Cationic host defence peptides: Multifaceted role in immune modulation and inflammation

Journal of Innate Immunity

Volumn 4, Issue 4, 2012, Pages 361-370

  Choi, Ka Yee ^a   Chow, Leola N Y ^a   Mookherjee, Neeloffer ^a,b  

^a UNIVERSITY OF MANITOBA   (Canada)

^b UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Antimicrobial peptides; Host defence; Host defence peptides; Immunomodulation; Inflammation

Indexed keywords

ANTIMICROBIAL CATIONIC PEPTIDE; CATHELICIDIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; CATION; CATION TRANSPORT PROTEIN; PR 39; TRANSCRIPTION FACTOR;

ADAPTIVE IMMUNITY; AUTOPHAGY; HOST RESISTANCE; HUMAN; IMMUNOMODULATION; INFLAMMATION; INNATE IMMUNITY; NONHUMAN; PHAGOCYTOSIS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

AMINO ACID SEQUENCE; ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOMODULATION; INFLAMMATION; MOLECULAR SEQUENCE DATA;

EID: 84863331797     PISSN: 1662811X     EISSN: 16628128     Source Type: Journal    
DOI: 10.1159/000336630     Document Type: Review

References (89)

1. Cederlund A, Gudmundsson GH, Agerberth B: Antimicrobial peptides important in innate immunity. FEBS J 2011; 278: 3942-3951.
2. Tossi A, Sandri L: Molecular diversity in gene-encoded, cationic antimicrobial polypeptides. Curr Pharm Des 2002; 8: 743-761.
3. Guani-Guerra E, Santos-Mendoza T, Lugo- Reyes SO, Teran LM: Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol 2010; 135: 1-11.
4. Molhoek EM, van Dijk A, Veldhuizen EJ, Haagsman HP, Bikker FJ: A cathelicidin-2- derived peptide effectively impairs Staphylococcus epidermidis biofilms. Int J Antimicrob Agents 2011; 37: 476-479.
5. Rajanbabu V, Chen JY: Antiviral function of tilapia hepcidin 1-5 and its modulation of immune-related gene expressions against infectious pancreatic necrosis virusIPNV) in Chinook salmon embryoCHSE)-214 cells. Fish Shellfish Immunol 2011; 30: 39-44.
6. Bowdish DM, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock RE: Impact of LL-37 on anti-infective immunity. J Leukoc Biol 2005; 77: 451-459.
7. Arnett E, Lehrer RI, Pratikhya P, Lu W, Seveau S: Defensins enable macrophages to inhibit the intracellular proliferation of Listeria monocytogenes. Cell Microbiol 2011; 13: 635-651.
8. Haines LR, Hancock RE, Pearson TW: Cationic antimicrobial peptide killing of African trypanosomes and Sodalis glossinidius, a bacterial symbiont of the insect vector of sleeping sickness. Vector Borne Zoonotic Dis 2003; 3: 175-186.
9. Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM: Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 1998; 102: 874-880.
10. Scott MG, Dullaghan E, Mookherjee N, Glavas N, Waldbrook M, Thompson A, Wang A, Lee K, Doria S, Hamill P, Yu JJ, Li Y, Donini O, Guarna MM, Finlay BB, North JR, Hancock RE: An anti-infective peptide that selectively modulates the innate immune response. Nat Biotechnol 2007; 25: 465-472.
11. Nijnik A, Madera L, Ma S, Waldbrook M, Elliott MR, Easton DM, Mayer ML, Mullaly SC, Kindrachuk J, Jenssen H, Hancock RE: Synthetic cationic peptide IDR-1002 provides protection against bacterial infections through chemokine induction and enhanced leukocyte recruitment. J Immunol 2010; 184: 2539-2550.
12. Bevins CL, Salzman NH: Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011; 9: 356-368.
13. Gallo RL: Sounding the alarm: multiple functions of host defense peptides. J Invest Dermatol 2008; 128: 5-6.
14. Allaker RP: Host defence peptides - a bridge between the innate and adaptive immune responses. Trans R Soc Trop Med Hyg 2008; 102: 3-4.
15. Mookherjee N, Brown KL, Bowdish DM, Doria S, Falsafi R, Hokamp K, Roche FM, Mu R, Doho GH, Pistolic J, Powers JP, Bryan J, Brinkman FS, Hancock RE: Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 2006; 176: 2455-2464.
