Biological roles of host defense peptides: Lessons from transgenic animals and bioengineered tissues

Cell and Tissue Research

Volumn 343, Issue 1, 2011, Pages 213-225

  Dybvig, Tova ^a   Facci, Marina ^a   Gerdts, Volker ^a,b   Wilson, Heather L ^a  

^a UNIVERSITY OF SASKATCHEWAN   (Canada)

^b UNIVERSITY OF SASKATCHEWAN   (Canada)

Author keywords

Bioengineered; Host defense peptide; Innate immunity; Knock out; Transgenics

Indexed keywords

ALPHA DEFENSIN; BACTERIUM LIPOPOLYSACCHARIDE; BETA DEFENSIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; CONCANAVALIN A; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; MATRILYSIN; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; PEPTIDOGLYCAN RECOGNITION PROTEIN; POLYPEPTIDE ANTIBIOTIC AGENT; SECRETORY LEUKOCYTE PROTEINASE INHIBITOR; TOLL LIKE RECEPTOR 2;

ADAPTIVE IMMUNITY; BIOENGINEERING; HUMAN; IMMUNOMODULATION; INFECTION; INFLAMMATORY DISEASE; INNATE IMMUNITY; MOLECULAR BIOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TISSUE ENGINEERING; TRANSGENIC ANIMAL; TUMOR IMMUNITY;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; ANTIMICROBIAL CATIONIC PEPTIDES; BIOENGINEERING; DISEASE; ORGAN SPECIFICITY;

ANIMALIA;

EID: 79151483907     PISSN: 0302766X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00441-010-1075-4     Document Type: Review

References (124)

1. KM Aberg MQ Man RL Gallo T Ganz D Crumrine BE Brown, et al. 2008 Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers J Invest Dermatol 128 917 925 1:CAS:528: DC%2BD1cXjtFOms70%3D 17943185 10.1038/sj.jid.5701099 (Pubitemid 351374295)
2. B Agerberth J Charo J Werr B Olsson F Idali L Lindbom, et al. 2000 The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations Blood 96 3086 3093 1:CAS:528:DC%2BD3cXnslGnt74%3D 11049988
3. R Bals DJ Weiner AD Moscioni RL Meegalla JM Wilson 1999 Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide Infect Immun 67 6084 6089 1:CAS:528:DyaK1MXntV2ru7k%3D 10531270
4. K Bdeir AA Higazi I Kulikovskaya M Christofidou-Solomidou SA Vinogradov T Allen, et al. 2010 Neutrophil alpha-defensins cause lung injury by disrupting the capillary-epithelial barrier Am J Respir Crit Care Med 181 935 946 20093642 10.1164/rccm.200907-1128OC
5. P Bergman L Johansson H Wan A Jones RL Gallo GH Gudmundsson, et al. 2006 Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection Infect Immun 74 6982 6991 1:CAS:528:DC%2BD28XhtlWgs7fO 17030578 10.1128/IAI.01043-06 (Pubitemid 44913173)
6. M Boirivant W Strober 2007 The mechanism of action of probiotics Curr Opin Gastroenterol 23 679 692 17906447 10.1097/MOG.0b013e3282f0cffc (Pubitemid 47508800)
7. HG Boman 1991 Antibacterial peptides: key components needed in immunity Cell 65 205 207 1:CAS:528:DyaK3MXit1Oju70%3D 2015623 10.1016/0092-8674(91)90154- Q
8. HG Boman 2003 Antibacterial peptides: basic facts and emerging concepts J Intern Med 254 197 215 1:CAS:528:DC%2BD3sXnvFejtr8%3D 12930229 10.1046/j.1365-2796.2003.01228.x (Pubitemid 37070221)
9. DM Bowdish DJ Davidson MG Scott RE Hancock 2005 Immunomodulatory activities of small host defense peptides Antimicrob Agents Chemother 49 1727 1732 1:CAS:528:DC%2BD2MXktFSnsbc%3D 15855488 10.1128/AAC.49.5.1727-1732.2005 (Pubitemid 40631581)
10. KA Brogden M Ackermann KM Huttner 1997 Small, anionic, and charge-neutralizing propeptide fragments of zymogens are antimicrobial Antimicrob Agents Chemother 41 1615 1617 1:CAS:528:DyaK2sXktlyqs70%3D 9210699
11. KA Brogden M Ackermann KM Huttner 1998 Detection of anionic antimicrobial peptides in ovine bronchoalveolar lavage fluid and respiratory epithelium Infect Immun 66 5948 5954 1:CAS:528:DyaK1cXnvVCgsrg%3D 9826377
12. KA Brogden M Ackermann PB McCray Jr KM 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 1:CAS:528:DyaK1MXkvVKltLs%3D 10417200
