Review: Human antimicrobial proteins — effectors of innate immunity

Abstract

We live in a world populated by an enormous number of micro-organisms. This necessitates the existence of highly effective mechanisms to control microbial growth. Through many research efforts, a chemical defense system based on the production of antimicrobial proteins (AMPs) has been identified. AMPs are endogenous, small proteins exhibiting antimicrobial activity against a wide variety of micro-organisms. The wide distribution of these molecules in the plant and animal kingdom reflects their biological significance. Various human AMPs show a potent effect on pathogenic micro-organisms including antibiotic-resistant bacteria. Thus, there is great interest in understanding the role of AMPs within innate immunity and evaluating their use and/or specific induction to fend off infections. In this review, we provide an overview of the characteristics of human AMPs and discuss examples where AMPs may be involved in the pathogenesis of infectious and inflammatory diseases.

Keywords

Antimicrobial proteins antimicrobial peptides innate immunity host defense infectious diseases

References

Boman HG Antibacterial peptides: basic facts and emerging concepts. J Intern Med 2003; 254: 197—215.

Oppenheim JJ , Yang D. Alarmins: chemotactic activators of immune responses. Curr Opin Immunol 2005; 17: 359—365.

Selsted ME , Harwig SS , Ganz T. , Schilling JW , Lehrer RI Primary structures of three human neutrophil defensins. J Clin Invest 1985; 76: 1436—1439.

Ganz T. , Selsted ME , Szklarek D. et al. Defensins. Natural peptide antibiotics of human neutrophils . J Clin Invest 1985; 76: 1427—1435.

Martin E. , Ganz T. , Lehrer RI Defensins and other endogenous peptide antibiotics of vertebrates . J Leukoc Biol 1995; 58: 128—136.

Chang TL , Vargas Jr J. , DelPortillo A. , Klotman ME Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 2005; 115: 765—773.

Daher KA , Selsted ME , Lehrer RI Direct inactivation of viruses by human granulocyte defensins. J Virol 1986; 60: 1068—1074.

Mackewicz CE , Yuan J. , Tran P. et al. alpha-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS 2003; 17: F23—F32.

Wang W. , Owen SM , Rudolph DL et al. Activity of alpha- and theta-defensins against primary isolates of HIV-1. J Immunol 2004; 173: 515—520.

10.

Kim C. , Gajendran N. , Mittrucker HW et al. Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc Natl Acad Sci USA 2005; 102: 4830—4835.

11.

Yang D. , Biragyn A. , Kwak LW , Oppenheim JJ Mammalian defensins in immunity: more than just microbicidal. Trends Immunol 2002; 23: 291—296.

12.

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.

13.

Territo MC , Ganz T. , Selsted ME , Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils . J Clin Invest 1989; 84: 2017—2020.

14.

Chertov O. , Michiel DF , Xu L. et al. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 1996; 271: 2935—2940.

15.

Oppenheim JJ , Biragyn A. , Kwak LW , Yang D. Roles of antimicrobial peptides such as defensins in innate and adaptive immunity . Ann Rheum Dis 2003; 62 (Suppl 2): ii17—ii21.

16.

Wilde CG , Griffith JE , Marra MN , Snable JL , Scott RW Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family. J Biol Chem 1989; 264: 11200—11203.

17.

Gabay JE , Scott RW , Campanelli D. et al. Antibiotic proteins of human polymorphonuclear leukocytes. Proc Natl Acad Sci USA 1989; 86: 5610—5614.

18.

Ericksen B. , Wu Z. , Lu W. , Lehrer RI Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother 2005; 49: 269—275.

19.

Wu Z. , Cocchi F. , Gentles D. et al. Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett 2005; 579: 162—166.

20.

Bevins CL Paneth cell defensins: key effector molecules of innate immunity. Biochem Soc Trans 2006; 34: 263—266.

21.

Ghosh D. , Porter E. , Shen B. et al. Paneth cell trypsin is the processing enzyme for human defensin-5 . Nat Immunol 2002; 3: 583—590.

22.

Ouellette AJ Paneth cells and innate immunity in the crypt microenvironment. Gastroenterology 1997; 113: 1779—1784.

23.

Salzman NH , Ghosh D. , Huttner KM , Paterson Y. , Bevins CL Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003; 422: 522—526.

24.

Schibli DJ , Hunter HN , Aseyev V. et al. The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus. J Biol Chem 2002; 277: 8279—8289.

25.

Valore EV , Park CH , Quayle AJ , Wiles KR , McCray Jr PB , Ganz T. Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 1998; 101: 1633—1642.

26.

Jia HP , Starner T. , Ackermann M. , Kirby P. , Tack BF , McCray Jr PB Abundant human beta-defensin-1 expression in milk and mammary gland epithelium. J Pediatr 2001; 138: 109—112.

27.

Hiratsuka T. , Nakazato M. , Ihi T. et al. Structural analysis of human beta-defensin-1 and its significance in urinary tract infection. Nephron 2000; 85: 34—40.

28.

Zucht HD , Grabowsky J. , Schrader M. et al. Human beta-defensin-1: a urinary peptide present in variant molecular forms and its putative functional implication. Eur J Med Res 1998; 3: 315—323.

29.

Fulton C. , Anderson GM , Zasloff M. , Bull R. , Quinn AG Expression of natural peptide antibiotics in human skin. Lancet 1997; 350: 1750—1751.

30.

Harder J. , Meyer-Hoffert U. , Wehkamp K. , Schwichtenberg L. , Schröder JM 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.