16. Diamond G, Beckloff N, Weinberg A, Kisich KO: The roles of antimicrobial peptides in innate host defense. Curr Pharm Des 2009; 15: 2377-2392.
17. Hosokawa I, Hosokawa Y, Komatsuzawa H, Goncalves RB, Karimbux N, Napimoga MH, Seki M, Ouhara K, Sugai M, Taubman MA, Kawai T: Innate immune peptide LL-37 displays distinct expression pattern from betadefensins in inflamed gingival tissue. Clin Exp Immunol 2006; 146: 218-225.
18. Jo EK: Innate immunity to mycobacteria: vitamin D and autophagy. Cell Microbiol 2010; 12: 1026-1035.
19. Hilpert K, Elliott MR, Volkmer-Engert R, Henklein P, Donini O, Zhou Q, Winkler DF, Hancock RE: Sequence requirements and an optimization strategy for short antimicrobial peptides. Chem Biol 2006; 13: 1101-1107.
20. Turner-Brannen E, Choi KY, Lippert DN, Cortens JP, Hancock RE, El-Gabalawy H, Mookherjee N: Modulation of interleukin- 1 -induced inflammatory responses by a synthetic cationic innate defence regulator peptide, IDR-1002, in synovial fibroblasts. Arthritis Res Ther 2011; 13:R129.
21. Wieczorek M, Jenssen H, Kindrachuk J, Scott WR, Elliott M, Hilpert K, Cheng JT, Hancock RE, Straus SK: Structural studies of a peptide with immune modulating and direct antimicrobial activity. Chem Biol 2010; 17: 970-980.
22. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock R: The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 2002; 169: 3883-3891.
23. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ: Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525-528.
24. Nagaoka I, Tamura H, Hirata M: An antimicrobial cathelicidin peptide, human CAP18/ LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptorlike 1 and P2X7. J Immunol 2006; 176: 3044-3052.
25. Bandholtz L, Ekman GJ, Vilhelmsson M, Buentke E, Agerberth B, Scheynius A, Gudmundsson GH: Antimicrobial peptide LL-37 internalized by immature human dendritic cells alters their phenotype. Scand J Immunol 2006; 63: 410-419.
26. Davidson DJ, Currie AJ, Reid GS, Bowdish DM, MacDonald KL, Ma RC, Hancock RE, Speert DP: The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 2004; 172: 1146-1156.
27. Funderburg N, Lederman MM, Feng Z, Drage MG, Jadlowsky J, Harding CV, Weinberg A, Sieg SF: Human-defensin-3 activates professional antigen-presenting cells via toll-like receptors 1 and 2. Proc Natl Acad Sci USA 2007; 104: 18631-18635.
28. Rodriguez-Garcia M, Oliva H, Climent N, Escribese MM, Garcia F, Moran TM, Gatell JM, Gallart T: Impact of alpha-defensins1- 3 on the maturation and differentiation of human monocyte-derived DCs. Concentration- dependent opposite dual effects. Clin Immunol 2009; 131: 374-384.
29. Kin NW, Chen Y, Stefanov EK, Gallo RL, Kearney JF: Cathelin-related antimicrobial peptide differentially regulates T- and B-cell function. Eur J Immunol 2011; 41: 3006-3016.
30. Lillard JW Jr, 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: 651-656.
31. Cirioni O, Giacometti A, Ghiselli R, Bergnach C, Orlando F, Silvestri C, Mocchegiani F, Licci A, Skerlavaj B, Rocchi M, Saba V, Zanetti M, Scalise G: LL-37 protects rats against lethal sepsis caused by gram-negative bacteria. Antimicrob Agents Chemother 2006; 50: 1672-1679.
32. Giacometti A, Cirioni O, Ghiselli R, Bergnach C, Orlando F, D'Amato G, Mocchegiani F, Silvestri C, Del Prete MS, Skerlavaj B, Saba V, Zanetti M, Scalise G: The antimicrobial peptide BMAP-28 reduces lethality in mouse models of staphylococcal sepsis. Crit Care Med 2004; 32: 2485-2490.
33. Shu Q, Shi Z, Zhao Z, Chen Z, Yao H, Chen Q, Hoeft A, Stuber F, Fang X: Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of beta-defensin-2 in rats. Shock 2006; 26: 365-371.
