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

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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
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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: 3086 3093.
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: 195 199.
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: 849 854.
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: 860 863.
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: 5760 5766.
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: 2628 2632.
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: 5397 5403.
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: 141 149.
9. Andreu, D.,, and L. Rivas. 1998. Animal antimicrobial peptides: an overview. Biopolymers 47: 415 433.
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: 792 799.
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: 575 583.
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: 113 118.
13. Bals, R. 2000. Epithelial antimicrobial peptides in host defense against infection. Respir. Res. 1: 141 150.
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: 9541 9546.
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: 21 25.
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: 10654 10659.
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: 29731 29736.
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: 472 479.
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: 331 335.
20. Billiau, A., and K. Vandenbroeck,. 2000. IFN-γ, p. 641 688. 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: 937 943.
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: 1025 1029.
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: 6644 6653.
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: 3131 3137.
25. Boman, H. G. 1995. Peptide antibiotics and their role in innate immunity. Annu. Rev. Immunol. 13: 61 92.
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: 201 206.
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: 5948 5954.
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: 4256 4259.
29. Bullen, J. J.,, and J. A. Armstrong. 1979. The role of lactoferrin in the bactericidal function of polymorphonuclear leucocytes. Immunology 36: 781 791.
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: 3902 3907.
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: 6777 6784.
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: 215 220.
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: 3751 3758.
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: 2935 2940.
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: 3267 3275.
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: 623 627.
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: 1813 1818.
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: 5 10.
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: 6985 6991.
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: 297 304.
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: 173 176.
44. Daher, K. A.,, M. E. Selsted,, and R. I. Lehrer. 1986. Direct inactivation of viruses by human granulocyte defensins. J. Virol. 60: 1068 1074.
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: 3952 3956.
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: 91 97.
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: 59 64.
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: 517 525.
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: 1321 1331.
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: 16 21.
51. Ellison, R. T., III,, and T. J. Giehl. 1991. Killing of Gramnegative bacteria by lactoferrin and lysozyme. J. Clin. Investig. 88: 1080 1091.
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: 417 429.
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: 1327 1334.
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: 543 550.
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: 627 634.
56. Fleming, A. 1922. On a remarkable bacteriolytic element found in tissues and secretions. Proc. R. Soc. Lond. Ser. B 93: 306 317.
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: 221 225.
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: 13088 13093.
59. Ganz, T. 1999. Defensins and host defense. Science 286: 420 421.
60. Ganz, T. 2001. Defensins in the urinary tract and other tissues. J. Infect. Dis. 183( Suppl. 1): S41 S42.
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: 2388 2392.
62. Ganz, T.,, and R. I. Lehrer. 1994. Defensins. Curr. Opin. Immunol. 6: 584 589.
63. Ganz, T.,, and R. I. Lehrer. 1997. Antimicrobial peptides of leukocytes. Curr. Opin. Hematol. 4: 53 58.
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: 552 556.
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: 1427 1435.
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: 257 264.
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: 860 870.
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: 583 590.
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: 553 560.
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: 2561 2567.
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: 382 386.
72. Groisman, E. A. 2001. The pleiotropic two-component regulatory system PhoP-PhoQ. J. Bacteriol. 183: 1835 1842.
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: 1767 1772.
74. Gudmundsson, G. H.,, and B. Agerberth. 1999. Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system. J. Immunol. Methods 232: 45 54.
75. Hancock, R. E. 1997. Peptide antibiotics. Lancet 349: 418 422.
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: 79 83.
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: 5707 5713.
78. Harder, J.,, J. Bartels,, E. Christophers,, and J.-M. Schroeder. 1997. A peptide antibiotic from human skin. Nature 387: 861 862.
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: 380 388.
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: 65 69.
81. Harwig, S. S.,, A. S. Park,, and R. I. Lehrer. 1992. Characterization of defensin precursors in mature human neutrophils. Blood 79: 1532 1537.
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: 73 85.
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: 137 144.
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: 6820 6826.
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: 4520 4524.
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: 9472 9477.
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: 17650 17655.
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: 1481 1485.
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: 943 947.
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: 2564 2576.
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: 37647 37654.
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: 39021 39026.
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: 32911 32918.
95. Hughes, A. L. 1999. Evolutionary diversification of the mammalian defensins. Cell Mol. Life Sci. 56: 94 103.
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: 27 32.
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: 180 185.
98. Janeway, C. A., Jr.,, and R. Medzhitov. 2002. Innate immune recognition. Annu. Rev. Immunol. 20: 197 216.
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: 3718 3724.
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: 2771 2782.
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: 23216 23225.
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: 187 192.
103. Kalfa, V. C.,, and K. A. Brogden. 1999. Anionic antimicrobial peptide-lysozyme interactions in innate pulmonary immunity. Int. J. Antimicrob. Agents 13: 47 51.
104. Kaliner, M. A. 1991. Human nasal respiratory secretions and host defense. Am. Rev. Respir. Dis. 144: S52 S56.
105. Kaliner, M. A. 1992. Human nasal host defense and sinusitis. J. Allergy Clin. Immunol. 90: 424 430.
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: 2588 2595.
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: 231 236.
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: 95 115.
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: 720 728.
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: 1291 1297.
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: 3888 3893.
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: 445 456.
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: 2678 2681.
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: 553 561.
115. Lehrer, R. I.,, C. L. Bevins,, and T. Ganz,. 1999. Defensins and other antimicrobial peptides, p. 89 99. 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: 467 472.
117. Lehrer, R. I.,, and T. Ganz. 2002. Defensins of vertebrate animals. Curr. Opin. Immunol. 14: 96 102.
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: 1829 1835.
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: 207 211.
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: 461 464.