13. AS Buchau S Morizane J Trowbridge J Schauber P Kotol JD Bui RL Gallo 2010 The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth J Immunol 184 369 378 19949065 10.4049/jimmunol. 0902110 1:CAS:528:DC%2BD1MXhsFOnsLnF
14. SJ Bultman EJ Michaud RP Woychik 1992 Molecular characterization of the mouse agouti locus Cell 71 1195 1204 1:CAS:528:DyaK3sXlslGjsLo%3D 1473152 10.1016/S0092-8674(05)80067-4 (Pubitemid 23016553)
15. SI Candille CB Kaelin BM Cattanach B Yu DA Thompson MA Nix, et al. 2007 A -defensin mutation causes black coat color in domestic dogs Science 318 1418 1423 1:CAS:528:DC%2BD2sXhtlGmtLbK 17947548 10.1126/science.1147880 (Pubitemid 350208947)
16. M Carretero M Del Río M García MJ Escámez I Mirones L Rivas, et al. 2004 A cutaneous gene therapy approach to treat infection through keratinocyte-targeted overexpression of antimicrobial peptides FASEB 18 1931 1933 1:CAS:528:DC%2BD2cXhtVKktLjE
17. YR Chan JS Liu DA Pociask M Zheng TA Mietzne T Berger, et al. 2009 Lipocalin 2 is required for pulmonary host defense against Klebsiella infection J Immunol 182 4947 4956 1:CAS:528:DC%2BD1MXjvFOisr4%3D 19342674 10.4049/jimmunol.0803282
18. QX Chen C Lv LX Huang BL Cheng GH Xie SJ Wu XM Fang 2007 Genomic variations within DEFB1 are associated with the susceptibility to and the fatal outcome of severe sepsis in Chinese Han population Genes Immun 8 439 443 1:CAS:528:DC%2BD2sXotVOhsro%3D 17508030 10.1038/sj.gene.6364401 (Pubitemid 47163106)
19. QCK Cheung PV Turner C Song D Wu HY Cai JIK MacInnes J Li 2008 Enhanced resistance to bacterial infection in protegrin-1 transgenic mice Antimicrob Agents Chemother 52 1812 1819 1:CAS:528:DC%2BD1cXls1aju7g%3D 18316527 10.1128/AAC.01530-07 (Pubitemid 351614677)
20. Q Chen M Hakimi S Wu Y Jin B Cheng H Wang, et al. 2010 Increased genomic copy number of DEFA1/DEFA3 is associated with susceptibility to severe sepsis in Chinese Han population Anesthesiology 112 1428 1434 1:CAS:528: DC%2BC3cXmsFSltrc%3D 20502117 10.1097/ALN.0b013e3181d968eb
21. V Chhajlani JES Wikberg 1992 Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA FEBS Lett 309 417 420 1:CAS:528:DyaK3sXkvVKgtbk%3D 1516719 10.1016/0014-5793(92)80820-7
22. M Chromek Z Slamová P Bergman L Kovács L Podracká I Ehrén, et al. 2006 The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection Nat Med 12 636 641 1:CAS:528:DC%2BD28XltlOjsbo%3D 16751768 10.1038/nm1407 (Pubitemid 43865231)
23. CD Ciornei T Sigurdardóttir A Schmidtchen M Bodelsson 2005 Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37 Antimicrob Agents Chemother 49 2845 2850 1:CAS:528:DC%2BD2MXlvFSls70%3D 15980359 10.1128/AAC.49.7.2845-2850.2005 (Pubitemid 40917601)
24. LL Clarke LR Gawenis EM Bradford LM Judd KT Boyle JE Simpson, et al. 2004 Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice Am J Physiol Gastrointest Liver Physiol 286 G1050 G1058 1:CAS:528:DC%2BD2cXkvFGjtL4%3D 14715526 10.1152/ajpgi.00393.2003 (Pubitemid 38715669)
25. DA Devine 2003 Antimicrobial peptides in defence of the oral and respiratory tracts Mol Immunol 40 431 443 1:CAS:528:DC%2BD3sXnvF2qsLk%3D 14568389 10.1016/S0161-5890(03)00162-7 (Pubitemid 37244036)
26. A Di Nardo MH Braf KR Taylor C Na RD Granstein JE McInturff, et al. 2007 Cathelicidin antimicrobial peptides block dendritic cell TLR4 activation and allergic contact sensitization J Immunol 178 1829 1834 17237433
27. DL Draper DV Landers MA Krohn SL Hillier HC Wiesenfeld RP Heine 2000 Levels of vaginal secretory leukocyte protease inhibitor are decreased in women with lower reproductive tract infections Am J Obstet Gynecol 183 1243 1248 1:CAS:528:DC%2BD3cXovVegur0%3D 11084573 10.1067/mob.2000.107383
28. TM Eagan JK Damås T Ueland M Voll-Aanerud TE Mollnes JA Hardie PS Bakke P Aukrust 2000 Neutrophil gelatinase associated lipocalin: a biomarker in chronic obstructive pulmonary disease Chest 138 888 895 10.1378/chest.09-2718
