Defensin participation in innate and adaptive immunity

Current Pharmaceutical Design

Volumn 13, Issue 30, 2007, Pages 3131-3139

  Yang, De ^a   Liu, Zhen Hua ^b   Tewary, Poonam ^b   Chen, Qian ^b   de la Rosa, Gonzalo ^b   Oppenheim, Joost J ^b  

^a SAIC FREDERICK INC   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Activation; Adjuvant; Antimicrobial; Chemoattraction; Defensin; Dendritic cell; Immune response

Indexed keywords

ALPHA DEFENSIN; ALUMINUM POTASSIUM SULFATE; BETA DEFENSIN; CELL RECEPTOR; CYSTEINE; DEFENSIN; IMMUNOLOGICAL ADJUVANT; POLYPEPTIDE ANTIBIOTIC AGENT; THETA DEFENSIN; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; CELL MATURATION; CELLULAR IMMUNITY; DENDRITIC CELL; DRUG POTENCY; DRUG SYNTHESIS; EPITHELIUM CELL; HUMAN; IMMUNE RESPONSE; INFECTION; INNATE IMMUNITY; LEUKOCYTE; MALIGNANT NEOPLASTIC DISEASE; MAMMAL; MAST CELL; NONHUMAN; PHAGOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; T LYMPHOCYTE;

ANIMALS; DEFENSINS; HUMANS; IMMUNITY, ACTIVE; IMMUNITY, NATURAL; INFECTION; NEOPLASMS; STRUCTURE-ACTIVITY RELATIONSHIP; VIRUS DISEASES;

EID: 36248967729     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161207782110453     Document Type: Review

References (176)

1. Hoffmann JA, Kafatos FC, Janeway-Jr. CA, Ezekowitz RAB. Phylogenetic perspectives in innate immunity. Science 1999; 284: 1313-8.
2. Medzhitov R, Janeway-Jr. CA. Innate immunity: The virtues of a nonclonal system of recognition. Cell 1907; 91: 295-8.
3. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245-51.
4. Medzhitov R, Janeway Jr. CA. Innate immunity: Impact on the adaptive immune response. Curr Opin Immunol 1997; 9: 4-9.
5. Lehrer RI, Ganz T. Defensins of vertebrate animals. Curr Opin Immunol 2002; 14: 96-102.
6. Ganz T. Defensins: Antimicrobial peptides of innate immunity. Nat Rev Immunol 2003; 3: 710-20.
7. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002; 415: 389-95.
8. Boman HG. Antibacterial peptides: Basic facts and emerging concepts. J Intern Med 2003; 254: 197-215.
9. Schröder JM. Epithelial antimicrobial peptides: Innate local host response elements. Cell Mol Life Sci 1999; 56: 32-46.
10. Scott MG, Hancock REW. Cationic antimicrobial peptides and their multifunctional role in the immune system. Crit Rev Immunol 2002; 20: 407-31.
11. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 2004; 22: 181-315.
12. Selsted ME, Ouellette AJ. Mammalian defensins in die antimicrobial immune response. Nat Immunol 2005; 6: 551-7.
13. Yang D, Oppenheim JJ. Antimicrobial proteins act as "alarmins" in joint immune defense. Arthritis Rheum 2004; 50: 3401-3.
14. Oppenheim JJ, Yang D. Alarmins: Chemotactic activators of immune responses. Curr Opin Immunol 2005; 17: 359-65.
15. Selsted ME, Harwig SSL. Determination of the disulfide array in human defensin HNP-2. A covalently cyclized peptide. J Biol Chem 1989; 264: 4003-7.
16. Hill CP, Yee J, Selsted ME, Eisenberg D. Crystal structure of defensin HNP-3, an amphiphilic dimer: Mechanisms of membrane permeabilization. Science 1991; 251: 1481-5.
17. Tang Y-Q, Selsted ME. Characterization of the disulfide motif in BNBD-12, an antimicrobial b-defensin peptide fi-orn bovine neutrophils. J Biol Chem 1993; 48: 6649-53.
18. Zimmermann GR, Legault P, Selsted ME, Pardi A. Solution structure of bovine neutrophil b-defensin-12: The peptidefold of the b-defensins is identical to that of the classicial defensins. Biochemistry 1995; 34: 13663-71.
