Antimicrobial peptides: An essential component of the skin defensive barrier

Current Topics in Microbiology and Immunology

Volumn 306, Issue , 2006, Pages 91-110

  Braff, M H ^a   Gallo, R L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENOMEDULLIN; ALPHA DEFENSIN; ALPHA INTERMEDIN; BETA DEFENSIN; BETA DEFENSIN 1; CATHELICIDIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; CATHELIN LIKE PRODOMAIN; CHEMOKINE; CHROMOGRANIN A; CHROMOGRANIN B; CXCL11 CHEMOKINE; CXCL9 CHEMOKINE; CYTOKINE; DEFENSIN; GAMMA INTERFERON INDUCIBLE PROTEIN 10; LYSOZYME; MYELOBLASTIN; NEUROPEPTIDE Y; POLYPEPTIDE ANTIBIOTIC AGENT; PROTEIN CRAMP; PSORIASIN; SECRETORY LEUKOCYTE PROTEINASE INHIBITOR; SUBSTANCE P; THETA DEFENSIN; UNCLASSIFIED DRUG; ANTIMICROBIAL CATIONIC PEPTIDE; CAP18 LIPOPOLYSACCHARIDE BINDING PROTEIN; CAP18 LIPOPOLYSACCHARIDE-BINDING PROTEIN; IMMUNOLOGIC FACTOR;

ACNE VULGARIS; ANGIOGENESIS; ANTIBIOTIC RESISTANCE; ANTIMICROBIAL ACTIVITY; ATOPIC DERMATITIS; BACTERIUM; CELL INFILTRATION; CYTOKINE PRODUCTION; EPITHELIUM CELL; FOLLICULITIS; FUNGUS; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HOST RESISTANCE; HUMAN; IMMUNOMODULATION; INNATE IMMUNITY; KERATINOCYTE; KLEBSIELLA PNEUMONIAE; LEUKOCYTE; MACROPHAGE; MAST CELL; NATURAL KILLER CELL; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN SYNTHESIS; PSORIASIS; REGULATORY MECHANISM; REVIEW; SEMINAL PLASMA; SKIN; SKIN CELL; SKIN CONDUCTANCE; SKIN INFECTION; STAPHYLOCOCCUS AUREUS; STRATUM CORNEUM; STREPTOCOCCUS AGALACTIAE; STREPTOCOCCUS GROUP A; SWEAT GLAND; VIRUS; WOUND HEALING; ANIMAL; BACTERIAL SKIN DISEASE; IMMUNOLOGY; PHYSIOLOGY;

BACTERIA (MICROORGANISMS); FUNGI;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; DEFENSINS; HUMANS; IMMUNITY, NATURAL; IMMUNOLOGIC FACTORS; KERATINOCYTES; SKIN; SKIN DISEASES, BACTERIAL;

EID: 33748094122     PISSN: 0070217X     EISSN: None     Source Type: Book Series    
DOI: 10.1007/3-540-29916-5_4     Document Type: Review

References (121)

1. Abachin E, Poyart C, Pellegrini E, Milohanic E, Fiedler F, Berche P, Trieu-Cuot P (2002) Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol Microbiol 43:1-14
2. Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jornvall H, Wigzell H, Gudmundsson GH (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96:3086-3093
3. Ashcroft GS, Lei K, Jin W, Longenecker G, Kulkarni AB, Greenwell-Wild T, Hale-Donze H, McGrady G, Song XY, Wahl SM (2000) Secretory leukocyte protease inhibitor mediatesnon-redundant functions necessary for normal wound healing. Nat Med 6:1147-1153
4. Bals R (2000) Epithelial antimicrobial peptides in host defense against infection. Respir Res 1:141-150
5. Bals R, Wilson JM (2003) Cathelicidins - a family of multifunctional antimicrobial peptides. Cell Mol Life Sci 60:711-720
6. Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM(1998) Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102:874-880
7. Bals R, Weiner DJ, Moscioni AD, Meegalla RL, Wilson JM (1999) Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect Immun 67:6084-6089
8. Befus AD, Mowat C, Gilchrist M, Hu J, Solomon S, Bateman A (1999) Neutrophil defensins induce histamine secretion from mast cells: mechanisms of action. J Immunol 163:947-953
9. Belaaouaj A, McCarthy R, Baumann M, Gao Z, Ley TJ, Abraham SN, Shapiro SD (1998) Mice lacking neutrophil elastase reveal impaired host defense against Gram-negative bacterial sepsis. Nat Med 4:615-618
10. Belas R, Manos J, Suvanasuthi R (2004) Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides. Infect Immun 72:5159-5167
11. Bick RJ, Poindexter BJ, Bhat S, Gulati S, Buja M, Milner SM (2004) Effects of cytokines and heat shock on defensin levels of cultured keratinocytes. Burns 30:329-333
12. Braff MH, Di Nardo A, Gallo RL (2005) Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies. J Invest Dermatol 124:394-400
13. Brogden KA, Ackermann M, McCray PB Jr, Tack BF (2003) Antimicrobial peptides in animals and their role in host defences. Int J Antimicrob Agents 22:465-478