29. S Elahi RM Buchanan S Attah-Poku HG Townsend LA Babiuk V Gerdt 2006 The host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets Infect Immun 74 2338 2352 1:CAS:528: DC%2BD28XjsVWhsbk%3D 16552064 10.1128/IAI.74.4.2338-2352.2006
30. A Fahlgren S Hammarstrom A Danielsson ML Hammarstrom 2004 beta-Defensin-3 and -4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis Clin Exp Immunol 137 379 385 1:CAS:528:DC%2BD2cXntVKju7k%3D 15270856 10.1111/j.1365-2249.2004.02543.x (Pubitemid 39013085)
31. AJ Fales-Williams JM Gallup R Ramírez-Romero KA Brogden MR Ackermann 2002 Increased anionic peptide distribution and intensity during progression and resolution of bacterial pneumonia Clin Diagn Lab Immunol 9 28 32 1:CAS:528:DC%2BD38XnsVyqug%3D%3D 11777825
32. N Fernandez-Jimenez A Castellanos-Rubio L Plaza-Izurieta G Gutierrez L Castaño JC Vitoria JR Bilba 2010 Analysis of Beta-defensin and Toll-like receptor gene copy number variation in celiac disease Hum Immunol 71 833 836 1:CAS:528:DC%2BC3cXovFert7g%3D 20483368 10.1016/j.humimm.2010.05.012
33. BB Finlay RE Hancock 2004 Can innate immunity be enhanced to treat microbial infections? Nat Rev Microbiol 2 497 504 1:CAS:528:DC%2BD2cXktVyisr0%3D 15152205 10.1038/nrmicro908 (Pubitemid 39200016)
34. KA Gallo GL Johnson 2002 Mixed-lineage kinase control of JNK and p38 MAPK pathways Nat Rev Mol Cell Biol 3 663 672 1:CAS:528:DC%2BD38Xmslagu7o%3D 12209126 10.1038/nrm906 (Pubitemid 34987787)
35. RL Gallo M Murakami T Ohtake M Zaiou 2002 Biology and clinical relevance of naturally occurring antimicrobial peptides J Allergy Clin Immunol 110 823 831 1:CAS:528:DC%2BD3sXlvFegsQ%3D%3D 12464945 10.1067/mai.2002.129801 (Pubitemid 36005866)
36. T Gambichler M Skrygan NS Tomi N Othlinghaus NH Brockmeyer P Altmeyer A Kreuter 2008 Differential mRNA expression of antimicrobial peptides and proteins in atopic dermatitis as compared to psoriasis vulgaris and healthy skin Int Arch Allergy Immunol 147 17 24 1:CAS:528:DC%2BD1cXpvFGmsrc%3D 18446049 10.1159/000128582
37. T Ganz JA Metcalf JI Gallin LA Boxer RI Lehrer 1988 Microbicidal/ cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and "specific" granule deficiency J Clin Invest 82 552 556 1:CAS:528:DyaL1cXlt1Kru7g%3D 2841356 10.1172/JCI113631
38. S Ghali KA Bhatt MP Dempsey DM Jones S Singh S Aarabi, et al. 2009 Treating chronic wound infections with genetically modified free flaps Plast Reconstr Surg 123 1157 1168 1:CAS:528:DC%2BD1MXjvVOlsL4%3D 19337084 10.1097/PRS.0b013e31819f25a4
39. A Ghosh S Lee R Dziarski S Chakravarti 2009 A novel antimicrobial peptidoglycan recognition protein in the cornea Invest Ophthalmol Vis Sci 50 4185 4191 19387073 10.1167/iovs.08-3040
40. GH Gudmundsson B Agerberth 1999 Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system J Immunol Meth 232 45 54 1:CAS:528:DC%2BD3cXotVem 10.1016/S0022-1759(99)00152-0 (Pubitemid 30017764)
41. RE Hancock 2001 Cationic peptides: effectors in innate immunity and novel antimicrobials Lancet Infect Dis 1 156 164 1:CAS:528:DC%2BD38XltVOnsbk%3D 11871492 10.1016/S1473-3099(01)00092-5 (Pubitemid 33586049)
42. REW Hancock R Lehrer 1998 Cationic peptides: a new source of antibiotics Trends Biotechnol 16 82 88 1:CAS:528:DyaK1cXht1Snsrg%3D 9487736 10.1016/S0167-7799(97)01156-6 (Pubitemid 28055477)
43. RE Hancock MG Scott 2000 The role of antimicrobial peptides in animal defenses Proc Natl Acad Sci USA 97 8856 8861 1:CAS:528:DC%2BD3cXls12ltLg%3D 10922046 10.1073/pnas.97.16.8856 (Pubitemid 30626637)
44. J Harder J Bartels E Christophers JM Schroder 2001 Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic J Biol Chem 276 5707 5713 1:CAS:528:DC%2BD3MXhs1Kmtrg%3D 11085990 10.1074/jbc.M008557200