19. Tang Y-Q, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, et al. A cyclic antimicrobial peptide produced in primate leakocytes by the ligation of two truncated α-defensins. Science 1999; 286: 498-502.
20. Ganz T, Selsted ME, Szklarek D, Harwig SSL, Daher K, Bainton DF, et al. Defensins: Natural peptide antibiotics of human neutrophils. J Clin Invest 1985; 76: 1427-35.
21. Wilde CG, Grifft, JE, Marra MN, Suable JL, Scott RW. Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family. J Biol Chem 1989; 264: 11200-3.
22. Jones DE, Bevins, CL. Paneth cell of the human small intestine express an antimicrobial peptide gene. J Biol Chem 1992; 267: 23216-25.
23. Jones DE, Bevins CL. Defensin-6 mRNA in human Paneth cells: Implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett 1993; 315: 187-92.
24. Bertsch KW, Raida M, Magert H-J, Schulz-Knappe P, Forssmann W-G. hBD-1: a novel β-defensin from human plasma. FEBS Lett 1995; 368: 331-5
25. Harder J, Bartels J, Christophers E, Schröder JM. A peptide antibiotic from human skin. Nature 1997; 387: 861.
26. Harder J, Bartels J, Christophers E, Schröder JM. Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotics. J Biol Chem 2001; 276: 5707-13.
27. Garcia JR, Krause A, Schulz S, Rodrig-ez-Jimenez FJ, Kluver E, Adermann K, et al. Human β-defensin 4: A novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 2001; 15: 1819-21.
28. Jia HP, Schutte BC Schudy A, Linzmeier R, Guthmiller JM, Johnson GK, et al. Discovery of new human beta-defensins using a genomics-based approach. Gene 2001; 263: 211-8.
29. Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, et al. Discovery of five conserved beta -defensin gene clusters using a computational search strategy. Proc Natl Acad Sci USA 2002; 99: 2129-33.
30. Yamaguchi Y, Fukuhara S, Nagase T, Tomita T, Hitomi S, Kimura S, et al. A novel mouse β-defensin, mBD-6, predominantly expressed in skeletal muscle. J Biol Chem 2001; 276: 31510-4.
31. Motzkus D, Schulz-Maronde S, Heitland A, Schulz A, Forssmann WG, Jubner M, et al. The novel beta-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo. FASEB J 2006; 20: 1701-2.
32. Ouellette AJ, Lualdi JC. A novel mouse gene family coding for cationic, cysteine-rich peptides. Regulation in small intestine and cells of myeloid origin. J Biol Chem 1990; 265: 9831-7.
33. Ouellette AJ, Selsted ME. Paneth cell defensins: Endogenous peptide components of intestinal host defense. FASEB J 1996; 10: 1280-9.
34. Bals R, Goldman MJ, Wilson JM. Mouse β-defensin 1 is a salt-sensitive antimicrobial peptide present in epithelia of the lung and urogenital tract. Infect Immun 1998; 66: 1225-32.
35. Morrison GM, Davidson DJ, Dorin JR. A novel mouse beta defensin, Defb2, which is upregulated in the airways by lipopolysaccharide. FEBS Lett 1999; 442: 112-6.
36. Bals R, Wang X, Meegalla RL, Wattler S, Weiner DJ, Nehls MC, et al. Mouse β-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs. Infect Immun 1999; 67: 3542-7.
37. Conejo-Garcia JR, Benencia F, Courreges MC, Kang E, Mohamed-Hadley A, Buckanovich RJ, et al. Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat Med 2004; 10: 950-8.
38. Cole AM, Hong T, Boo LM, Nguyen T, Zhao C, Bristol G, et al. Retrocyclin: A primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci USA 2002; 99: 1813-8.
39. Sparkes RS, Kronenberg M, Heinzmann C, Daher KA, Klisak I, Ganz T, et al. Assignment of defensin gene(s) to human chromsoome 8p23. Genomics 1989; 5: 240-4.
40. Linzmeier R, Michaelson D, Liu L, Ganz T. The structure of neutrophil defensin genes. FEBS Lett 1993; 321: 267-73.
41. Palfree RG, Sadro LC, Solomon S. The gene encoding the human corticostatin HP-4 precursor contains a recent 86-base duplication and is located on chromosome 8. Mol Endocrinol 1993; 7: 199-205.