14. Butmarc J, Yufit T, Carson P, Falanga V (2004) Human beta-defensin-2 expression is increased in chronic wounds. Wound Repair Regen 12:439-443
15. Carretero M, Del Rio M, Garcia M, Escamez MJ, Mirones I, Rivas L, Balague C, Jorcano JL, Larcher F (2004) A cutaneous gene therapy approach to treat infection through keratinocyte-targeted overexpression of antimicrobial peptides. FASEB J 18:1931-1933
16. Chaly YV, Paleolog EM, Kolesnikova TS, Tikhonov II, Petratchenko EV, Voitenok NN (2000) Neutrophil alpha-defensin human neutrophil peptidemodulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw 11:257-266
17. Christophers E, Henseler T (1987) Contrasting disease patterns in psoriasis and atopic dermatitis. Arch Dermatol Res 279 [Suppl]:S48-S51
18. Chronnell CM, Ghali LR, Ali RS, Quinn AG, Holland DB, Bull JJ, Cunliffe WJ, McKay IA, Philpott MP, Muller-Rover S (2001) Human beta defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions. J Invest Dermatol 117:1120-1125
19. Chung WO, Dale BA (2004) Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species. Infect Immun 72:352-358
20. Cole AM, Shi J, Ceccarelli A, Kim YH, Park A, Ganz T (2001) Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds. Blood 97:297-304
21. Collins LV, Kristian SA, Weidenmaier C, Faigle M, Van Kessel KP, Van Strijp JA, Gotz F, Neumeister B, Peschel A (2002) Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice. J Infect Dis 186:214-219
22. Conner K, Nern K, Rudisill J, O'Grady T, Gallo RL (2002) The antimicrobial peptide LL-37 is expressed by keratinocytes in condyloma acuminatum and verruca vulgaris. J Am Acad Dermatol 47:347-350
23. Darmstadt GL, Mentele L, Fleckman P, Rubens CE (1999) Role of keratinocyte injury in adherence of Streptococcus pyogenes. Infect Immun 67:6707-6709
24. De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069-1074
25. Di Nardo A, Vitiello A, Gallo RL (2003) Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol 170:2274-2278
26. Dinulos JG, Mentele L, Fredericks LP, Dale BA, Darmstadt GL (2003) Keratinocyte expression of human beta defensin 2 following bacterial infection: role in cutaneous host defense. Clin Diagn Lab Immunol 10:161-166
27. Donnarumma G, Paoletti I, Buommino E, Orlando M, Tufano MA, Baroni A (2004) Malassezia furfur induces the expression of beta-defensin-2 in human keratinocytes in a protein kinase C-dependent manner. Arch Dermatol Res 295:474-481
28. Dorschner RA, Lin KH, Murakami M, Gallo RL (2003) Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response. Pediatr Res 53:566-572
29. Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, Agerberth B, Gudmundsson GH, Gallo RL (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol 117:91-97
30. Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH (2002) Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106:517-525
31. Erdag G, Morgan JR (2002) Interleukin-1alpha and interleukin-6 enhance the antibacterial properties of cultured composite keratinocyte grafts. Ann Surg 235:113-124
32. Fang XM, Shu Q, Chen QX, Book M, Sahl HG, Hoeft A, Stuber F (2003) Differential expression of alpha- and beta-defensins in human peripheral blood. Eur J Clin Invest 33:82-87
33. Franzke CW, Baici A, Bartels J, Christophers E, Wiedow O (1996) Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation. J Biol Chem 271:21886-21890
34. Frick IM, Akesson P, Rasmussen M, Schmidtchen A, Bjorck L (2003) SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J Biol Chem 278:16561-16566
35. Frohm M, Agerberth B, Ahangari G, Stahle-Backdahl M, Liden S, Wigzell H, Gudmundsson GH (1997) The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 272:15258-15263
36. Gallo RL, Murakami M, Ohtake T, Zaiou M (2002) Biology and clinical relevance of naturally occurring antimicrobial peptides. J Allergy Clin Immunol 110:823-831
37. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76:1427-1435
38. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10:1033-1043
39. Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM (1997) Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88:553-560
40. Gudmundsson GH, Agerberth B (1999) Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system. J Immunol Methods 232:45-54
41. Gudmundsson GH, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R (1996) The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur J Biochem 238:325-332
42. Haake A, Scott GA, Holbrook KA (2003) Structure and function of the skin: overview of the epidermis and dermis. In: Freinkel RK, Woodley DT (eds) The biology of the skin. Parthenon, New York, pp 19-45
43. Harder J, Bartels J, Christophers E, Schroder JM (1997) A peptide antibiotic from human skin. Nature 387:861
44. Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707-5713
45. Harwig SS, Ganz T, Lehrer RI (1994) Neutrophil defensins: purification, characterization, and antimicrobial testing. Methods Enzymol 236:160-172
46. Hase K, Eckmann L, Leopard JD, Varki N, Kagnoff MF (2002) Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium. Infect Immun 70:953-963
47. Heilborn JD, Nilsson MF, Kratz G, Weber G, Sorensen O, Borregaard N, Stahle-Backdahl M (2003) The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 120:379-389
48. Henseler T, Christophers E (1995) Disease concomitance in psoriasis. J Am Acad Dermatol 32:982-986
49. Henzler Wildman KA, Lee DK, Ramamoorthy A (2003) Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. Biochemistry 42:6545-6558
50. Hornef MW, Wick MJ, Rhen M, Normark S (2002) Bacterial strategies for overcoming host innate and adaptive immune responses. Nat Immunol 3:1033-1040
51. Howell MD, Jones JF, Kisich KO, Streib JE, Gallo RL, Leung DY (2004) Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum. J Immunol 172:1763-1767
52. Islam D, Bandholtz L, Nilsson J, Wigzell H, Christensson B, Agerberth B, Gudmundsson G (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
53. Jones DE, Bevins CL (1993) Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett 315:187-192
54. Jung HH, Chae SW, Jung SK, Kim ST, Lee HM, Hwang SJ (2003) Expression of a cathelicidin antimicrobial peptide is augmented in cholesteatoma. Laryngoscope 113:432-435
55. Kamysz W, Okroj M (2003) Novel properties of antimicrobial peptides. Acta Biochim Pol 50:461-469
56. Kao CY, Chen Y, Zhao YH, Wu R (2003) ORFeome-based search of airway epithelial cell-specific novel human [beta]-defensin genes. Am J Respir Cell Mol Biol 29:71-80
57. Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, Issbrucker K, Unterberger P, Zaiou M, Lebherz C, Karl A, Raake P, Pfosser A, Boekstegers P, Welsch U, Hiemstra PS, Vogelmeier C, Gallo RL, Clauss M, Bals R (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665-1672
58. Kristian SA, Durr M, Van Strijp JA, Neumeister B, Peschel A (2003) MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads to protection against oxygen-independent neutrophil killing. Infect Immun 71:546-549
59. Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC (1995) Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 63:1291-1297
60. Lehrer RI, Ganz T (1999) Antimicrobial peptides in mammalian and insect host defence. Curr Opin Immunol 11:23-27
61. Lehrer RI, Ganz T (2002) Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 9:18-22
62. Lehrer RI, Daher K, Ganz T, Selsted ME (1985) Direct inactivation of viruses by MCP-1 and MCP-2, natural peptide antibiotics fromrabbit leukocytes. J Virol 54:467-472
63. Leung DY (2003) Infection in atopic dermatitis. Curr Opin Pediatr 15:399-404
64. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Invest 113:651-657
65. Liu AY, Destoumieux D, Wong AV, Park CH, Valore EV, Liu L, Ganz T (2002) Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 118:275-281
66. Liu L, Roberts AA, Ganz T (2003) By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide. J Immunol 170:575-580
