Host defense peptides as effector molecules of the innate immune response: A sledgehammer for drug resistance?

International Journal of Molecular Sciences

Volumn 10, Issue 9, 2009, Pages 3951-3970

  Steinstraesser, Lars ^a   Kraneburg, Ursula M ^a   Hirsch, Tobias ^a   Kesting, Marco ^b   Steinau, Hans Ulrich ^a   Jacobsen, Frank ^a   Al Benna, Sammy ^a  

^a RUHR UNIVERSITY BOCHUM   (Germany)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

Antimicrobial peptides; Bacterial infection; Host defense peptides; Inflammation; Innate immunity; Sepsis

Indexed keywords

ANTIBIOTIC AGENT; AROMATIC AMIDE; BL 2060; CALIXARENE; CATHELICIDIN; CSA 13; CZEN 002; DEFENSIN; HB 107; HB 50; HLF 1 11; HYDRAZIDE DERIVATIVE; IMX 942; MBI 594AN; MERSACIDIN; MX 226; OPEBACAN; PAC 113; PENICILLIN DERIVATIVE; PEPTIDOMIMETIC AGENT; PEXIGANAN ACETATE; PLECTASIN; POLYPEPTIDE ANTIBIOTIC AGENT; PTX 002; PTX 005; PTX 006; PTX 007; SALICYLAMIDE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; XOMA 629;

ACNE; ALLOGENEIC STEM CELL TRANSPLANTATION; ALLOGENIC BONE MARROW TRANSPLANTATION; ANTIBIOTIC RESISTANCE; ANTIFUNGAL ACTIVITY; ANTIMICROBIAL ACTIVITY; BACTERIAL INFECTION; BACTERICIDAL ACTIVITY; BURN; BURN INFECTION; CANCER CHEMOTHERAPY; CANDIDA; CANDIDIASIS; CATHETER INFECTION; DIABETIC FOOT; FEBRILE NEUTROPENIA; FOOT ULCER; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOMODULATION; IMPETIGO; INFECTION; INFECTION RATE; INFLAMMATION; INNATE IMMUNITY; MENINGOCOCCEMIA; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; NONHUMAN; PEPTIDE ANALYSIS; PNEUMOCOCCAL INFECTION; PROPIONIBACTERIUM ACNES; REVIEW; SEPSIS; SKIN INFECTION; STAPHYLOCOCCUS INFECTION; STREPTOCOCCUS INFECTION; THRUSH; WOUND HEALING; WOUND INFECTION;

ANTIMICROBIAL PEPTIDES; BACTERIAL INFECTION; HOST DEFENSE PEPTIDES; INFLAMMATION; INNATE IMMUNITY; SEPSIS;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTIMICROBIAL CATIONIC PEPTIDES; BACTERIA; BACTERIAL INFECTIONS; DRUG RESISTANCE, BACTERIAL; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNITY, INNATE;

BACTERIA (MICROORGANISMS);

EID: 70350056559     PISSN: None     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms10093951     Document Type: Review

References (135)

1. Davies, J. Origins and evolution of antibiotic resistance. Microbiologia 1996, 12, 9-16.
2. Barber, M.; Rozwadowska-Dowzenko, M. Infection by penicillin-resistant staphylococci. Lancet 1948, 2, 641-644.
3. Benner, E.J.; Kayser, F.H. Growing clinical significance of methcillin-resistant Staphylococcus aureus. Lancet 1968, 2, 741-744.
4. Armstrong, G.L.; Conn, L.A.; Pinner R.W. Trends in infectious disease mortality in the United States during the 20th century. JAMA 1999, 281, 61-66. (Pubitemid 29025101)
5. Surveillance for methicillin-resistant Staphylococcus aureus in Canadian hospitals - a report update from the Canadian Nosocomial Infection Surveillance Program. Can. Commun. Dis. Rep. 2005, 31, 33-40.
6. Goetghebeur, M.; Landry, P.A.; Han, D.; Vicente, C. Methicillin-resistant Staphylococcus aureus: A public health issue with economic consequences. Can. J. Infect. Dis. Med. Microbiol. 2007, 18, 27-34. (Pubitemid 46423235)
7. Clark, N.C.; Weigel, L.M.; Patel, J.B.; Tenover, F.C. Comparison of Tn1546-like elements in vancomycin-resistant Staphylococcus aureus isolates from Michigan and Pennsylvania. Antimicrob. Agents. Chemother. 2005, 49, 470-472.