45. JD Heilborn MF Nilsson G Kratz G Weber O Sørensen N Borregaard M Ståhle-Bäckdahl 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 1:CAS:528:DC%2BD3sXitlOht78%3D 12603850 10.1046/j.1523-1747.2003.12069.x (Pubitemid 36298423)
46. JD Heilborn MF Nilsson CI Jimenez B Sandstedt N Borregaard E Tham, et al. 2005 Antimicrobial protein hCAP18/LL-37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells Int J Cancer 114 713 719 1:CAS:528:DC%2BD2MXitl2qurw%3D 15609314 10.1002/ijc.20795 (Pubitemid 40344432)
47. T Hirsch M Spielmann B Zuhaili M Fossum M Metzig T Koehler, et al. 2009 Human beta-defensin-3 promotes wound healing in infected diabetic wounds J Gene Med 11 220 228 1:CAS:528:DC%2BD1MXksVWgsLs%3D 19115333 10.1002/jgm.1287
48. AW Horne SJ Stock AE King 2008 Innate immunity and disorders of the female reproductive tract Reproduction 135 739 749 1:CAS:528: DC%2BD1cXnsVOksr8%3D 18502890 10.1530/REP-07-0564 (Pubitemid 351837387)
49. MD Howell JF Jones KO Kisich JE Streib RL Gallo DY Leung 2004 Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum J Immunol 172 1763 1767 1:CAS:528:DC%2BD2cXptl2iug%3D%3D 14734759
50. MD Howell A Wollenberg RL Gallo M Flaig JE Streib C Wong, et al. 2006 Cathelicidin deficiency predisposes to eczema herpeticum J Allergy Clin Immunol 117 836 841 1:CAS:528:DC%2BD28XjslelsLo%3D 16630942 10.1016/j.jaci.2005.12.1345
51. J-C Hsieh CYC Pan JY Chen 2010 Tilapia hepcidin (TH)2-3 as a transgene in transgenic fish enhances resistance to Vibrio vulnificus infection and causes variations in immune-related genes after infection by different bacterial species Fish Shellfish Immunol 29 430 439 1:CAS:528:DC%2BC3cXos1KitL4%3D 20470893 10.1016/j.fsi.2010.05.001
52. LC Huang RY Reins RL Gallo AM McDermott 2007 Cathelicidin-deficient (Cnlp -/-) mice show increased susceptibility to Pseudomonas aeruginosa keratitis Invest Ophthalmol Vis Sci 48 4498 4508 17898271 10.1167/iovs.06-0320 (Pubitemid 47251409)
53. M Iimura RL Gallo K Hase Y Miyamoto L Eckmann MF Kagnoff 2005 Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens J Immunol 174 4901 4907 1:CAS:528:DC%2BD2MXivFKiurY%3D 15814717
54. F Jacobsen D Mittler T Hirsch A Gerhards M Lehnhardt B Voss, et al. 2005 Transient cutaneous adenoviral gene therapy with human host defense peptide hCAP-18/LL-37 is effective for the treatment of burn wound infections Gene Ther 12 1494 1502 1:CAS:528:DC%2BD2MXhtVKhsL%2FN 15973442 10.1038/sj.gt.3302568 (Pubitemid 41508674)
55. PAM Jansen D Rodijk-Olthuis EJ Hollox M Kamsteeg GS Tjabringa GJ de Jongh, et al. 2009 Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin PLoS ONE 4 e4725 19266104 10.1371/journal.pone.0004725 1:CAS:528:DC%2BD1MXjtFOqu7k%3D
56. AE King HO Critchley RW Kelly 2000 Presence of secretory leukocyte protease inhibitor in human endometrium and first trimester decidua suggests an antibacterial protective role Mol Hum Reprod 6 191 196 1:CAS:528: DC%2BD3cXhtlaisb0%3D 10655462 10.1093/molehr/6.2.191
57. AE King HO Critchley RW Kelly 2003 Innate immune defences in the human endometrium Reprod Biol Endocrinol 1 116 14641912 10.1186/1477-7827-1-116 (Pubitemid 39130409)
58. H Klungland DI Vage 2003 Pigmentary switches in domestic animal species Ann NY Acad Sci 994 331 338 1:CAS:528:DC%2BD3sXmtVCktb0%3D 12851333 10.1111/j.1749-6632.2003.tb03197.x
59. R Koczulla G von Degenfeld C Kupatt F Krötz S Zahler T Gloe, et al. 2003 An angiogenic role for the human peptide antibiotic LL-37/hCAP-18 J Clin Invest 111 1665 1672 1:CAS:528:DC%2BD3sXksVKrsL4%3D 12782669
60. R Lande J Gregorio V Facchinetti B Chatterjee YH Wang B Homey, et al. 2007 Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide Nature 449 564 569 1:CAS:528:DC%2BD2sXhtFagtL7K 17873860 10.1038/nature06116 (Pubitemid 47525141)