67. Marchini G, Lindow S, Brismar H, Stabi B, Berggren V, Ulfgren AK, Lonne-Rahm S, Agerberth B, Gudmundsson GH (2002) The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol 147:1127-1134
68. McCray PB Jr, Bentley L (1997) Human airway epithelia express a beta-defensin. Am J Respir Cell Mol Biol 16:343-349
69. Midorikawa K, Ouhara K, Komatsuzawa H, Kawai T, Yamada S, Fujiwara T, Yamazaki K, Sayama K, Taubman MA, Kurihara H, Hashimoto K, Sugai M (2003) Staphylococcus aureus susceptibility to innate antimicrobial peptides, beta-defensins and CAP18, expressed by human keratinocytes. Infect Immun 71:3730-3739
70. Milner SM, Cole A, Ortega MR, Bakir MH, Gulati S, Bhat S, Ganz T (2003) Inducibility of HBD-2 in acute burns and chronic conditions of the lung. Burns 29:553-555
71. Morrison G, Kilanowski F, Davidson D, Dorin J (2002) Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect Immun 70:3053-3060
72. Moser C, Weiner DJ, Lysenko E, Bals R, Weiser JN, Wilson JM (2002) Beta-defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 70:3068-3072
73. Murakami M, Ohtake T, Dorschner RA, Schittek B, Garbe C, Gallo RL (2002) Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. J Invest Dermatol 119:1090-1095
74. Murakami M, Lopez-Garcia B, Braff M, Dorschner RA, Gallo RL (2004) Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol 172:3070-3077
75. Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, Tanaka S, Heumann D (2002) Augmentation of the lipopolysaccharide-neutralizing activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by replacement with hydrophobic and cationic amino acid residues. Clin Diagn Lab Immunol 9:972-982
76. Nickoloff BJ (1999) The immunologic and genetic basis of psoriasis. Arch Dermatol 135:1104-1110
77. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I (2002) A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106:20-26
78. Niyonsaba F, Hirata M, Ogawa H, Nagaoka I (2003) Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells. Curr Drug Targets Inflamm Allergy 2:224-231
79. Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL (2001) Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414:454-457
80. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 171:3262-3269
81. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 347:1151-1160
82. Oono T, Huh WK, Shirafuji Y, Akiyama H, Iwatsuki K (2003) Localization of human beta-defensin-2 and human neutrophil peptides in superficial folliculitis. Br J Dermatol 148:188-191
83. Oren A, Ganz T, Liu L, Meerloo T (2003) In human epidermis, beta-defensin 2 is packaged in lamellar bodies. Exp Mol Pathol 74:180-182
84. Ortega MR, Ganz T, Milner SM (2000) Human beta defensin is absent in burn blister fluid. Burns 26:724-726
85. Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Gotz F (1999) Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 274:8405-8410
86. Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, Kalbacher H, Nieuwenhuizen WF, Jung G, Tarkowski A, van Kessel KP, van Strijp JA (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
87. Philpott MP (2003) Defensins and acne. Mol Immunol 40:457-462
88. Poyart C, Pellegrini E, Marceau M, Baptista M, Jaubert F, Lamy MC, Trieu-Cuot P (2003) Attenuated virulence of Streptococcus agalactiae deficient in D-alanyllipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. Mol Microbiol 49:1615-1625
89. Putsep K, Carlsson G, Boman HG, Andersson M (2002) Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 360:1144-1149
90. Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC (1998) Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 152:1247-1258
91. Ramanathan B, Davis EG, Ross CR, Blecha F (2002) Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes Infect 4:361-372
92. Rieg S, Garbe C, Sauer B, Kalbacher H, Schittek B (2004) Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions. Br J Dermatol 151:534-539
93. Risso A (2000) Leukocyte antimicrobial peptides: multifunctional effector molecules of innate immunity. J Leukoc Biol 68:785-792