8. Deans, K.J.; Haley, M.; Natanson, C.; Eichacker, P.Q.; Minneci, P.C. Novel therapies for sepsis: A review. J. Trauma 2005, 58, 867-1784
9. Ziebuhr, W.; Xiao, K.; Coulibaly, B.; Schwarz, R.; Dandekar, T. Pharmacogenomic strategies against resistance development in microbial infections. Pharmacogenomics 2004, 5, 361-379. (Pubitemid 38923651)
10. Wesche-Soldato, D.E.; Swan, R.Z.; Chung, C.S.; Ayala, A. The apoptotic pathway as a therapeutic target in sepsis. Curr. Drug Targets 2007, 8, 493-500. (Pubitemid 46672616)
11. Tossi, A.; Sandri, L.; Giangaspero, A. Amphipathic, alpha-helical antimicrobial peptides. Biopolymers 2000, 55, 4-30.
12. Hancock, R.E.; Scott, M.G. The role of antimicrobial peptides in animal defenses. Proc. Natl. Acad. Sci. USA 2000, 97, 8856-8861.
13. Hancock, R.E. Peptide antibiotics. Lancet 1997, 349, 418-422.
14. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 2002, 415, 389-395.
15. Hancock, R.E. Cationic peptides: Effectors in innate immunity and novel antimicrobials. Lancet Infect. Dis. 2004, 1, 156-164.
16. Steinstraesser, L.; Oezdogan, Y.; Wang, S.C.; Steinau, H.U. Host defense peptides in burns. Burns 2004, 30, 619-627.
17. Brahmachary, M.; Krishnan, S.P.; Koh, J.L.; Khan, A.M.; Seah, S.H.; Tan, T.W.; Brusic, V.; Bajic, V.B. ANTIMIC: A database of antimicrobial sequences. Nucleic Acids Res. 2004, 32, D586-D589.
18. Fjell, C.D.; Hancock, R.E.; Cherkasov, A. AMPer: A database and an automated discovery tool for antimicrobial peptides. Bioinformatics 2007, 23, 1148-1155.
19. Wang, G.; Li, X.; Wang, Z. APD2: The updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res. 2009, 37, D933-D937.
20. Andreu, D.; Rivas, L. Animal antimicrobial peptides: An overview. Biopolymers 1998, 47, 415-433.
21. van't Hof, W.; Veerman, E.C.; Helmerhorst, E.J.; Amerongen, A.V. Antimicrobial peptides: Properties and applicability. Biol. Chem. 2001, 382, 597-619.
22. Koczulla, A.R.; Bals, R. Antimicrobial peptides: Current status and therapeutic potential. Drugs 2003, 63, 389-406. (Pubitemid 36259526)
23. Mookherjee, N.; Brown, K.L.; Bowdish, D.M.; Doria, S.; Falsafi, R.; Hokamp, K.; Roche, F.M.; Mu, R.; Doho, G.H.; Pistolic, J.; Powers, J.P.; Bryan, J.; Brinkman, F.S.; Hancock, R.E. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J. Immunol. 2006, 176, 2455-2464.
24. Zanetti, M. The role of cathelicidins in the innate host defenses of mammals. Curr. Issues Mol. Biol. 2005, 7, 179-196. (Pubitemid 41051685)
25. Scott, M.G.; Davidson, D.J.; Gold, M.R.; Bowdish, D.; Hancock, R.E. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J. Immunol. 2002, 169, 3883-3891.
26. 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, P.S.; Vogelmeier, C.; Gallo, R.L.; Clauss, M.; Bals, R. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J. Clin. Invest. 2003, 111, 1665-1672. (Pubitemid 38057748)
27. Jacobsen, F.; Mittler, D.; Hirsch, T.; Gerhards, A.; Lehnhardt, M.; Voss, B.; Steinau, H.U.; Steinstraesser, L. 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. 2005, 12, 1494-1502. (Pubitemid 41508674)
28. Shaykhiev, R.; Beisswenger, C.; Kandler, K.; Senske, J.; Puchner, A.; Damm, T.; Behr, J.; Bals, R. Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. Am. J. Physiol. Lung Cell Mol. Physiol. 2005, 289, L842-L848. (Pubitemid 41504416)
29. Sieprawska-Lupa, M.; Mydel, P.; Krawczyk, K.; Wojcik, K.; Puklo, M.; Lupa, B.; Suder, P.; Silberring, J.; Reed, M.; Pohl, J.; Shafer, W.; McAleese, F.; Foster, T.; Travis, J.; Potempa, J. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob. Agents Chemother. 2004, 48, 4673-4679. (Pubitemid 39577671)
30. Guina, T.; Yi, E.C.; Wang, H.; Hackett, M.; Miller, S.I. A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides. J. Bacteriol. 2000, 182, 4077-4086.