42. Bevins CL, Jones DE, Dutra A, Schaffzin J, Muenke M. Human enteric defensin genes: Chromosomal map position and a model for possible evolutionary relationships. Genomics 1996; 31: 95-106.
43. Liu L, Zhao C, Heng HHQ, Ganz T. The human β-defensin-1 and α-definsins are encoded by adjacent genes: Two peptide families with differing dipulfide topology share a common-ancestry. Genomics 1997; 43: 316-26.
44. Harder J, Siebert R, Zhang Y, Matthiesen P, Christophers E. Schlegelberger B, et al. Mapping of the gene encoding human 2b-Defensin-2 (DEFB2) to Chromosome Region 8p22-p23.1. Genomics 1997; 46: 472-5.
45. Linzmeier R, Ho CH, Hoang BV, Ganz T. A 450-kb contig of defensin genes-on human chromasome 8p23. Gene 1999; 233: 205-11.
46. Garcia JR, Jaumann F, Schulz S, Krause A, Rodriguez-Jimenez J, Forssmann U, et al. Identification of a novel, multifunctional β-defensin (human β-defensin 3) with specific antimicrobial activity: Its interaction with plasma membranes of Xenopw oocytes and the induction of macrophage chemoattraction. Cell Tissue Res 2001; 306: 257-64.
47. Yamaguchi Y, Nagase T, Mikita R, Fukuhara S, Tomita T, Tominaga T, et al. Identification of multiple novel epididymis-specific β-defensin isoforms in humans and mice. J Immunol 2002; 169: 2516-23.
48. Mars WM, Patmasiriwat P, Maity T, Huff V, Weil MM, Womack GF. Inheritance of unequal numbers of the genes that encoding the human neutrophil defensins HP-1 and HP-3. J Biol Chem 1995; 270: 30371-6.
49. Hughes AL. Evolutionary diversification of the mammalian defensins. Cell Mol Life Sci 1999; 56: 94-103.
50. Liu L, Wang L, Jia HP, Zhao C, Heng HHQ, Schutte BC, et al. Structure and mapping of the human β-defensin HBD-2 gene and its expression at sites of inflammation. Gene 1998; 222: 237-44.
51. Agerborth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, et al. The human antimicrobial and chemotactic peptides LL-37 and α-defensins are expressed by specific lymphocyte and monocyte populations. Blood 2000; 96: 3086-93.
52. Svinarich DM, Wolf NA, Gomez R, Gonik B, Romero R. Detection of human defensin 5 in reproductive tissues. Am J Obstet Gynecol 1997; 176.
53. Frye M, Bargon J, Dauletbaev N, Weber A, Wagner TOF, Gropp R Expression of human α-defensin 5 (HD5) mRNA in nasal and bronchial epithelial cells. J Clin Pathol 2000; 53: 770-3.
54. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray Jr. PB, Ganz T. Human β-defensin-1: An antimicrobial peptide of urogenital tissues. J Clin Invest 1998; 101: 1633-42.
55. Zhao C, Wang I, Lehrer RI. Widespread expression of β-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 1996; 396: 319-22.
56. Kaiser V, Diamond G. Expression of mammalian defensin genes. J Leukoc Biol 2000; 68: 779-84.
57. Selsted ME, Tang Y-Q, Morris WL, McGuire PA, Novotny MJ, Smith W, et al. Purification, primary structures, and antimicrobial activities of β-defensins, a new family of antimicrobial peptides from bovine neutrophils. J Biol Chem 1993; 268: 6641-8.
58. Huttner KM, Kozak CA, Bevins CL. The mouse genome encodes a single homolog of the antimicrobial peptide human β-defensin 1. FEBS Lett 1997; 413: 45-9.
59. Zhang G, Wu H, Shi J, Ganz T, Ross CR, Blecha F. Molecular cloning and tissue expression of porcine β-defensin-1. FEBS Lett 1998; 424: 37-40.
60. Diamond G, Russell JP, Bevins CL. Inducible expression of an antibiotic peptide gene in lipopolysaccharide-challenged tracheal epithelial cells. Proc Natl Acad Sci USA 1996; 93: 5156-60.
61. Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, et al. Production of β-defensins by human airway epithelia. Proc Natl Acad Sci USA 1998; 95:14961-6.