61. PM LeBlanc G Yeretssian N Rutherford K Doiron A Nadiri L Zhu, et al. 2008 Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity Cell Host Microbe 3 146 157 1:CAS:528: DC%2BD1cXktVensrw%3D 18329614 10.1016/j.chom.2008.02.004 (Pubitemid 351325760)
62. PH Lee T Ohtake M Zaiou JA Murakami JA Rudisill KH Lin RL Gallo 2005 Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection Proc Natl Acad Sci USA 102 3750 3755 1:CAS:528:DC%2BD2MXisVOgtrw%3D 15728389 10.1073/pnas.0500268102 (Pubitemid 40354683)
63. AB Lentsch JA Jordan BJ Czermak KM Diehl EM Younkin V Sarma PA Ward 1999 Inhibition of NF-kappaB activation and augmentation of IkappaBbeta by secretory leukocyte protease inhibitor during lung inflammation Am J Pathol 154 239 247 1:CAS:528:DyaK1MXnsFGitg%3D%3D 9916938
64. P Levinson R Kaul J Kimani E Ngugi S Moses KS MacDonald, et al. 2009 Levels of innate immune factors in genital fluids: association of alpha defensins and LL-37 with genital infections and increased HIV acquisition AIDS 23 309 317 1:CAS:528:DC%2BD1MXht1Gmtrc%3D 19114868 10.1097/QAD.0b013e328321809c
65. D Li J Li Y Duan X Zhou 2004 Expression of LL-37, human beta defensin-2, and CCR6 mRNA in patients with psoriasis vulgaris J Huazhong Univ Sci Technolog Med Sci 24 404 406 15587410 10.1007/BF02861879
66. C-Y Lin PH-Y Yang CLY Kao HI Huang HJ Tsai 2010 Transgenic zebrafish eggs containing bactericidal peptide is a novel food supplement enhancing resistance to pathogenic infection of fish Fish Shellfish Immunol 28 419 427 1:CAS:528:DC%2BC3cXit1Kjtbw%3D 19944764 10.1016/j.fsi.2009.11.019
67. Marre ML, Darcy CT, Yinh J, Akira S, Uematsu S, Steere AC, Hu LT (2010) The role of adrenomedullin in Lyme disease. Infect Immun (in press)
68. M Mathews HP Jia JM Guthmiller G Losh S Graham GK Johnson, et al. 1999 Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands Infect Immun 67 2740 2745 1:CAS:528:DyaK1MXjsFSgtbY%3D 10338476
69. Matzner M, Al Samie AR, Winkler HM, Nemeth J, Grasnek A, Indra A, et al (2010) Low serum levels of cathelicidin LL-37 in leprosy. Acta Trop (in press)
70. JW McMichael AI Maxwell K Hayashi K Taylor WA Wallace JR Govan, et al. 2005 Antimicrobial activity of murine lung cells against Staphylococcus aureus is increased in vitro and in vivo after elafin gene transfer Infect Immun 73 3609 3617 1:CAS:528:DC%2BD2MXkvFCnsLs%3D 15908390 10.1128/IAI.73.6.3609-3617. 2005 (Pubitemid 40745905)
71. N Mookherjee KL Brown DM Bowdish S Doria R Falsafi K Hokamp, et al. 2006 Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37 J Immunol 176 2455 2464 1:CAS:528: DC%2BD28XpvV2rsQ%3D%3D 16456005
72. Y Morioka K Yamasaki D Leung RL Gallo 2008 Cathelicidin antimicrobial peptides inhibit hyaluronan-induced cytokine release and modulate chronic allergic dermatitis J Immunol 181 3915 3922 1:CAS:528:DC%2BD1cXhtVKntLjF 18768846
73. C Moser DJ Weiner E Lysenko R Bals JN Weiser JM Wilson 2002 Beta-defensin 1 contributes to pulmonary innate immunity in mice Infect Immun 70 3068 3072 1:CAS:528:DC%2BD38XktFGiurg%3D 12010999 10.1128/IAI.70.6.3068-3072.2002 (Pubitemid 34564168)
74. C Munk G Wei OO Yang AJ Waring W Wang T Hong, et al. 2003 The theta-defensin, retrocyclin, inhibits HIV-1 entry AIDS Res Hum Retroviruses 19 875 881 14585219 10.1089/088922203322493049 1:CAS:528:DC%2BD3sXotlWrur0%3D (Pubitemid 37338913)
75. M Murakami T Ohtake RA Dorschner RL Gallo 2002 Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva J Dent Res 81 845 850 1:CAS:528:DC%2BD38Xps1Khs78%3D 12454100 10.1177/154405910208101210
76. M Murakami T Ohtake RA Dorschner B Schittek C Garbe RL Gallo 2002 Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin J Invest Dermatol 119 1090 1095 1:CAS:528: DC%2BD38XpslCrt7k%3D 12445197 10.1046/j.1523-1747.2002.19507.x (Pubitemid 35434172)