31. Maemoto, A.; Qu, X.; Rosengren, K.J.; Tanabe, H.; Henschen-Edman, A.; Craik, D.J.; Ouellette, A.J. Functional analysis of the alpha-defensin disulfide array in mouse cryptdin-4. J. Biol. Chem. 2004, 279, 44188-44196.
32. Campopiano, D.J.; Clarke, D.J.; Polfer, N.C.; Barran, P.E.; Langley, R.J.; Govan, J.R.; Maxwell, A.; Dorin, J.R. Structure-activity relationships in defensin dimers: A novel link between betadefensin tertiary structure and antimicrobial activity. J. Biol. Chem. 2004, 279, 48671-48679.
33. Wu, Z.; Hoover, D.M.; Yang, D.; Boulegue, C.; Santamaria, F.; Oppenheim, J.J.; Lubkowski, J.; Lu, W. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc. Natl. Acad. Sci. USA 2003, 100, 8880-8885. (Pubitemid 36899192)
34. Yang, D.; Biragyn, A.; Hoover, D.M.; Lubkowski, J.; Oppenheim, J.J. Beta-defensins: Linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999, 286, 525-528.
35. Gabay, J.E.; Scott, R.W.; Campanelli, D.; Griffith, J.; Wilde, C.; Marra, M.N.; Seeger, M.; Nathan, C.F. Antibiotic proteins of human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci. USA 1989, 86, 5610-5614. (Pubitemid 19185594)
36. Lehrer, R.I.; Barton, A.; Daher, K.A.; Harwig, S.S.; Ganz, T.; Selsted, M.E. Interaction of human defensins with Escherichia coli. mechanism of bactericidal activity. J. Clin. Invest. 1989, 84, 553-561. (Pubitemid 19196987)
37. Panyutich, A.V.; Voitenok, N.N.; Lehrer, R.I.; Ganz, T. An enzyme immunoassay for human defensins. J. Immunol. Methods 1991, 141, 149-155.
38. Panyutich, A.V.; Panyutich, E.A.; Krapivin, V.A.; Baturevich, E.A.; Ganz, T. Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis. J. Lab. Clin. Med. 1993, 122, 202-207. (Pubitemid 23239152)
39. Panyutich, A.; Ganz, T. Activated alpha 2-macroglobulin is a principal defensin-binding protein. Am. J. Respir. Cell Mol. Biol. 1991, 5, 101-106.
40. Panyutich, A.V.; Szold, O.; Poon, P.H.; Tseng, Y.; Ganz, T. Identification of defensin binding to C1 complement. FEBS Lett. 1994, 356, 169-173.
41. Tani, K.; Murphy, W.J.; Chertov, O.; Salcedo, R.; Koh, C.Y.; Utsunomiya, I.; Funakoshi, S.; Asai, O.; Herrmann, S.H.; Wang, J.M.; Kwak, L.W.; Oppenheim, J.J. 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.
42. Lemaitre, B.; Nicolas, E.; Michaut, L.; Reichhart, J.M.; Hoffmann, J.A. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996, 86, 973-983.