62. Schonwetter BS, Stolzenberg ED, Zasloff MA. Epithelial antibiotics induced at sites of inflammation. Science 1995; 276: 1645-8.
63. Fang X-M, Shu Q, Chen Q-X, Book M; Sahl H-G, Hoeft A, et al. Differential expression of α- and β-defensins in human peripheral blood. Eur J Clin Invest 2003; 33: 82-7.
64. Fehlbaum P, Rao M, Zasloff M, Anderson GM. An essential amino acid induces epithelial β-defensin expression. Proc Natl Acad Sci USA 2000; 97: 12723-8.
65. Sorensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T. Differential regulation of beta-defensin expression in human skin by microbial stimuli. J Immunol 2005; 174: 4870-9.
66. Ashitani J, Nakazato M, Mukae H, Taniguchi H, Date Y, Matsukura S. Recombinant granulocyte colony-stimulating factor induces production of human neutrophil peptides in lung cancer patients with neutropenia. Regul Pept 2000; 95: 87-92.
67. Froy O. Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathways. Cell Microbiol 2005; 7: 1387-97.
68. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005; 307: 731-4.
69. Voss E, Wehkamp J, Wehkamp K, Stange EF, Schroder JM, Harder J. NOD2/ CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J Biol Chem 2006; 281: 2005-11.
70. Boughan PK, Argent RH, Body-Malapel M, Park JH, Ewings KE, Bowie AG, et al. Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor: Critical regulators of beta-defensins during Helicobacter pylori infection. J Biol Chem 2006; 281: 11637-48.
71. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity 2004; 21: 241-54
72. Kao CY, Chen Y, Thai P, Wachi S, Huang F, Kim C, et al. IL-17 markedly up-regulates b-defensin-2 expression in human airway epithelium via JAK and NF-κB signaling pathways. J Immunol 2004; 173: 3482-91.
73. Sorensen OE, Thapa DR, Roupe KM, Valore EV, Sjobring U, Roberts AA, et al. Injury-induced innate immune response in human skin mediated by traimaivation of the epidermal growth factor receptor. J Clin Invest 2006; 116: 1878-85.
74. Valore EV, Ganz T. Posttranslational processing of defensins in immature human myeloid cells. Blood 1992; 79: 1538-44.
75. Harwig SS, Park AS, Lehrer RI. Characterizaton ot the defensin precursors in mature human neutrophils. Blood 1992; 79: 1532-7.
76. Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, et al. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 2002; 3: 583-90.
77. Wilson CL, Oueliette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, et al. Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999; 286: 113-7.
78. Wu Z, Li X, de Leeuw E, Ericksen B, Lu W. Why is the Arg5-Glu13 salt bridge conserved in mammalian alpha-defensins? J Biol Chem 2005; 280: 43039-47.
79. Semple C, Rolfe M, Dorin J. Duplication and selection in the evolution of primate β-defensin genes. Genome Biol 2003; 4: R31.
80. Pardi A, Zhang X-L, Selsted ME, Skalicky JJ, Yip PF. NMR studies of defensin antimicrobial peptides: 2. Tbree-dimensional structures of rabbit NP-2 and human HNP-1. Biochemistry 1992; 31: 11357-64.
81. Hoover DM, Chertov O, Lubkowski J. The structure of human β-defensin-1: New insight into structural properties of β-defensins. J Biol Chem 2001; 276: 39021-6.
82. Hoover DM, Rajashankar KR, Blumenthal R, Puri A, Oppenheim JJ, Chertov O, et al. The structure of human β-defensin-2 shows evidence of higher order oligomerization. J Biol Chem 2000; 275: 32911-8.
83. Zhang X-L, Selsted ME, Pardi A. NMR studies of defensin antimicrobial peptides: 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1. Biochemistry 1992; 31: 11348-56.
84. Bauer F, Schweimer K, Kluver E, Conejo-Garcia JR, Forssmann WG, Rosch P, et al. Structure determination of human and murine β-defensins reveals structural conservation in the absence of significant sequence similarity. Protein Sci 2001; 10: 2470-9.
85. McManus AM, Dawson NF, Wade JD, Carrington LE, Winzor DJ, Craik DJ. Three-dimentional structure of RK-1: A novel α-defensin peptide. Biochemistry 2000; 39: 15757-64.
