. Dziejman,, R. A. Taha,, A. S. Iarossi,, K. Neote,, E. A. Garcia-Zepeda,, Q. Hamid,, and A. D. Luster. 1999. The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells. J. Immunol. 162:35493558.
176. Sawai, M. V.,, H. P. Jia,, L. Liu,, V. Aseyev,, J. M. Wiencek,, P. B. McCray, Jr.,, T. Ganz,, W. R. Kearney,, and B. F. Tack. 2001. The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment. Biochemistry 40:38103816.
177. Schnapp, D.,, and A. Harris. 1998. Antibacterial peptides in bronchoalveolar lavage fluid. Am. J. Respir. Cell Mol. Biol. 19:352356.
178. Schonwetter, B. S.,, E. D. Stolzenberg,, and M. A. Zasloff. 1995. Epithelial antibiotics induced at sites of inflammation. Science 267:16451648.
179. Schutte, B. C.,, J. P. Mitros,, J. A. Bartlettt,, J. D. Walters,, H. P. Jia,, M. J. Welsh,, T. L. Casavant,, and P. B. McCray. 2002. Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc. Nat. Acad. Sci. USA 99:21292133.
180. Scocchi, M.,, B. Skerlavaj,, D. Romeo,, and R. Gennaro. 1992. Proteolytic cleavage by neutrophil elastase converts inactive storage proforms to antibacterial bactenecins. Eur. J. Biochem. 209:589595.
181. Selsted, M. E.,, and S. S. Harwig. 1987. Purification, primary structure, and antimicrobial activities of a guinea pig neutrophil defensin. Infect. Immun. 55:22812286.
182. Selsted, M. E.,, D. Szklarek,, and R. I. Lehrer. 1984. Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect. Immun. 45:150154.
183. Selsted, M. E.,, Y. Q. Tang,, W. L. Morris,, P. A. McGuire,, M. J. Novotny,, W. Smith,, A. H. Henschen,, and J. S. Cullor. 1993. Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. J. Biol. Chem. 268:66416648.
184. Shai, Y. 1999. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alphahelical antimicrobial and cell non-selective membrane-lytic peptides. Biochim. Biophys. Acta 1462:5570.
185. Shi, J.,, and T. Ganz. 1998. The role of protegrins and other elastase-activated polypeptides in the bactericidal properties of porcine inflammatory fluids. Infect. Immun. 66:36113617.
186. Shi, J.,, G. Zhang,, H. Wu,, C. Ross,, F. Blecha,, and T. Ganz. 1999. Porcine epithelial beta-defensin 1 is expressed in the dorsal tongue at antimicrobial concentrations. Infect. Immun. 67:31213127.
187. Shugars, D. C.,, A. L. Alexander,, K. Fu,, and S. A. Freel. 1999. Endogenous salivary inhibitors of human immunodeficiency virus. Arch. Oral Biol. 44:445453.
188. Singh, P. K.,, H. P. Jia,, K. Wiles,, J. Hesselberth,, L. Liu,, B. D. Conway,, E. P. Greenberg,, E. V. Valore,, M. J. Welsh,, T. Ganz,, B. F. Tack,, and P. B. J. McCray. 1998. Production of β- defensins by human airway epithelia. Proc. Natl. Acad. Sci. USA 95:1496114966.
189. Singh, P. K.,, B. F. Tack,, P. B. McCray, Jr.,, and M. J. Welsh. 2000. Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am. J. Physiol. Ser. L 279:L799L805.
190. Sinha, S.,, N. Cheshenko,, R. I. Lehrer,, and B. C. Herold. 2003. NP-1, a rabbit alpha-defensin, prevents the entry and intercellular spread of herpes simplex virus type 2. Antimicrob. Agents Chemother. 47:494500.
191. Smith, J. J.,, S. M. Travis,, E. P. Greenberg,, and M. J. Welsh. 1996. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 85:229236.