43. Chromek, M.; Slamova, Z.; Bergman, P.; Kovacs, L.; Podracka, L.; Ehren, I.; Hokfelt, T.; Gudmundsson, G.H.; Gallo, R.L.; Agerberth, B.; Brauner, A. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat. Med. 2006, 12, 636-641. (Pubitemid 43865231)
44. Thompson, L.; Turko, I.; Murad, F. Mass spectrometry-based relative quantification of human neutrophil peptides 1, 2, and 3 from biological samples. Mol. Immunol. 2006, 43, 1485-1489. (Pubitemid 43356389)
45. Zhou, L.; Huang, L.Q.; Beuerman, R.W.; Grigg, M.E.; Li, S.F.; Chew, F.T.; Ang, L.; Stern, M.E.; Tan, D. Proteomic analysis of human tears: Defensin expression after ocular surface surgery. J. Proteome Res. 2004, 3, 410-416. (Pubitemid 39207344)
46. Hegedus, C.M.; Skibola, C.F.; Warner, M.; Skibola, D.R.; Alexander, D.; Lim, S.; Dangleben, N.L.; Zhang, L.; Clark, M.; Pfeiffer, R.M.; Steinmaus, C.; Smith, A.H.; Smith, M.T.; Moore, L.E. Decreased urinary beta-defensin-1 expression as a biomarker of response to arsenic. Toxicol. Sci. 2008, 106, 74-82.
47. Coffelt, S.B.; Waterman, R.S.; Florez, L.; Honer zu Bentrup, K.; Zwezdaryk, K.J.; Tomchuck, S.L.; LaMarca, H.L.; Danka, E.S.; Morris, C.A.; Scandurro, A.B. Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion. Int. J. Cancer 2008, 122, 1030-1039.
48. von Haussen, J.; Koczulla, R.; Shaykhiev, R.; Herr, C.; Pinkenburg, O.; Reimer, D.; Wiewrodt, R.; Biesterfeld, S.; Aigner, A.; Czubayko, F.; Bals, R. The host defence peptide LL-37/hCAP-18 is a growth factor for lung cancer cells. Lung Cancer 2008, 59, 12-23.
49. Bose, S.K.; Gibson, W.; Bullard, R.S.; Donald, C.D. PAX2 oncogene negatively regulates the expression of the host defense peptide human beta defensin-1 in prostate cancer. Mol. Immunol. 2009, 46, 1140-1148.
50. Brown, K.L.; Hancock, R.E. Cationic host defense (antimicrobial) peptides. Curr. Opin. Immunol. 2006, 18, 24-30. (Pubitemid 43049644)
51. Boman, H.G. Peptide antibiotics and their role in innate immunity. Annu. Rev. Immunol. 1995, 13, 61-92.
52. Yang, D.; Biragyn, A.; Kwak, L.W.; Oppenheim, J.J. Mammalian defensins in immunity: More than just microbicidal. Trends Immunol. 2002, 23, 291-296.
53. Bals, R.; Wilson, J.M. Cathelicidins - A family of multifunctional antimicrobial peptides. Cell. Mol. Life Sci. 2003, 60, 711-720. (Pubitemid 36570762)
54. Bowdish, D.M.; Davidson, D.J.; Lau, Y.E.; Lee, K.; Scott, M.G.; Hancock, R.E. Impact of LL-37 on anti-infective immunity. J. Leukoc. Biol. 2005, 77, 451-459.
55. Morrison, G.; Kilanowski, F.; Davidson, D.; Dorin, J. Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect. Immun. 2002, 70, 3053-3060. (Pubitemid 34564166)
56. Niyonsaba, F.; Suzuki, A.; Ushio, H.; Nagaoka, I.; Ogawa, H.; Okumura, K. The human antimicrobial peptide dermcidin activates normal human keratinocytes. Br. J. Dermatol. 2009, 160, 243-249.
57. 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. (Pubitemid 40806311)
58. Bals, R.; Weiner, D.J.; Moscioni, A.D.; Meegalla, R.L.; Wilson, J.M. Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect Immun. 1999, 67, 6084-6089.
59. Salzman, N.H.; Ghosh, D.; Huttner, K.M.; Paterson, Y.; Bevins, C.L. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003, 422, 522-526.
60. Schittek, B.; Paulmann, M.; Senyurek, I.; Steffen, H. The role of antimicrobial peptides in human skin and in skin infectious diseases. Infect. Disord. Drug Targets 2008, 8, 135-143.
61. Harder, J.; Meyer-Hoffert, U.; Wehkamp, K.; Schwichtenberg, L.; Schroder, J.M. Differential gene induction of human beta-defensins (hBD-1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid. J. Invest. Dermatol. 2004, 123, 522-529.