86. Schibli DJ, Hunter HN, Aseyev V, Starner TD, Wiencek JM, McCray Jr. PB, et al. The solution structures of the human β-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus. J Biol Chem 2002; 277: 8279-89
87. Sawai MV, Jia HP, Liu L, Aseyev V, Wiencek JM, McCray Jr. PB, et al. The NMR structure of human β-defensin-2 reveals a novel a-helical segment. Biochemistry 2001; 40: 3810-6.
88. Szyk A, Wu Z, Tucker K, Yang D, Lu W, Lubkowski J. Crystal structures of human alpha-defensins HNP4, HD5, and HD6. Protein Sci 2006; 15: 2749-60.
89. Mandal M, Nagaraj R. Antibacterial activities and conformations of synthetic alpha-defensin HNP-1 and analogs with one, two and three disulfide bridges. J Pept Res 2002; 59: 95-104.
90. Maemoto A, Qu X, Rosengren KJ, Tanabe H, Henschen-Edman A, Craik DJ, et al. Functional analysis of the alpha-defensin disulfide array in mouse cryptdin-4. J Biol Chem 2004; 279: 44188-96.
91. Kluver E, Schulz-Maronde S, Scheid S, Meyer B, Forssmann WG, Adermann K. Structure-activity relation of human beta-defensin 3: Influence of disulfide bonds and cysteine substitution on antimicrobial activity and cytotoxicity. Biochemistry 2005; 44: 9804-16.
92. Wu Z, Hoover DM, Yang D, Boulegue C, Santamaria F, Oppenheim JJ, et al. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human β-defensin 3. Proc Natl Acad Sci USA 2003; 100: 8880-5.
93. Pazgier M, Prahl A, Hoover M, Lubkowski J. Studies of the Biological Properties of Human beta-Defensin 1. J Biol Chem 2007; 282: 1819-29
94. Selsted ME, Szklarek D, Lehrer RI. Purification and antibacterial activities of antimicrobial peptides of rabbit granulocytes. Infect Immun 1984; 45: 150-4.
95. Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM. Human β-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 1997; 88: 553-60.
96. Lehrer RI, Barton A, Daher KA, Harwig SS, Ganz T, Selsted ME. Interaction of human defensius with Escherichia coli: Mechanism of bactericidal activity. J Clin Invest 1989; 84: 553-61.
97. Lohner K, Latal A, Lehrer RI, Ganz T. Differential scanning microcalorimetry indicates that human defensin, HNP-2, interacts specifically with biomembrane mimetic systems. Biochemistry 1997; 36: 1525-31.
98. Kagan BL, Selsted ME, Ganz T, Lehrer RI. Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc Natl Acad Sci USA 1990; 87: 210-4.
99. Wimley WC, Selsted ME, White SH. Interactions between human defensins and lipid bilayers: Evidence for formation of multimeric pores. Protein Sci 1994; 3: 1362-73.
100. Yenugu S, Hamil KG, Birse CE, Ruben SM, French FS, Hall SH. Antibacterial properties of the sperm-binding proteins and peptides of human epididymis 2 (HE2) family; salt sensitivity, structural dependence and their interaction with outer and cytoplasmic membranes of Escherichia coli. Biochem J 2003; 372: 473-83.
101. Yenugu S, Hamil KG, Radhakrishnan Y, French FS, Hall SH. The androgen-regulated epididymal sperm-binding protein, human β-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial β-defensin. Endocrinology 2004; 145: 3165-73.
102. Bals R, Wang X, Wu Z. Bafna V, Zasloff M, Wilson JM. Human β-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 1998; 102: 874-80.
103. Porter EM, van Dam E, Valore EV, Ganz T. Broad-spectrum antimicrobial activity of human intestinal defensin 5. Infect Immun 1997; 65: 2396-401.
104. Pörto GA, Lee JH, de Azavedo J, Crandall I, Whitehead T, Tullis E, et al. Direct and indirect bacterial killing functions of neutrophil defensins in lung explana. Am J Physiol 2001; 281: L1240-L7.
105. Huang GT, Zhang HB, Kim D, Liu L, Ganz T. A model for antimicrobial gene therapy: Demonstration of human β-defensin 2 antimicrobial activities in vivo. Hum Gene Ther 2002; 20: 2017-25.