77. M Murakami RA Dorschner LJ Stern KH Lin RL Gallo 2005 Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk Pediatr Res 57 10 15 1:CAS:528:DC%2BD2cXhtFejurbJ 15531744 10.1203/01.PDR.0000148068.32201.50 (Pubitemid 40039886)
78. TX Nguyen AM Cole RI Lehrer 2003 Evolution of primate theta-defensins: a serpentine path to a sweet tooth Peptides 24 1647 1654 1:CAS:528: DC%2BD2cXhtFWmtLg%3D 15019196 10.1016/j.peptides.2003.07.023 (Pubitemid 38198072)
79. G Nicolas M Bennoun A Porteu S Mativet C Beaumont B Grandchamp, et al. 2002 Severe iron deficiency anemia in transgenic mice expressing liver hepcidin Proc Natl Acad Sci USA 99 4596 4601 1:CAS:528:DC%2BD38XivFShu7o%3D 11930010 10.1073/pnas.072632499 (Pubitemid 34286030)
80. V Nizet T Ohtake X Lauth J Trowbridge J Rudisill RA Dorschner, et al. 2001 Innate antimicrobial peptide protects the skin from invasive bacterial infection Nature 414 454 457 1:CAS:528:DC%2BD3MXovFamsbY%3D 11719807 10.1038/35106587 (Pubitemid 34173727)
81. O Norkina TG Burnett RC De Lisle 2004 Bacterial overgrowth in the cystic fibrosis transmembrane conductance regulator null mouse small intestine Infect Immun 72 6040 6049 1:CAS:528:DC%2BD2cXotFaks7g%3D 15385508 10.1128/IAI.72.10. 6040-6049.2004 (Pubitemid 39303719)
82. PY Ong T Ohtake C Brandt I Strickland M Boguniewicz T Ganz, et al. 2002 Endogenous antimicrobial peptides and skin infections in atopic dermatitis N Engl J Med 347 1151 1160 1:CAS:528:DC%2BD38XnslShsb0%3D 12374875 10.1056/NEJMoa021481
83. A Oren T Ganz L Liu T Meerloo 2003 In human epidermis, beta-defensin 2 is packaged in lamellar bodies Exp Mol Pathol 74 180 182 1:CAS:528: DC%2BD3sXjtFWmsLk%3D 12710950 10.1016/S0014-4800(02)00023-0 (Pubitemid 36438667)
84. J-M Otte KM Kiehne KH Herzig 2003 Antimicrobial peptides in innate immunity of the human intestine J Gastroenterol 38 717 726 1:CAS:528: DC%2BD3sXntlShuro%3D 14505124 10.1007/s00535-003-1136-5 (Pubitemid 37161334)
85. AJ Ouellette 2005 Paneth cell alpha-defensins: peptide mediators of innate immunity in the small intestine Springer Semin Immunopathol 27 133 146 1:CAS:528:DC%2BD2MXhtVSjtrjF 15931529 10.1007/s00281-005-0202-x (Pubitemid 41291621)
86. P Pacora E Maymon MT Gervasi R Gomez SS Edwin BH Yoon R Romero 2000 Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes Am J Obstet Gynecol 183 904 910 1:CAS:528:DC%2BD3cXot1Skt74%3D 11035335 10.1067/mob.2000.108882
87. V Pak A Budikhina M Pashenkov B Pinegin 2007 Neutrophil activity in chronic granulomatous disease Adv Exp Med Biol 601 69 74 17712993 10.1007/978-0-387-72005-0-7
88. KC Peng CY Pan HN Chou JY Chen 2010 Using an improved Tol2 transposon system to produce transgenic zebrafish with epinecidin-1 which enhanced resistance to bacterial infection Fish Shellfish Immunol 28 905 917 1:CAS:528:DC%2BC3cXlt1Wqt70%3D 20153437 10.1016/j.fsi.2010.02.003
89. SM Phadke B Deslouches SE Hileman RC Montelaro HC Wiesenfeld TA Mietzner 2005 Antimicrobial peptides in mucosal secretions: the importance of local secretions in mitigating infection J Nutr 135 1289 1293 1:CAS:528: DC%2BD2MXktFKiuro%3D 15867326
90. K Pillay A Coutsoudis AK Agadzi-Naqvi L Kuhn HM Coovadia EN Janoff 2001 Secretory leukocyte protease inhibitor in vaginal fluids and perinatal human immunodeficiency virus type 1 transmission J Infect Dis 183 653 656 1:CAS:528:DC%2BD3MXhsVWrtbs%3D 11170993 10.1086/318535 (Pubitemid 32147523)
91. K Pütsep G Carlsson HG Boman M Andersson 2002 Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study Lancet 360 1144 1149 12387964 10.1016/S0140-6736(02)11201-3 (Pubitemid 35246490)
92. LS Robbins JH Nadeau KR Johnson MA Kelly L Roselli-Rehfuss E Baack MA Kelly, et al. 1993 Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function Cell 72 827 834 1:CAS:528:DyaK3sXit1Ohsr4%3D 8458079 10.1016/0092-8674(93)90572-8 (Pubitemid 23110225)