62. Proud, D.; Sanders, S.P.; Wiehler, S. Human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo. J. Immunol. 2004, 172, 4637-4645. (Pubitemid 38375283)
63. Vora, P.; Youdim, A.; Thomas, L.S.; Fukata, M.; Tesfay, S.Y.; Lukasek, K.; Michelsen, K.S.; Wada, A.; Hirayama, T.; Arditi, M.; Abreu, M.T. Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J. Immunol. 2004, 173, 5398-5405. (Pubitemid 39392123)
64. Bhat, S.; Milner, S. Antimicrobial peptides in burns and wounds. Curr. Protein Pept. Sci. 2007, 8, 506-520.
65. Vallender, E.J.; Lahn, B.T. Positive selection on the human genome. Hum. Mol. Genet. 2004, 13, R245-R254.
66. Patil, A.; Hughes, A.L.; Zhang, G. Rapid evolution and diversification of mammalian alphadefensins as revealed by comparative analysis of rodent and primate genes. Physiol. Genomics 2004, 20, 1-11. (Pubitemid 40388499)
67. Andres, E.; Dimarcq, J.L. Cationic antimicrobial peptides: From innate immunity study to drug development. Update. Med. Mal. Infect. 2007, 37, 194-199.
68. Dorschner, R.A.; Lopez-Garcia, B.; Peschel, A.; Kraus, D.; Morikawa, K.; Nizet, V.; Gallo, R.L. The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides. FASEB J. 2006, 20, 35-42.
69. Johansson, J.; Gudmundsson, G.H.; Rottenberg, M.E.; Berndt, K.D.; Agerberth, B. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J. Biol. Chem. 1998, 273, 3718-3724. (Pubitemid 28109800)
70. Oren, Z.; Lerman, J.C.; Gudmundsson, G.H.; Agerberth, B.; Shai, Y. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: Relevance to the molecular basis for its non-cell-selective activity. Biochem. J. 1999, 341, 501-513.
71. Hirsch, T.; Jacobsen, F.; Steinau, H.U.; Steinstraesser, L. Host defense peptides and the new line of defence against multiresistant infections. Protein Pept. Lett. 2008, 15, 238-248.
72. Larrick, J.W.; Hirata, M.; Balint, R.F.; Lee, J.; Zhong, J.; Wright, S.C. Human CAP18: A novel antimicrobial lipopolysaccharide-binding protein. Infect. Immun. 1995, 63, 1291-1297.
73. Steinstraesser, L.; Tippler, B.; Mertens, J.; Lamme, E.; Homann, H.H.; Lehnhardt, M.; Wildner, O.; Steinau, H.U.; Uberla, K. Inhibition of early steps in the lentiviral replication cycle by cathelicidin host defense peptides. Retrovirology 2005, 2, 2-14. (Pubitemid 40617978)
74. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 2002, 415, 389-395.
75. Bowdish, D.M.; Hancock, R.E. Anti-endotoxin properties of cationic host defence peptides and proteins. J. Endotoxin Res. 2005, 11, 230-236.
76. Hancock, R.E.; Rozek, A. Role of membranes in the activities of antimicrobial cationic peptides. FEMS Microbiol. Lett. 2002, 206, 143-149. (Pubitemid 34117610)
77. Hale, J.D.; Hancock, R.E. Alternative mechanisms of action of cationic antimicrobial peptides on bacteria. Expert Rev. Anti. Infect. Ther. 2007, 5, 951-959.
78. Lohner, K.; Blondelle, S.E. Molecular mechanisms of membrane perturbation by antimicrobial peptides and the use of biophysical studies in the design of novel peptide antibiotics. Comb. Chem. High Throughput Screen. 2005, 8, 241-256.
79. Yang, D.; Biragyn, A.; Hoover, D.M.; Lubkowski, J.; Oppenheim, J.J. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu. Rev. Immunol. 2004, 22, 181-215.
80. Finlay, B.B.; Hancock, R.E. Can innate immunity be enhanced to treat microbial infections? Nat. Rev. Microbiol. 2004, 2, 497-504.
81. Hiemstra, P.S.; Fernie-King, B.A.; McMichael, J.; Lachmann, P.J.; Sallenave, J.M. Antimicrobial peptides: Mediators of innate immunity as templates for the development of novel anti-infective and immune therapeutics. Curr. Pharm. Des. 2004, 10, 2891-2905.