121. Levy, J. A. 2001. The importance of the innate immune system in controlling HIV infection and disease. Trends Immunol. 22: 312 316.
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: 1327 1333.
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: 651 656.
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: 316 320.
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: 514 519.
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: 13723 13728.
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: F23 F32.
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: 552 556.
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: 93 98.
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: 1034 1043.
131. Martin, E.,, T. Ganz,, and R. I. Lehrer. 1995. Defensins and other endogenous peptide antibiotics of vertebrates. J. Leukoc. Biol. 58: 128 136.
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: 2740 2745.
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: 1005 1015.
134. Matsuzaki, K. 2001. Why and how are peptide-lipid interactions utilized for self defence? Biochem. Soc. Trans. 29: 598 601.
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: 413 421.
136. McCray, P. B.,, and L. Bentley. 1997. Human airway epithelia express a β-defensin. Am. J. Respir. Cell Mol. Biol. 16: 343 349.
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: 920 930.
138. Milner, S. M.,, and M. R. Ortega. 1999. Reduced antimicrobial peptide expression in human burn wounds. Burns 25: 411 413.
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: 3934 3940.
140. Monell, C. R.,, and M. Strand. 1994. Structural and functional similarities between synthetic HIV gp41 peptides and defensins. Clin. Immunol. Immunopathol. 71: 315 324.
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: 112 116.
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: 875 881.
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: 408 413.
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: 417 421.
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: 1647 1654.
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: 421 426.
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: 1066 1075.
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: 454 457.
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: 4720 4725.
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: 6718 6724.
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: 7472 7477.
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: 180 182.
153. Ortega, M. R.,, T. Ganz,, and S. M. Milner. 2000. Human beta defensin is absent in burn blister fluid. Burns 26: 724 726.
154. Ouellette, A. J.,, and C. L. Bevins. 2001. Paneth cell defensins and innate immunity of the small bowel. Inflamm. Bowel Dis. 7: 43 50.
155. Ouellette, A. J.,, and M. E. Selsted. 1996. Paneth cell defensins: endogenous peptide components of intestinal host defense. FASEB J. 10: 1280 1289.
156. Panyutich, A.,, and T. Ganz. 1991. Activated alpha 2-macroglobulin is a principal defensin-binding protein. Am. J. Respir. Cell Mol. Biol. 5: 101 106.
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: 978 985.
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: 351 357.
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: 169 173.
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: 28372 28379.
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: 1067 1076.
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: 8405 8410.
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: 1643 1650.
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: 1055 1062.
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: 5161 5165.
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: F39 F48.
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: 914 919.
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: 1528 1535.
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: 262 270.
170. Rothenberg, R. B.,, M. Scarlett,, C. del Rio,, D. Reznik,, and C. O’Daniels. 1998. Oral transmission of HIV. AIDS 12: 2095 2105.
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: 522 526.
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: 875 883.
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: 87 93.
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: 213 220.
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: 3549 3558.
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: 3810 3816.
177. Schnapp, D.,, and A. Harris. 1998. Antibacterial peptides in bronchoalveolar lavage fluid. Am. J. Respir. Cell Mol. Biol. 19: 352 356.
178. Schonwetter, B. S.,, E. D. Stolzenberg,, and M. A. Zasloff. 1995. Epithelial antibiotics induced at sites of inflammation. Science 267: 1645 1648.
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: 2129 2133.
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: 589 595.
181. Selsted, M. E.,, and S. S. Harwig. 1987. Purification, primary structure, and antimicrobial activities of a guinea pig neutrophil defensin. Infect. Immun. 55: 2281 2286.
182. Selsted, M. E.,, D. Szklarek,, and R. I. Lehrer. 1984. Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect. Immun. 45: 150 154.
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: 6641 6648.
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: 55 70.
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: 3611 3617.
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: 3121 3127.
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: 445 453.
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: 14961 14966.
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: L799 L805.
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: 494 500.
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: 229 236.
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: 1272 1275.
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: 391 398.
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: 5583 5589.
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: 3951 3959.
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: 763 765.
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: 1058 1065.
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: 1363 1368.
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: 507 510.
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: 205 213.
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: 498 502.
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: 2017 2020.
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: 114 116.
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: 287 292.
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: 649 656.
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: 941 946.
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: 4211 4221.
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: 3079 3084.
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: 872 879.
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: 89 95.
211. Tsai, H.,, and L. A. Bobek. 1998. Human salivary histatins: promising anti-fungal therapeutic agents. Crit. Rev. Oral Biol. Med. 9: 480 497.
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: 2206 2214.
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: 269 277.
214. Valore, E. V.,, and T. Ganz. 1992. Posttranslational processing of defensins in immature human myeloid cells. Blood 79: 1538 1544.
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: 1624 1629.
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: C2 C15.
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: 1563 1566.
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: 4708 4716.
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: 1727 1729.
220. Wecke, J.,, M. Lahav,, I. Ginsburg,, and P. Giesbrecht. 1982. Cell wall degradation of Staphylococcus aureus by lysozyme. Arch. Microbiol. 131: 116 123.
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: 215 223.
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: 26331 26337.
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: 113 117.
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: 6675 6681.
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: 2516 2523.
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: 9 14.
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: 448 455.
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: 525 528.
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: 1 5.
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: 1363 1371.
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: 4295 4300.
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: 750 754.
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: 755 762.
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: 995 1000.
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: 285 288.
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: 2684 2691.
238. Zhu, Q.,, A. Bateman,, A. Singh,, and S. Solomon. 1989. Isolation and biological activity of corticostatic peptides (anti- ACTH). Endocr. Res. 15: 129 149.
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: 1017 1022.
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: 13663 13671.

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