93. CN Roy HH Mak I Akpan G Losyev D Zurakowski NC Andrews 2007 Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation Blood 109 4038 4044 1:CAS:528:DC%2BD2sXkvFCiu70%3D 17218383 10.1182/blood-2006-10-051755 (Pubitemid 46641759)
94. J-M Sallenave GA Cunningham RM James G McLachlan C Haslett 2003 Regulation of pulmonary and systemic bacterial lipopolysaccharide responses in transgenic mice expressing human elafin Infect Immun 71 3766 3774 1:CAS:528:DC%2BD3sXms1Wjtrc%3D 12819058 10.1128/IAI.71.7.3766-3774.2003 (Pubitemid 36753697)
95. NH Salzman D Ghosh KM Huttner Y Paterson C Bevins 2003 Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin Nature 422 522 526 1:CAS:528:DC%2BD3sXisFCisrs%3D 12660734 10.1038/nature01520 (Pubitemid 36433647)
96. NH Salzman K Hung D Haribhai H Chu J Karlsson-Sjöberg E Amir, et al. 2010 Enteric defensins are essential regulators of intestinal microbial ecology Nat Immunol 11 76 83 1:CAS:528:DC%2BD1MXhtlSqsbzF 19855381 10.1038/ni.1825
97. D Sawamura M Goto A Shibaki M Akiyama JR McMillan Y Abiko H Shimizu 2005 Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection Gene Ther 12 857 861 1:CAS:528:DC%2BD2MXjvFeksbs%3D 15729370 10.1038/sj.gt.3302472 (Pubitemid 40753978)
98. J Schauber RL Gallo 2008 The vitamin D pathway: a new target for control of the skin's immune response? Exp Dermatol 17 633 639 1:CAS:528: DC%2BD1cXps1OntLw%3D 18573153 10.1111/j.1600-0625.2008.00768.x (Pubitemid 352044354)
99. JM Schroder J Harder 2006 Antimicrobial skin peptides and proteins Cell Mol Life Sci 63 469 486 1:CAS:528:DC%2BD28XisVajsbY%3D 16416029 10.1007/s00018-005-5364-0
100. Y Shai 1999 Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides Biochim Biophys Acta 1462 55 70 1:CAS:528:DyaK1MXnslymu78%3D 10590302 10.1016/S0005-2736(99)00200-X
101. Q Shu Z Shi Z Zhao Z Chen H Yao Q Chen, et al. 2006 Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of beta-defensin-2 in rats Shock 26 365 371 1:CAS:528: DC%2BD28XhtFWlu7%2FJ 16980883 10.1097/01.shk.0000224722.65929.58 (Pubitemid 44402021)
102. AJ Simpson WA Wallace ME Marsden JR Govan DJ Porteous C Haslett JM Sallenave 2001 Adenoviral augmentation of elafin protects the lung against acute injury mediated by activated neutrophils and bacterial infection J Immunol 167 1778 1786 1:CAS:528:DC%2BD3MXls1Wrtr8%3D 11466403
103. OE Sorensen L Gram AH Johnsen E Andersson S Bangsbøll GS Tjabringa, et al. 2003 Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina J Biol Chem 278 28540 28546 1:CAS:528:DC%2BD3sXlsl2ntLg%3D 12759353 10.1074/jbc.M301608200 (Pubitemid 36935758)
104. TD Starner B Agerberth GH Gudmundsson PB McCray Jr 2005 Expression and activity of beta-defensins and LL-37 in the developing human lung J Immunol 174 1608 1615 1:CAS:528:DC%2BD2MXlsFyltw%3D%3D 15661923
105. Y Sumikawa H Asada K Hoshino H Azukizawa I Katayama S Akira S Itami 2006 Induction of beta-defensin 3 in keratinocytes stimulated by bacterial lipopeptides through toll-like receptor 2 Microbes Infect 8 1513 1521 1:CAS:528:DC%2BD28XlvFGqtrY%3D 16697678 10.1016/j.micinf.2006.01.008 (Pubitemid 44192354)
106. CL Thomas-Virnig JM Centanni CE Johnston LK He SJ Schlosser KF Van Winkle, et al. 2009 Inhibition of multidrug-resistant Acinetobacter baumannii by nonviral expression of hCAP-18 in a bioengineered human skin tissue Mol Ther 17 562 569 1:CAS:528:DC%2BD1MXhtlygtr0%3D 19190595 10.1038/mt.2008.289
107. GS Tjabringa J Aarbiou DK Ninaber JW Drijfhout OE Sørensen N Borregaard, et al. 2003 The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor J Immunol 171 6690 6696 1:CAS:528:DC%2BD3sXpsV2rt7c%3D 14662872
108. S Tokumaru K Sayama Y Shirakata H Komatsuzawa K Ouhara Y Hanakawa, et al. 2005 Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37 J Immunol 175 4662 4668 1:CAS:528:DC%2BD2MXhtVWltbnM 16177113