82. Selsted, M.E.; Ouellette, A.J. Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 2005, 6, 551-557.
83. Braff, M.H.; Hawkins, M.A.; Di Nardo, A.; Lopez-Garcia, B.; Howell, M.D.; Wong, C.; Lin, K.; Streib, J.E.; Dorschner, R.; Leung, D.Y.; Gallo, R.L. Structure-function relationships among human cathelicidin peptides: Dissociation of antimicrobial properties from host immunostimulatory activities. J. Immunol. 2005, 174, 4271-4278.
84. Davidson, D.J.; Currie, A.J.; Reid, G.S.; Bowdish, D.M.; MacDonald, K.L.; Ma, R.C.; Hancock, R.E.; Speert, D.P. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J. Immunol. 2004, 172, 1146-1156.
85. Nagaoka, I.; Hirota, S.; Niyonsaba, F.; Hirata, M.; Adachi, Y.; Tamura, H.; Heumann, D. Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. J. Immunol. 2001, 167, 3329-3338. (Pubitemid 32852575)
86. Befus, A.D.; Mowat, C.; Gilchrist, M.; Hu, J.; Solomon, S.; Bateman, A. Neutrophil defensins induce histamine secretion from mast cells: Mechanisms of action. J. Immunol. 1999, 163, 947-953. (Pubitemid 29328106)
87. Niyonsaba, F.; Iwabuchi, K.; Someya, A.; Hirata, M.; Matsuda, H.; Ogawa, H.; Nagaoka, I. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 2002, 106, 20-26. (Pubitemid 34437873)
88. Salzet, M. Antimicrobial peptides are signaling molecules. Trends Immunol. 2002, 23, 283-284. (Pubitemid 34628769)
89. Remick, D.G. Pathophysiology of sepsis. Am. J. Pathol. 2007, 170, 1435-1444.
90. Russell, J.A. Management of sepsis. N. Engl. J. Med. 2006, 355, 1699-1713.
91. Calandra, T.; Bochud, P.Y.; Heumann, D. Cytokines in septic shock. Curr. Clin. Top. Infect. Dis. 2002, 22, 1-23.
92. Byl, B.; Clevenbergh, P.; Kentos, A.; Jacobs, F.; Marchant, A.; Vincent, J.L.; Thys, J.P. Ceftazidime- and imipenem-induced endotoxin release during treatment of gram-negative infections. Eur. J. Clin. Microbiol. Infect. Dis. 2001, 20, 804-807.
93. Parker, S.J.; Watkins, P.E. Experimental models of gram-negative sepsis. Br. J. Surg. 2001, 88, 22-30.
94. Shenep, J.L.; Barton, R.P.; Mogan, K.A. Role of antibiotic class in the rate of liberation of endotoxin during therapy for experimental gram-negative bacterial sepsis. J. Infect. Dis. 1985, 151, 1012-1018.
95. Scott, M.G.; Vreugdenhil, A.C.; Buurman, W.A.; Hancock, R.E.; Gold, M.R. Cutting edge: Cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein. J. Immunol. 2000, 164, 549-553.
96. 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.
97. McPhee, J.B.; Hancock, R.E. Function and therapeutic potential of host defence peptides. J. Pept. Sci. 2005, 11, 677-687.
98. Murphy, C.J.; Foster, B.A.; Mannis, M.J.; Selsted, M.E.; Reid, T.W. Defensins are mitogenic for epithelial cells and fibroblasts. J. Cell Physiol. 1993, 155, 408-413. (Pubitemid 23134880)
99. Chavakis, T.; Cines, D.B.; Rhee, J.S.; Liang, O.D.; Schubert, U.; Hammes, H.P.; Higazi, A.A.; Nawroth, P.P.; Preissner, K.T.; Bdeir, K. Regulation of neovascularization by human neutrophil peptides (alpha-defensins): A link between inflammation and angiogenesis. FASEB J. 2004, 18, 1306-1308. (Pubitemid 39561585)
100. Steinstraesser, L.; Ring, A.; Bals, R.; Steinau, H.U.; Langer, S. The human host defense peptide LL37/hCAP accelerates angiogenesis in PEGT/PBT biopolymers. Ann. Plast. Surg. 2006, 56, 93-98. (Pubitemid 43042282)
101. Sorensen, O.E.; Cowland, J.B.; Theilgaard-Monch, K.; Liu, L.; Ganz, T.; Borregaard, N. Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J. Immunol. 2003, 170, 5583-5589. (Pubitemid 36617848)
102. Heilborn, J.D.; Nilsson, M.F.; Kratz, G.; Weber, G.; Sorensen, O.; Borregaard, N.; Stahle- Backdahl, M. 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. 2003, 120, 379-389.