192. Sohnle, P. G.,, M. J. Hunter,, B. Hahn,, and W. J. Chazin. 2000. Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14). J. Infect. Dis. 182:12721275.
193. Solomon, S.,, J. Hu,, Q. Zhu,, D. Belcourt,, H. P. Bennett,, A. Bateman,, and T. Antakly. 1991. Corticostatic peptides. J. Steroid Biochem. Mol. Biol. 40:391398.
194. Sorensen, O. E.,, J. B. Cowland,, K. Theilgaard-Monch,, L. Liu,, T. Ganz,, and N. Borregaard. 2003. Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J. Immunol. 170:55835589.
195. 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.
196. Steinbakk, M.,, C. F. Naess-Andresen,, E. Lingaas,, I. Dale,, P. Brandtzaeg,, and M. K. Fagerhol. 1990. Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet 336:763765.
197. Storici, P.,, and M. Zanetti. 1993. A cDNA derived from pig bone marrow cells predicts a sequence identical to the intestinal antibacterial peptide PR-39. Biochem. Biophys. Res. Commun. 196:10581065.
198. Storici, P.,, and M. Zanetti. 1993. A novel cDNA sequence encoding a pig leukocyte antimicrobial peptide with a cathelinlike pro-sequence. Biochem. Biophys. Res. Commun. 196:13631368.
199. Strukelj, B.,, J. Pungercar,, G. Kopitar,, M. Renko,, B. Lenarcic,, S. Berbic,, and V. Turk. 1995. Molecular cloning and identification of a novel porcine cathelin- like antibacterial peptide precursor. Biol. Chem. Hoppe-Seyler 376:507510.
200. Swart, P. J.,, E. M. Kuipers,, C. Smit,, B. W. Van Der Strate,, M. C. Harmsen,, and D. K. Meijer. 1998. Lactoferrin. Antiviral activity of lactoferrin. Adv. Exp. Med. Biol. 443:205213.
201. Tang, Y. Q.,, J. Yuan,, G. Osapay,, K. Osapay,, D. Tran,, C. J. Miller,, A. J. Ouellette,, and M. E. Selsted. 1999. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated α-defensins. Science 286:498502.
202. Territo, M. C.,, T. Ganz,, M. E. Selsted,, and R. Lehrer. 1989. Monocyte-chemotactic activity of defensins from human neutrophils. J. Clin. Investig. 84:20172020.
203. Tomee, J. F.,, G. H. Koeter,, P. S. Hiemstra,, and H. F. Kauffman. 1998. Secretory leukoprotease inhibitor: a native antimicrobial protein presenting a new therapeutic option? Thorax 53:114116.
204. Tominaga, T.,, J. Fukata,, Y. Naito,, Y. Nakai,, S. Funakoshi,, N. Fujii,, and H. Imura. 1990. Effects of corticostatin-I on rat adrenal cells in vitro. J. Endocrinol. 125:287292.
205. Torres, A. M.,, G. M. de Plater,, M. Doverskog,, L. C. Birinyi- Strachan,, G. M. Nicholson,, C. H. Gallagher,, and P. W. Kuchel. 2000. Defensin-like peptide-2 from platypus venom: member of a class of peptides with a distinct structural fold. Biochem. J. 348:649656.
206. Tossi, A.,, M. Scocchi,, M. Zanetti,, P. Storici,, and R. Gennaro. 1995. PMAP-37, a novel antibacterial peptide from pig myeloid cells. cDNA cloning, chemical synthesis and activity. Eur. J. Biochem. 228:941946.
207. Trabi, M.,, H. J. Schirra,, and D. J. Craik. 2001. Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes. Biochemistry 40:42114221.
208. Tran, D.,, P. A. Tran,, Y. Q. Tang,, J. Yuan,, T. Cole,, and M. E. Selsted. 2002. Homodimeric theta-defensins from Rhesus macaque leukocytes—isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J. Biol. Chem. 277:30793084.