106. Lehrer RI, Daher K, Ganz T, Selsted ME. Direct inactivation of viruses by MCP-1 and MCP-2, natural peptide antibiotics from rabbit leukocytes. J Virol 1985; 54: 467-72.
107. Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, et al. Contribution of human α-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 2002; 298: 995-1000.
108. Nakashima H, Yamamoto N, Masuda M, Fujii N. Defensins inhibit HIV replication in vitro. AIDS 1993; 7: 1129.
109. Quinones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, et al. Human epithelial β-defensin 2 and 3 inhibit HIV-1 replication. AIDS 2003; 17: F39-48.
110. Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P, La Terra Maggiore GM, et al. Human beta-defensins supppress human immunodeficiency virus infection: Potential role in mucosal protection. J Virol 2005; 79: 14318-29.
111. Wang W, Cole AM, Hong T, Waring AJ, Lehrer RI. Retrocyclin, an antiretroviral χ-defensin, is a lectin. J Immunol 2003; 170: 4708-16.
112. Bastian A, Schafer H. Human α-defensin 1 (HNP-1) inhibits adenoviral infection in vitro. Regul Pept 2001; 101: 157-61.
113. Sinha S, Cheshenko N, Lehrer RI, Herold BC. NP-1, a rabbit alphadefensin, prevents the entry and intercellular spread of herpes simplex virus type 2. Antimicrob Agents Chemother 2003; 47: 494-500
114. Yasin B, Wang W, Pang M, Cheshenko N, Hong T, Waring AJ, et al. Theta defensins protect cells from infection by herpes simplex virus by inhibiting viral adhesion and entry. J Virol 2004; 78: 5147-56.
115. Leikina E, Delanoe-Ayari H, Melikov K, Cho MS, Chen A, Waring AJ, et al. Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins. Nat Immunol 2005; 6:995-1001.
116. ChangTL, Vargas J Jr, DelPortillo A, Klotman ME. Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 2005; 115: 765-73.
117. Wang W, Owen SM, Rudolph DL, Cole AM, Hong T, Waring AJ, et al. Activity of alpha- and theta-defensins against primary isolates of HIV-1. J Immunol 2004; 173: 515-20.
118. Gallo SA, Wang W, Rawat SS, Jung G, Waring AJ, Cole AM, et al. Theta-defensins prevent HIV- 1 Env-mediated fusion by binding gp41 and blocking 6-helix bundle formation. J Biol Chem 2006; 281: 19787-92.
119. Kim C, Gajendran N, Mittrucker HW, Weiwad M, Song YH, Hurwitz R, et al. Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc Natl Acad Sci USA 2005; 102:4830-5.
120. Wang W, Mulakala C, Ward SC, Jung G, Luong H, Pham D, et al. Retrocyclins kill bacilli and germinating spores of Bacillus anthracis and inactivate anthrax lethal toxin. J Biol Chem 2006; 281: 32755-64
121. Kim C, Slavinskaya Z, Merrill AR, Kaufmann SH. Human alpha-defensins neutralize toxins of the mono-ADP-ribosyltransferase family. Biochem J 2006; 399: 225-9.
122. Scott MG, Vreugdenhil AC, Buurman WA, Hancock REW. Cutting edge: cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein. J Immunol 2000; 164:549-53.
123. Shu Q, Shi Z, Zhao Z, Chen Z, Yao H, Chen Q, et al. Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of beta-defensin-2 in rats. Shock 2006; 26: 365-71
124. Territo MC, Gan T, Selsted ME, Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest:1989; 84: 2017-20
125. Yang D, Biragyn A, Kwak LW, Oppenheim JJ. Mammalian defensins in immunity: More than just microbicidal. Trends Inummol 2002; 23: 291-6
126. Verbanac D, Manetti M, Romeo D. Chemotactic and protease-inhibiting activities of antibiotic peptide precursors. FEBS Lett 1993; 371: 255-8.
127. Niyonsaba F, Ogawa H, Nagaoka I. Human P-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology 2004; 111: 273-81.
128. Liu YJ. Dendritic cell-subsets and lineages, and their functions in innate and adaptive immunity. Cell 2001; 106: 259-62.
129. Yang D, Chen Q, Chertov O, Oppenheim JJ. Human neutrophil defensins selectively chemoattract naïve T and immature dendritic cells. J Leukoc Biol 2000; 68: 9-14.
130. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, et al. b-Defensins: Linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525-8.
131. Biragyn A, Surenhu M, Yang D, Ruffini PA, Haines BA, Klyushnenkova E, et al. Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens. J Immunol 2001; 167: 6644-53.
132. 2 production from mast cells. Eur J Immunol 2001; 31: 1066-75.
133. Niyonsaba F, lwabuchi K, Matsuda H, Ogawa H, Nagaoka I. Epithelia cell-derived human β-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxmi-sensitive and phospholipase C-dependent pathway. Int Immunol 2002; 14: 421-6.
134. Yamashita T, Saito K. Purification, primary structure, and biological activity of guinea pig neutrophil cationic peptides. Infect Immun 1989; 57: 2405-9.
135. Befus AD, Mowat C, Gilchrist M, Hu J, Solomon S, Bateman A. Neutrophil defensins induce histamine secretion from mast cells: Mechanisms of action. J Inummol 1999; 163: 947-53.
136. van Wetering S, Mannesse-Lazeroms SPG, van Sterkenburg MAJA, Daha MR, Dijkman JH, Hiemstra PS. Effect of defensins on interleukin-8 synthesis in airway epithelial cells. Am J Physiol 1997; 272: L888-L96.
137. van Wetering S, Mannesse-Lazeroms SPG, Dijkman JH, Hiermstra PS. Effect of neutrophil serine proteinases did defensins on lung epithelial cells: modulation of cytotoxicity and EL-8 production. J Leukoc Biol 1997; 62: 217-26.
138. van Wetering S, Mannesse-Lazeroms SP, van Sterkenburg MA, Hiernstra PS. Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: Modulation by dexamediasene. Inflamn Res 2002; 54: 8-15.
139. Zhang H, Porro G, Orzech N, Mullen B, Liu M, Slutsky AS. Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose:rElated fashion. Am J Physiol 2001; 280: L947-54.
140. Niyonsaba F, Ushio H, Nagaoka I, Okumura K, Ogawa H. The human beta-defensins (1, -2, -3, -4) and cathelicidin LL-37 induce IL- 18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J Immunol 2005; 175: 1776-84.
141. Sampanthanarak P, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, et al. The effect of antibacterial peptide human betadefensin-2 on interleukin- 18 secretion by keratinocytes. J Dermatol Sci 2005; 37: 188-91.
142. Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, et al. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 2007; 127: 594-604.
143. Echtenacher B, Mannel DN, Hultner L. Criticalprotective role of mast cells in a model of acute septic peritonitis. Nature 1996; 381: 75-7.
144. Rviya R, Ikeda T, Ross E, Abraham SN. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNFa. Nature 1996; 381: 77-80.
145. Baggiolini M. Chemokines and leukocyte traffic. Nature 1998; 392: 565-8.
146. Zlotnik A, Yoshie 0. Chemokines: A new classification system and their role in immunity. Immunity 2000; 12: 121-7.
147. Yang D, Chertov O, Oppenheim JJ. Partipation of mammalian defensins and cathelicidins in antimicrobial immunity: Receptors and activities of human defensins and cathelicidin (LL37). J Leukoc Biol 200 1; 69: 691-7.
148. Yang D, Howard OMZ, Chen Q, Oppenheim JJ. Cutting Edge: ITnm tu dendritic cells generated from monocytes in the presence of TGF-β express. functional C-C chemokine receptor 6. J Immunol 1999; 163: 1737-41.
149. Yomogida S, Nagaoka I. Saito K, Yamashita E. Evanuation of the effects of defensins, on neutrophil functions. Inflamm Res 1996; 4:5: 62-7.
150. Patarroyo M. Adhesion molecules mediating recruitment of monocytes to inflamed tissue. Immunobiology 1994; 191: 474-7.
151. Hayflick JS, Kilgannon P, Gallatin WM. The intercellular adhesion molecule (ICAM) family of proteins: New members and novel functions. Immunol Res 1998; 17: 313-27.
152. Ichinose M, Asai M, Imai K, Sawada M. Enhancement of phagocytosis by corticostatin I (CSI) in cultured mouse peritoneal macrophages. Immunopharmacol 1996; 35: 103-9.
153. Palucka K, Banchereau J. How dendritic cells and microbes interact to elicit or subvert protective immune responses. Curr Opin Immunol 2002; 14: 420-31.