34. Semple F, Macpherson H, Webb S, Cox SL, Mallin LJ, Tyrrell C, Grimes GR, Semple CA, Nix MA, Millhauser GL, Dorin JR: Human - defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF. Eur J Immunol 2011; 41: 3291-3300.
35. Mookherjee N, Hamill P, Gardy J, Blimkie D, Falsafi R, Chikatamarla A, Arenillas DJ, Doria S, Kollmann TR, Hancock RE: Systems biology evaluation of immune responses induced by human host defence peptide LL-37 in mononuclear cells. Mol Biosyst 2009; 5: 483-496.
36. Brown KL, Poon GF, Birkenhead D, Pena OM, Falsafi R, Dahlgren C, Karlsson A, Bylund J, Hancock RE, Johnson P: Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses. J Immunol 2011; 186: 5497-5505.
37. Mookherjee N, Wilson HL, Doria S, Popowych Y, Falsafi R, Yu JJ, Li Y, Veatch S, Roche FM, Brown KL, Brinkman FS, Hokamp K, Potter A, Babiuk LA, Griebel PJ, Hancock RE: Bovine and human cathelicidin cationic host defense peptides similarly suppress transcriptional responses to bacterial lipopolysaccharide. J Leukoc Biol 2006; 80: 1563-1574.
38. Lau YE, Rozek A, Scott MG, Goosney DL, Davidson DJ, Hancock RE: Interaction and cellular localization of the human host defense peptide LL-37 with lung epithelial cells. Infect Immun 2005; 73: 583-591.
39. De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O: LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 2000; 192: 1069-1074.
40. Mookherjee N, Lippert DN, Hamill P, Falsafi R, Nijnik A, Kindrachuk J, Pistolic J, Gardy J, Miri P, Naseer M, Foster LJ, Hancock RE: Intracellular receptor for human host defense peptide LL-37 in monocytes. J Immunol 2009; 183: 2688-2696.
41. Yu HB, Kielczewska A, Rozek A, Takenaka S, Li Y, Thorson L, Hancock RE, Guarna MM, North JR, Foster LJ, Donini O, Finlay BB: Sequestosome- 1/p62 is the key intracellular target of innate defense regulator peptide. J Biol Chem 2009; 284: 36007-36011.
42. Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J, Meller S, Chamilos G, Sebasigari R, Riccieri V, Bassett R, Amuro H, Fukuhara S, Ito T, Liu YJ, Gilliet M: Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci Transl Med 2011; 3: 73ra19.
43. Gilliet M, Lande R: Antimicrobial peptides and self-DNA in autoimmune skin inflammation. Curr Opin Immunol 2008; 20: 401-407.
44. Feldmann M, Maini RN: Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 2003; 9: 1245-1250.
45. Botsios C: Safety of tumour necrosis factor and interleukin-1 blocking agents in rheumatic diseases. Autoimmun Rev 2005; 4: 162-170.
46. Yu J, Mookherjee N, Wee K, Bowdish DM, Pistolic J, Li Y, Rehaume L, Hancock RE: Host defense peptide LL-37, in synergy with inflammatory mediator IL-1beta, augments immune responses by multiple pathways. J Immunol 2007; 179: 7684-7691.
47. Nijnik A, Pistolic J, Wyatt A, Tam S, Hancock RE: Human cathelicidin peptide LL-37 modulates the effects of IFN-gamma on APCs. J Immunol 2009; 183: 5788-5798.
48. Kanda N, Ishikawa T, Kamata M, Tada Y, Watanabe S: Increased serum leucine, leucine- 37 levels in psoriasis: positive and negative feedback loops of leucine, leucine-37 and pro- or anti-inflammatory cytokines. Hum Immunol 2010; 71: 1161-1171.
49. Dombrowski Y, Peric M, Koglin S, Kammerbauer C, Goss C, Anz D, Simanski M, Glaser R, Harder J, Hornung V, Gallo RL, Ruzicka T, Besch R, Schauber J: Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci Transl Med 2011; 3: 82ra38.
50. Yang YH, Wu WK, Tai EK, Wong HP, Lam EK, So WH, Shin VY, Cho CH: The cationic host defense peptide rCRAMP promotes gastric ulcer healing in rats. J Pharmacol Exp Ther 2006; 318: 547-554.
51. Hadley EB, Hancock RE: Strategies for the discovery and advancement of novel cationic antimicrobial peptides. Curr Top Med Chem 2010; 10: 1872-1881.
52. Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L: Neutrophil secretion products pave the way for inflammatory monocytes. Blood 2008;112:1461-1471.
53. Tjabringa GS, Ninaber DK, Drijfhout JW, Rabe KF, Hiemstra PS: Human cathelicidin ll-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors. Int Arch Allergy Immunol 2006; 140:103-112.
54. Yang D, Chen Q, Chertov O, Oppenheim JJ: Human neutrophil defensins selectively chemoattract naive t and immature dendritic cells. J Leukoc Biol 2000;68:9-14.
55. Territo MC, Ganz T, Selsted ME, Lehrer R: Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 1989; 84:2017-2020.
56. Huang HJ, Ross CR, Blecha F: Chemoattractant properties of pr-39, a neutrophil antibacterial peptide. J Leukoc Biol 1997;61:624-629.
57. Ghosh SK, Gupta S, Jiang B, Weinberg A: Fusobacterium nucleatum and human beta defensins modulate the release of antimicrobial chemokine ccl20/mip-3{alpha}. Infect Immun 2011; 79:4578-4587.
58. Montreekachon P, Chotjumlong P, Bolscher JG, Nazmi K, Reutrakul V, Krisanaprakornkit S: Involvement of p2x(7) purinergic receptor and mek1/2 in interleukin-8 upregulation by ll-37 in human gingival fibroblasts. J Periodontal Res 2011;46:327-337.
59. Bowdish DM, Davidson DJ, Hancock RE: Immunomodulatory properties of defensins and cathelicidins. Curr Top Microbiol Immunol 2006;306:27-66.
60. Nagaoka I, Niyonsaba F, Tsutsumi-Ishii Y, Tamura H, Hirata M: Evaluation of the effect of human beta-defensins on neutrophil apoptosis. Int Immunol 2008;20:543-553.
61. Niyonsaba F, Ushio H, Hara M, Yokoi H, Tominaga M, Takamori K, Kajiwara N, Saito H, Nagaoka I, Ogawa H, Okumura K: Antimicrobial peptides human beta-defensins and cathelicidin ll-37 induce the secretion of a pruritogenic cytokine il-31 by human mast cells. J Immunol 2010;184:3526-3534.
62. Bowdish DM, Davidson DJ, Speert DP, Hancock RE: The human cationic peptide ll-37 induces activation of the extracellular signal- regulated kinase and p38 kinase pathways in primary human monocytes. J Immunol 2004;172:3758-3765.
63. Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sorensen OE, Borregaard N, Rabe KF, Hiemstra PS: The antimicrobial peptide ll-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 2003;171:6690-6696.
64. Soehnlein O, Kai-Larsen Y, Frithiof R, Sorensen OE, Kenne E, Scharffetter-Kochanek K, Eriksson EE, Herwald H, Agerberth B, Lindbom L: Neutrophil primary granule proteins hbp and hnp1-3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest 2008;118:3491-3502.
65. Soehnlein O, Wantha S, Simsekyilmaz S, Doring Y, Megens RT, Mause SF, Drechsler M, Smeets R, Weinandy S, Schreiber F, Gries T, Jockenhoevel S, Moller M, Vijayan S, van Zandvoort MA, Agerberth B, Pham CT, Gallo RL, Hackeng TM, Liehn EA, Zernecke A, Klee D, Weber C: Neutrophil-derived cathelicidin protects from neointimal hyperplasia. Sci Transl Med 2011;3:103ra198.
66. Steinstraesser L, Koehler T, Jacobsen F, Daigeler A, Goertz O, Langer S, Kesting M, Steinau H, Eriksson E, Hirsch T: Host defense peptides in wound healing. Mol Med 2008; 14:528-537.
67. 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: An angiogenic role for the human peptide antibiotic ll-37/hcap-18. J Clin Invest 2003;111:1665-1672.
68. Li J, Post M, Volk R, Gao Y, Li M, Metais C, Sato K, Tsai J, Aird W, Rosenberg RD, Hampton TG, Sellke F, Carmeliet P, Simons M: Pr39, a peptide regulator of angiogenesis. Nat Med 2000;6:49-55.
69. Niyonsaba F, Someya A, Hirata M, Ogawa H, Nagaoka I: 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 2001;31:1066-1075.
70. van der Merwe J, Prysliak T, Gerdts V, Perez- Casal J: Protein chimeras containing the mycoplasma bovis gapdh protein and bovine host-defence peptides retain the properties of the individual components. Microb Pathog 2011;50:269-277.