103. Yount, N.Y.; Bayer, A.S.; Xiong, Y.Q.; Yeaman, M.R. Advances in antimicrobial peptide immunobiology. Biopolymers 2006, 84, 435-458.
104. Peschel, A. How do bacteria resist human antimicrobial peptides? Trends Microbiol. 2002, 10, 179-186. (Pubitemid 34242955)
105. Jin, T.; Bokarewa, M.; Foster, T.; Mitchell, J.; Higgins, J.; Tarkowski, A. Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J. Immunol. 2004, 172, 1169-1176. (Pubitemid 38113778)
106. Frick, I.M.; Akesson, P.; Rasmussen, M.; Schmidtchen, A.; Bjorck, L. SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J. Biol. Chem. 2003, 278, 16561-16566.
107. Shafer, W.M.; Qu, X.D.; Waring, A.J.; Lehrer, R.I. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc. Natl. Acad. Sci. USA 1998, 95, 1829-1833.
108. Tzeng, Y.L.; Ambrose, K.D.; Zughaier, S.; Zhou, X.; Miller, Y.K.; Shafer, W.M.; Stephens, D.S. Cationic antimicrobial peptide resistance in Neisseria meningitidis. J. Bacteriol. 2005, 187, 5387-5396.
109. Hancock, R.E.; Sahl, H.G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 2006, 24, 1551-1557. (Pubitemid 44967479)
110. Cox, C.R.; Coburn, P.S.; Gilmore, M.S. Enterococcal cytolysin: A novel two component peptide system that serves as a bacterial defense against eukaryotic and prokaryotic cells. Curr. Protein Pept. Sci. 2005, 6, 77-84.
111. Scott, M.G.; Hancock, R.E. Cationic antimicrobial peptides and their multifunctional role in the immune system. Crit. Rev. Immunol. 2000, 20, 407-431.
112. Ganz, T.; Selsted, M.E.; Lehrer, R.I. Defensins. Eur. J. Haematol. 1990, 44, 1-8.
113. Shai, Y. 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 1999, 1462, 55-70.
114. Matsuzaki, K. Why and how are peptide-lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes. Biochim. Biophys. Acta 1999, 1462, 1-10.
115. Yang, L.; Weiss, T.M.; Lehrer, R.I.; Huang, H.W. Crystallization of antimicrobial pores in membranes: Magainin and protegrin. Biophys. J. 2000, 79, 2002-2009.
116. Dathe, M.; Meyer, J.; Beyermann, M.; Maul, B.; Hoischen, C.; Bienert, M. General aspects of peptide selectivity towards lipid bilayers and cell membranes studied by variation of the structural parameters of amphipathic helical model peptides. Biochim. Biophys. Acta 2002, 1558, 171-186. (Pubitemid 34075532)
117. Fukumoto, K.; Nagaoka, I.; Yamataka, A.; Kobayashi, H.; Yanai, T.; Kato, Y.; Miyano, T. Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats. Pediatr. Surg. Int. 2005, 21, 20-24. (Pubitemid 40169453)
118. Torossian, A.; Gurschi, E.; Bals, R.; Vassiliou, T.; Wulf, H.F.; Bauhofer, A. Effects of the antimicrobial peptide LL-37 and hyperthermic preconditioning in septic rats. Anesthesiology 2007, 107, 437-441. (Pubitemid 47329542)
119. Oren, Z.; Lerman, J.C.; Gudmundsson, G.H.; Agerberth, B.; Shai, Y. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: Relevance to the molecular basis for its non-cell-selective activity. Biochem. J. 1999, 341, 501-513.
120. Ciornei, C.D.; Egesten, A.; Bodelsson, M. Effects of human cathelicidin antimicrobial peptide LL-37 on lipopolysaccharide-induced nitric oxide release from rat aorta in vitro. Acta Anaesthesiol. Scand. 2003, 47, 213-220. (Pubitemid 36349783)
121. 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, 1776-1784. (Pubitemid 41023082)
122. Scott, M.G.; Davidson, D.J.; Gold, M.R.; Bowdish, D.; Hancock, R.E. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J. Immunol. 2002, 169, 3883-3891.