209. Travis, S. M.,, B. A. Conway,, J. Zabner,, J. J. Smith,, N. N. Anderson,, P. K. Singh,, E. P. Greenberg,, and M. J. Welsh. 1999. Activity of abundant antimicrobials of the human airway. Am. J. Respir. Cell Mol. Biol. 20:872879.
210. Travis, S. M.,, P. K. Singh,, and M. J. Welsh. 2001. Antimicrobial peptides and proteins in the innate defense of the airway surface. Curr. Opin. Immunol. 13:8995.
211. Tsai, H.,, and L. A. Bobek. 1998. Human salivary histatins: promising anti-fungal therapeutic agents. Crit. Rev. Oral Biol. Med. 9:480497.
212. Turner, J.,, Y. Cho,, N. N. Dinh,, A. J. Waring,, and R. I. Lehrer. 1998. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob. Agents Chemother. 42:22062214.
213. Turpin, J. A.,, C. A. Schaeffer,, M. Bu,, L. Graham,, R. W. Buckheit, Jr.,, D. Clanton,, and W. G. Rice. 1996. Human immunodeficiency virus type-1 (HIV-1) replication is unaffected by human secretory leukocyte protease inhibitor. Antiviral Res. 29:269277.
214. Valore, E. V.,, and T. Ganz. 1992. Posttranslational processing of defensins in immature human myeloid cells. Blood 79:15381544.
215. Valore, E. V.,, E. Martin,, S. S. Harwig,, and T. Ganz. 1996. Intramolecular inhibition of human defensin HNP-1 by its propiece. J. Clin. Investig. 97:16241629.
216. Verkman, A. S.,, Y. Song,, and J. R. Thiagarajah. 2003. Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. Am. J. Physiol. Ser. C 284:C2C15.
217. Walker, C. M.,, D. J. Moody,, D. P. Stites,, and J. A. Levy. 1986. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 234:15631566.
218. Wang, W.,, A. M. Cole,, T. Hong,, A. J. Waring,, and R. I. Lehrer. 2003. Retrocyclin, an antiretroviral θ-defensin, is a lectin. J. Immunol. 170:47084716.
219. Wang, X.,, Z. Zhang,, J. P. Louboutin,, C. Moser,, D. J. Weiner,, and J. M. Wilson. 2003. Airway epithelia regulate expression of human beta-defensin 2 through Toll-like receptor 2. FASEB J. 17:17271729.
220. Wecke, J.,, M. Lahav,, I. Ginsburg,, and P. Giesbrecht. 1982. Cell wall degradation of Staphylococcus aureus by lysozyme. Arch. Microbiol. 131:116123.
221. Wehkamp, J.,, J. Harder,, M. Weichenthal,, O. Mueller,, K. R. Herrlinger,, K. Fellermann,, J. M. Schroeder,, and E. F. Stange. 2003. Inducible and constitutive beta-defensins are differentially expressed in Crohn’s disease and ulcerative colitis. Inflamm. Bowel Dis. 9:215223.
222. Weiss, J.,, M. Inada,, P. Elsbach,, and R. M. Crowl. 1994. Structural determinants of the action against Escherichia coli of a human inflammatory fluid phospholipase A2 in concert with polymorphonuclear leukocytes. J. Biol. Chem. 269: 2633126337.
223. Weiss, T. M.,, L. Yang,, L. Ding,, W. C. Wang,, A. J. Waring,, R. I. Lehrer,, and H. W. Huang. 2002. Two states of a cyclic antimicrobial peptide theta-defensin in lipid bilayers. Biophys. J. 82:7A.
224. Wilson, C. L.,, A. J. Ouellette,, D. P. Satchell,, T. Ayabe,, Y. S. Lopez-Boado,, J. L. Stratman,, S. J. Hultgren,, L. M. Matrisian,, and W. C. Parks. 1999. Regulation of intestinal alphadefensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113117.