94. Rosenberger CM, Gallo RL, Finlay BB (2004) Interplay between antibacterial effectors: amacrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci U S A 101:2422-2427
95. Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL (2003) Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422:522-526
96. Schmidtchen A, Frick IM, Andersson E, Tapper H, Bjorck L (2002) Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 46:157-168
97. Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, Casavant TL, McCray PB Jr (2002) Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A 99:2129-2133
98. Scott MG, Gold MR, Hancock RE (1999) Interaction of cationic peptides with lipoteichoic acid and Gram-positive bacteria. Infect Immun 67:6445-6453
99. Selsted ME, Miller SI, Henschen AH, Ouellette AJ (1992) Enteric defensins: antibiotic peptide components of intestinal host defense. J Cell Biol 118:929-936
100. Seo SJ, Ahn SW, Hong CK, Ro BI (2001) Expressions of beta-defensins in human keratinocyte cell lines. J Dermatol Sci 27:183-191
101. Shi J, Ganz T (1998) The role of protegrins and other elastase-activated polypeptides in the bactericidal properties of porcine inflammatory fluids. Infect Immun 66:3611-3617
102. Singh PK, Tack BF, McCray PB Jr, Welsh MJ (2000) Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol 279:L799-L805
103. Sorensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N (2001) Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97:3951-3959
104. Sorensen O, Arnljots K, Cowland JB, Bainton DF, Borregaard N (1997) The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood 90:2796-2803
105. Sorensen OE, Cowland JB, Theilgaard-Monch K, Liu L, Ganz T, Borregaard N (2003) Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J Immunol 170:5583-5589
106. Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O'Neill S, McElvaney NG (2003) Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol 171:931-937
107. Travers JB, Norris DA, Leung DY (2001) The keratinocyte as a target for staphylococcal bacterial toxins. J Investig Dermatol Symp Proc 6:225-230
108. Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI (1998) Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 42:2206-2214
109. Uehara N, Yagihashi A, Kondoh K, Tsuji N, Fujita T, Hamada H, Watanabe N (2003) Human beta-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexpression. J Med Microbiol 52:41-45
110. Ulvatne H (2003) Antimicrobial peptides: potential use in skin infections. Am J Clin Dermatol 4:591-595
111. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T (1998) Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633-1642
112. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JH, Mader S, White JH (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173:2909-2912
113. Wiedow O, Harder J, Bartels J, Streit V, Christophers E (1998) Antileukoprotease in human skin: an antibiotic peptide constitutively produced by keratinocytes. Biochem Biophys Res Commun 248:904-909
114. Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC (1999) Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113-117
115. Yang D, Chen Q, Le Y, Wang JM, Oppenheim JJ (2001) Differential regulation of formyl peptide receptor-like 1 expression during the differentiation of monocytes to dendritic cells and macrophages. J Immunol 166:4092-4098
116. Zaiou M, Gallo RL (2002) Cathelicidins, essential gene-encoded mammalian antibiotics. J Mol Med 80:549-561
117. Zaiou M, Nizet V, Gallo RL (2003) Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence. J Invest Dermatol 120:810-816
118. Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 75:39-48
119. Zanetti M, Gennaro R, Scocchi M, Skerlavaj B (2000) Structure and biology of cathelicidins. Adv Exp Med Biol 479:203-218
120. Zasloff M (2002) Antimicrobial peptides in health and disease. N Engl J Med 347:1199-1200
121. Zhao C, Wang I, Lehrer RI (1996) Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 396:319-322