123. 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.
124. Kaus, A.; Jacobsen, F.; Sorkin, M.; Rittig, A.; Voss, B.; Daigeler, A.; Sudhoff, H.; Steinau, H.U.; Steinstraesser, L. Host defence peptides in human burns. Burns 2008, 34, 32-40.
125. Jacobsen, F.; Mohammadi-Tabrisi, A.; Hirsch, T.; Mittler, D.; Mygind, P.H.; Sonksen, C.P.; Raventos, D.; Kristensen, H.H.; Gatermann, S.; Lehnhardt, M.; Daigeler, A.; Steinau, H.U.; Steinstraesser, L. Antimicrobial activity of the recombinant designer host defence peptide Pnovispirin G10 in infected full-thickness wounds of porcine skin. J. Antimicrob. Chemother. 2007, 59, 493-498. (Pubitemid 47073456)
126. Hirsch, T.; von Peter, S.; Dubin, G.; Mittler, D.; Jacobsen, F.; Lehnhardt, M.; Eriksson, E.; Steinau, H.U.; Steinstraesser, L. Adenoviral gene delivery to primary human cutaneous cells and burn wounds. Mol. Med. 2006, 12, 199-207. (Pubitemid 44925018)
127. Steinstraesser, L.; Tack, B.F.; Waring, A.J.; Hong, T.; Boo, L.M.; Fan, M.H.; Remick, D.I.; Su, G.L.; Lehrer, R.I.; Wang, S.C. Activity of novispirin G10 against Pseudomonas aeruginosa in vitro and in infected burns. Antimicrob. Agents. Chemother. 2002, 46, 1837-1844.
128. Sigurdardottir, T.; Andersson, P.; Davoudi, M.; Malmsten, M.; Schmidtchen, A.; Bodelsson, M. In silico identification and biological evaluation of antimicrobial peptides based on human cathelicidin LL-37. Antimicrob. Agents Chemother. 2006, 50, 2983-2989. (Pubitemid 44396402)
129. Eckert, R.; Qi, F.; Yarbrough, D.K.; He, J.; Anderson, M.H.; Shi, W. Adding selectivity to antimicrobial peptides: Rational design of a multidomain peptide against Pseudomonas spp. Antimicrob. Agents Chemother. 2006, 50, 1480-1488.
130. Eckert, R.; Greenberg, E.P.; Qi, F.; Yarbrough, D.K.; He, J.; McHardy, I.; Anderson, M.H.; Shi, W. Enhancement of antimicrobial activity against pseudomonas aeruginosa by coadministration of G10KHc and tobramycin. Antimicrob. Agents Chemother. 2006, 50, 3833-3838. (Pubitemid 44684900)
131. Kristian, S.A.; Timmer, A.M.; Liu, G.Y.; Lauth, X.; Sal-Man, N.; Rosenfeld, Y.; Shai, Y.; Gallo, R.L.; Nizet, V. Impairment of innate immune killing mechanisms by bacteriostatic antibiotics. FASEB J. 2007, 21, 1107-1116. (Pubitemid 46495700)
132. Ghiselli, R.; Giacometti, A.; Cirioni, O.; Mocchegiani, F.; Orlando, F.; D'Amato, G.; Sisti, V.; Scalise, G.; Saba, V. Cecropin B enhances betalactams activities in experimental rat models of gram-negative septic shock. Ann. Surg. 2004, 239, 251-256. (Pubitemid 38176360)
133. Zhang, L.; Falla, T.Y. Antimicrobial peptides: Therapeutic potential. Expert. Opin. Pharmacother. 2006, 7, 653-663.
134. Levin, M.; Quint, P.A.; Goldstein, B.; Barton, P.; Bradley, J.S.; Shemie, S.D.; Yeh, T.; Kim, S.S.; Cafaro, D.P.; Scannon, P.J.; Giroir, B.P. Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: A randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet 2000, 356, 961-967.
135. Hancock, R.E.; Patrzykat, A. Clinical development of cationic antimicrobial peptides: From natural to novel antibiotics. Curr. Drug Targets Infect. Disord. 2002, 2, 79-83. (Pubitemid 34649857)