109. EV Valore CH Park AJV Quayle KR Wiles PB McCray Jr T Ganz 1998 Human beta-defensin-1: an antimicrobial peptide of urogenital tissues J Clin Invest 101 1633 1642 1:CAS:528:DyaK1cXisV2qsrg%3D 9541493 10.1172/JCI1861
110. P Vora A Youdim LS Thomas M Fukata SY Tesfay K Lukasek, et al. 2004 Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells J Immunol 173 5398 5405 1:CAS:528:DC%2BD2cXos1Giur0%3D 15494486
111. W Wang SM Owen DL Rudolph AM Cole T Hong AJ Waring, et al. 2004 Activity of alpha- and theta-defensins against primary isolates of HIV-1 J Immunol 173 515 520 1:CAS:528:DC%2BD2cXltVaitLs%3D 15210812
112. G Weber CI Chamorro F Granath A Liljegren S Zreika Z Saidak, et al. 2009 Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer Breast Cancer Res 11 R6 19183447 10.1186/bcr2221 1:CAS:528:DC%2BD1MXis1Kmsbw%3D
113. J Wehkamp J Harder M Weichenthal M Schwab E Schäffeler M Schlee, et al. 2004 NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression Gut 53 1658 1664 1:CAS:528:DC%2BD2cXhtVajtrvK 15479689 10.1136/gut.2003.032805 (Pubitemid 39434112)
114. J Wehkamp NH Salzman E Porter S Nuding M Weichenthal RE Petras, et al. 2005 Reduced Paneth cell alpha-defensins in ileal Crohn's disease Proc Natl Acad Sci USA 102 18129 18134 1:CAS:528:DC%2BD2MXhtlersrrI 16330776 10.1073/pnas.0505256102 (Pubitemid 41798513)
115. SH White WC Wimley ME Selsted 1995 Structure, function, and membrane integration of defensins Curr Opin Struct Biol 5 521 527 1:CAS:528: DyaK2MXotF2lsLc%3D 8528769 10.1016/0959-440X(95)80038-7
116. CL Wilson AJ Ouellette DP Satchell T Ayabe YS López-Boado JL Stratman, et al. 1999 Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense Science 286 113 117 1:CAS:528:DyaK1MXmsFehurc%3D 10506557 10.1126/science.286.5437.113 (Pubitemid 29484488)
117. JA Wolfram D Diaconu DA Hatala J Rastegar DA Knutsen A Lowther, et al. 2009 Keratinocyte but not endothelial cell-specific overexpression of Tie2 leads to the development of psoriasis Am J Pathol 174 1443 1458 1:CAS:528: DC%2BD1MXksVOkurg%3D 19342373 10.2353/ajpath.2009.080858
118. Y Yamaguchi T Nagase T Tomita K Nakamura S Fukuhara T Amano, et al. 2007 Beta-defensin overexpression induces progressive muscle degeneration in mice Am J Physiol Cell Physiol 292 C2141 C2149 1:CAS:528:DC%2BD2sXmvF2ms7w%3D 17215327 10.1152/ajpcell.00295.2006 (Pubitemid 47080520)
119. K Yamasaki J Schauber A Coda H Lin RA Dorschner Nm Schechter, et al. 2006 Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin FASEB J 20 2068 2080 1:CAS:528:DC%2BD28XhtVyhu7fL 17012259 10.1096/fj.06-6075com (Pubitemid 44953906)
120. K Di Yamasaki A Nardo A Bardan M Murakami T Ohtake A Coda, et al. 2007 Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea Nat Med 13 975 980 1:CAS:528:DC%2BD2sXos1Cjsbs%3D 17676051 10.1038/nm1616 (Pubitemid 47222043)
121. C-C Yen CYC Lin KY Chong TCC Tsai CJ Shen MF Lin, et al. 2009 Lactoferrin as a natural regimen for selective decontamination of the digestive tract: recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonates from pathogenic challenge in the gastrointestinal tract J Infect Dis 199 590 598 1:CAS:528:DC%2BD1MXislClurc%3D 19125673 10.1086/596212
122. M Zanetti 2004 Cathelicidins, multifunctional peptides of the innate immunity J Leukoc Biol 75 39 48 12960280 10.1189/jlb.0403147 1:CAS:528:DC%2BD2cXmsFelsA%3D%3D (Pubitemid 38166778)
123. M Zasloff 2002 Innate immunity, antimicrobial peptides, and protection of the oral cavity Lancet 360 1116 1117 12387955 10.1016/S0140-6736(02)11239-6 (Pubitemid 35246481)
124. SM Zughaier WM Shafer DS Stephens 2005 Antimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release but amplify respiratory burst response in human and murine macrophages Cell Microbiol 7 1251 1262 1:CAS:528:DC%2BD2MXps12htb8%3D 16098213 10.1111/j.1462-5822.2005.00549.x (Pubitemid 41179418)