71. Cao D, Li H, Jiang Z, Cheng Q, Yang Z, Xu C, Cao G, Zhang L: Cpg oligodeoxynucleotide synergizes innate defense regulator peptide for enhancing the systemic and mucosal immune responses to pseudorabies attenuated virus vaccine in piglets in vivo. Int Immunopharmacol 2011;11:748-754.
72. Scruten E, Kovacs-Nolan J, Griebel PJ, Latimer L, Kindrachuk J, Potter A, Babiuk LA, Littel-van den Hurk SD, Napper S: Retro- inversion enhances the adjuvant and cpg co-adjuvant activity of host defence peptide bac2a. Vaccine 2010;28:2945-2956.
73. Torossian A, Gurschi E, Bals R, Vassiliou T, Wulf HF, Bauhofer A: Effects of the antimicrobial peptide ll-37 and hyperthermic preconditioning in septic rats. Anesthesiology 2007; 107:437-441.
74. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, Tangpricha V: Alterations in vitamin d status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med 2009; 7:28.
75. Mandic Havelka A, Yektaei-Karin E, Hultenby K, Sorensen OE, Lundahl J, Berggren V, Marchini G: Maternal plasma level of antimicrobial peptide ll37 is a major determinant factor of neonatal plasma ll37 level. Acta Paediatr 2010;99:836-841.
76. Starner TD, Agerberth B, Gudmundsson GH, McCray PB, Jr.: Expression and activity of beta-defensins and ll-37 in the developing human lung. J Immunol 2005;174:1608-1615.
77. Dale BA, Tao R, Kimball JR, Jurevic RJ: Oral antimicrobial peptides and biological control of caries. BMC Oral Health 2006;6Suppl 1):S13.
78. Mukae H, Iiboshi H, Nakazato M, Hiratsuka T, Tokojima M, Abe K, Ashitani J, Kadota J, Matsukura S, Kohno S: Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis. Thorax 2002;57:623-628.
79. Kindrachuk J, Jenssen H, Elliott M, Townsend R, Nijnik A, Lee SF, Gerdts V, Babiuk LA, Halperin SA, Hancock RE: A novel vaccine adjuvant comprised of a synthetic innate defence regulator peptide and cpg oligonucleotide links innate and adaptive immunity. Vaccine 2009;27:4662-4671.
80. Wehkamp J, Schmid M, Stange EF: Defensins and other antimicrobial peptides in inflammatory bowel disease. Curr Opin Gastroenterol 2007;23:370-378.
81. Paulsen F, Pufe T, Conradi L, Varoga D, Tsokos M, Papendieck J, Petersen W: Antimicrobial peptides are expressed and produced in healthy and inflamed human synovial membranes. J Pathol 2002;198:369-377.
82. Sun CL, Zhang FZ, Li P, Bi LQ: Ll-37 expression in the skin in systemic lupus erythematosus. Lupus 2011;20:904-911.
83. Beisswenger C, Kandler K, Hess C, Garn H, Felgentreff K, Wegmann M, Renz H, Vogelmeier C, Bals R: Allergic airway inflammation inhibits pulmonary antibacterial host defense. J Immunol 2006;177:1833-1837.
84. Andresen E, Gunther G, Bullwinkel J, Lange C, Heine H: Increased expression of beta-defensin 1defb1) in chronic obstructive pulmonary disease. PLoS One 2011;6:e21898.
85. Anderson RL, Hiemstra PS, Ward C, Forrest IA, Murphy D, Proud D, Lordan J, Corris PA, Fisher AJ: Antimicrobial peptides in lung transplant recipients with bronchiolitis obliterans syndrome. Eur Respir J 2008;32:670-677.
86. Ross DJ, Cole AM, Yoshioka D, Park AK, Belperio JA, Laks H, Strieter RM, Lynch JP, 3rd, Kubak B, Ardehali A, Ganz T: Increased bronchoalveolar lavage human beta-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2004; 78:1222-1224.
87. Rieg S, Steffen H, Seeber S, Humeny A, Kalbacher H, Dietz K, Garbe C, Schittek B: Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol 2005; 174:8003-8010.
88. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY: Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002; 347:1151-1160.
89. Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descargues P, Hovnanian A, Morhenn VB, Gallo RL: Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 2007; 13:975-980.