154. Biragyn A, Ruffini PA, Coscia M, Harvey LK, Neelapu SS, Baskar S, et al. Chemokine receptor-mediated delivery directs self-tumor antigen efficiently into the class II processing pathway in vitro and induces protective immunity in vivo. Blood 2004; 104: 1961-9
155. Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, et al. Toll-like receptor 4-dependent activation of dendritic cells by β-defensin 2. Science 2002; 298: 1025-9.
156. Yang D, Rosenberg HF, Chen Q, Dyer KD, Kurosaka K, Oppenheim JJ. Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells. Blood 2003; 102: 3396-403
157. Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 2004; 5: 825-30.
158. Messmer D, Yang H, Telusma G, Knoll F, Li J, Messmer B, et al. High mobility group box protein 1: An endogenous signal for dendritic cell maturation and Th1 polarization. J Immunol 2004; 173: 307-13.
159. Yang D, Chen Q, Yang H, Tracey KJ, Bustin M, Oppenheim JJ. High mobility group box-1 (HMGB1) protein induces the migration and activation of human dendritic cells and acts as an alarmin. J Leukoc Biol 2007; 81: 59-66.
160. Yang D, Chen Q, Rosenberg HF, Rybak SM, Newton DL, Wang ZY, et al. Human ribonuclease A superfamily members, eosinophil-derived neurotoxin and pancreatic ribonuclease, induce dendritic cell maturation∠d activation. J Immunol 2004; 173: 6134-42.
161. Kurosaka K, Chen Q, Yarovinsky F, Oppenheim JJ, Yang D. Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant. J Immunol 2005; 174: 6257-65.
162. Lillard Jr. JW, Boyaka PN, Chertov O, Oppenheim JJ, McGhee JR. Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc Natl Acad Sci USA 1999; 96: 651-6.
163. Brogden KA, Heidari M, Sacco RE, Palmquist D, Guthmiller JM, Johnson GK, et al. Defensin-induced adaptive immunity in mice and its potential in preventing periodontal disease. Oral Microbiol Immunol 2003; 18: 95-9.
164. Tani K, Murphy WJ, Chertov O, Salcedo I, Koh CY, Utsunomiya I, et al. Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens. Int Immunol 2000; 12: 691-700.
165. Biragyn A, Belyakov IM, Chow Y-H, Dimitrov Berzofsky JA, Kwak LW. DNA vaccines encoding human immunodeficiency virus-1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses. Blood 2002; 100: 1153-9.
166. Ma XT, Yu-B, An LL, Dong CY, Lin YM, Shi Y, et al. Vaccine with beta-defensin 2-transduced leukemic cells activates innate and adaptive immunity to elicit potent antileukemia responses. Cancer Res 2006; 66: 1169-76.
167. Mosmann TR, Coffman RL. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7:145-73.
168. Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, et al. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoatttactant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 1996; 271: 2935-40.
169. Moser C, Weiner DJ, Eysenko E, Bals R, Weiser JN, Wilson JM. β-Defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 2002; 70:3068-72.
170. Morrison G, Kilanowski F, Davidson D, Dorin J. Characterization of the mouse β defensin 1, Defb1, mutant mouse model. Infect Immun 2002; 70: 3053-60.
171. Salzman NH, Ghosh D. Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003; 422: 522-6.
172. Welling MM, Hiemstra PS, van-den-Barselaar MT, Paulusma-Annema A, Nibbering PH, Pauwel EKJ, et al. Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation. J Clin Invest 1998; 102: 1583-90
173. Elahi S, Buchanan RM, Attah-Poku S, Townsend HG, Babiuk LA, Gerdts V. The-host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets. Infect Immun 2006; 74: 2338-52.
174. Amati L, Pepe W, Passeri ME, Mastronardi ML, Jirillo E, Covelli V. Toll-like receptor signaling mechanisms involved in dendrific cell activation: Potential therapeutic control of T cell polarization. Curr Pharin Des 2006; 12(32): 4247-54.
175. Frantz S, Bauersachs J, Kelly RA. UTate immunity and the heart. Curr Pharm Des 2005; 11(10): 1279-90.
176. Garzino-Demo A. Chemokines and defensins as HIV suppressive factors: An evolving story. Curr Pharm, Des 2007; 13(2): 163-72.