225. Wright, G. W.,, C. E. Ooi,, J. Weiss,, and P. Elsbach. 1990. Purification of a cellular (granulocyte) and an extracellular (serum) phospholipase A2 that participate in the destruction of Escherichia coli in a rabbit inflammatory exudate. J. Biol. Chem. 265:66756681.
226. Yamaguchi, Y.,, T. Nagase,, R. Makita,, S. Fukuhara,, T. Tomita,, T. Tominaga,, H. Kurihara,, and Y. Ouchi. 2002. Identification of multiple novel epididymis-specific betadefensin isoforms in humans and mice. J. Immunol. 169:25162523.
227. Yang, D.,, Q. Chen,, O. Chertov,, and J. J. Oppenheim. 2000. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J. Leukoc. Biol. 68:914.
228. Yang, D.,, Q. Chen,, D. M. Hoover,, P. Staley,, K. D. Tucker,, J. Lubkowski,, and J. J. Oppenheim. 2003. Many chemokines including CCL20/MIP-3alpha display antimicrobial activity. J. Leukoc. Biol. 74:448455.
229. Yang, D.,, O. Chertov,, S. N. Bykovskaia,, Q. Chen,, M. J. Buffo,, J. Shogan,, M. Anderson,, J. M. Schroder,, J. M. Wang,, O. M. Howard,, and J. J. Oppenheim. 1999. β-Defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525528.
230. Zanetti, M.,, R. Gennaro,, and D. Romeo. 1995. Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett. 374:15.
231. Zanetti, M.,, L. Litteri,, R. Gennaro,, H. Horstmann,, and D. Romeo. 1990. Bactenecins, defense polypeptides of bovine neutrophils, are generated from precursor molecules stored in the large granules. J. Cell Biol. 111:13631371.
232. Zanetti, M.,, L. Litteri,, G. Griffiths,, R. Gennaro,, and D. Romeo. 1991. Stimulus-induced maturation of probactenecins, precursors of neutrophil antimicrobial polypeptides. J. Immunol. 146:42954300.
233. Zeya, H. I.,, and J. K. Spitznagel. 1966. Cationic proteins of polymorphonuclear leukocyte lysosomes. I. Resolution of antibacterial and enzymatic activities. J. Bacteriol. 91:750754.
234. Zeya, H. I.,, and J. K. Spitznagel. 1966. Cationic proteins of polymorphonuclear leukocyte lysosomes. II. Composition, properties and mechanism of antibacterial action. J. Bacteriol. 91:755762.
235. Zhang, L.,, W. Yu,, T. He,, J. Yu,, R. E. Caffrey,, E. A. Dalmasso,, S. Fu,, T. Pham,, J. Mei,, J. J. Ho,, W. Zhang,, P. Lopez,, and D. D. Ho. 2002. Contribution of human α-defensin-1, -2 and -3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 298:9951000.
236. Zhao, C.,, L. Liu,, and R. I. Lehrer. 1994. Identification of a new member of the protegrin family by cDNA cloning. FEBS Lett. 346:285288.
237. Zhao, C.,, T. Nguyen,, L. Liu,, R. E. Sacco,, K. A. Brogden,, and R. I. Lehrer. 2001. Gallinacin-3, an inducible epithelial β-defensin in the chicken. Infect. Immun. 69:26842691.
238. Zhu, Q.,, A. Bateman,, A. Singh,, and S. Solomon. 1989. Isolation and biological activity of corticostatic peptides (anti- ACTH). Endocr. Res. 15:129149.
239. Zhu, Q. Z.,, A. V. Singh,, A. Bateman,, F. Esch,, and S. Solomon. 1987. The corticostatic (anti-ACTH) and cytotoxic activity of peptides isolated from fetal, adult and tumor- bearing lung. J. Steroid Biochem. 27:10171022.
240. Zimmermann, G. R.,, P. Legault,, M. E. Selsted,, and A. Pardi. 1995. Solution structure of bovine neutrophil beta-defensin- 12: the peptide fold of the beta-defensins is identical to that of the classical defensins. Biochemistry 34:1366313671.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error