31.

Singh PK , Jia HP , Wiles K. et al. Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci USA 1998; 95: 14961—14966.

32.

Sahasrabudhe KS , Kimball JR , Morton TH , Weinberg A. , Dale BA Expression of the antimicrobial peptide, human beta-defensin 1, in duct cells of minor salivary glands and detection in saliva . J Dent Res 2000; 79: 1669—1674.

33.

Krisanaprakornkit S. , Weinberg A. , Perez CN , Dale BA Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue . Infect Immun 1998; 66: 4222—4228.

34.

Dunsche A. , Acil Y. , Siebert R. , Harder J. , Schröder JM , Jepsen S. Expression profile of human defensins and antimicrobial proteins in oral tissues . J Oral Pathol Med 2001; 30: 154—158.

35.

Yang D. , Chertov O. , Bykovskaia SN et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525—528.

36.

Donald CD , Sun CQ , Lim SD et al. Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas. Lab Invest 2003; 83: 501—505.

37.

Sun CQ , Arnold R. , Fernandez-Golarz C. et al. Human {beta}defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma. Cancer Res 2006; 66: 8542—8549.

38.

Harder J. , Bartels J. , Christophers E. , Schröder JM A peptide antibiotic from human skin. Nature 1997; 387: 861.

39.

Krisanaprakornkit S. , Kimball JR , Weinberg A. , Darveau RP , Bainbridge BW , Dale BA Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect Immun 2000 ; 68: 2907—2915.

40.

Liu AY , Destoumieux D. , Wong AV et al. Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 2002; 118: 275—281.

41.

Schmid P. , Grenet O. , Medina J. , Chibout SD , Osborne C. , Cox DA An intrinsic antibiotic mechanism in wounds and tissue-engineered skin. J Invest Dermatol 2001; 116: 471—472.

42.

Liu L. , Wang L. , Jia HP et al. Structure and mapping of the human beta-defensin HBD-2 gene and its expression at sites of inflammation. Gene 1998; 222: 237—244.

43.

Wolk K. , Kunz S. , Witte E. , Friedrich M. , Asadullah K. , Sabat R. IL-22 increases the innate immunity of tissues. Immunity 2004; 21: 241—254.

44.

Kao CY , Chen Y. , Thai P. et al. IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol 2004; 173: 3482—3491.

45.

McDermott AM , Redfern RL , Zhang B. , Pei Y. , Huang L. , Proske RJ Defensin expression by the cornea: multiple signalling pathways mediate IL-1beta stimulation of hBD-2 expression by human corneal epithelial cells. Invest Ophthalmol Vis Sci 2003; 44: 1859—1865.

46.

O'Neil DA , Cole SP , Martin-Porter E. et al. Regulation of human beta-defensins by gastric epithelial cells in response to infection with Helicobacter pylori or stimulation with interleukin-1 . Infect Immun 2000; 68: 5412—5415.

47.

Ogushi K. , Wada A. , Niidome T. et al. Salmonella enteritidis FliC (flagella filament protein) induces human beta-defensin-2 mRNA production by Caco-2 cells. J Biol Chem 2001; 276: 30521—30526.

48.

Tsutsumi-Ishii Y. , Nagaoka I. NF-kappa B-mediated transcriptional regulation of human beta-defensin-2 gene following lipopolysaccharide stimulation . J Leukoc Biol 2002; 71: 154—162.

49.

Voss E. , Wehkamp J. , Wehkamp K. , Stange EF , Schröder JM , Harder J. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2 . J Biol Chem 2006; 281: 2005—2011.

50.

Wada A. , Ogushi K. , Kimura T. et al. Helicobacter pylori-mediated transcriptional regulation of the human beta-defensin 2 gene requires NF-kappaB. Cell Microbiol 2001; 3: 115—123.

51.

Wehkamp J. , Harder J. , Wehkamp K. et al. NF-kappaB- and AP-1mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun 2004 ; 72: 5750—5758.

52.

Wehkamp K. , Schwichtenberg L. , Schröder JM , Harder J. Pseudomonas aeruginosa- and IL-1beta-mediated induction of human beta-defensin-2 in keratinocytes is controlled by NF-kappaB and AP-1. J Invest Dermatol 2006; 126: 121—127.

53.

Chung WO , Dale BA Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species. Infect Immun 2004; 72: 352—358.

54.

Varoga D. , Pufe T. , Harder J. et al. Production of endogenous antibiotics in articular cartilage . Arthritis Rheum 2004; 50: 3526—3534.

55.

Bals R. , Wang X. , Wu Z. et al. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 1998 ; 102: 874—880.

56.

Harder J. , Meyer-Hoffert U. , Teran LM et al. Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. Am J Respir Cell Mol Biol 2000; 22: 714—721.

57.

Tomita T. , Hitomi S. , Nagase T. et al. Effect of ions on antibacterial activity of human beta defensin 2. Microbiol Immunol 2000; 44: 749—754.

58.

Baird RM , Brown H. , Smith AW , Watson ML Burkholderia cepacia is resistant to the antimicrobial activity of airway epithelial cells. Immunopharmacology 1999; 44: 267—272.

59.

Brissette CA , Lukehart SA Treponema denticola is resistant to human beta-defensins. Infect Immun 2002 ; 70: 3982—3984.

60.

Fernie-King BA , Seilly DJ , Lachmann PJ The interaction of streptococcal inhibitor of complement (SIC) and its proteolytic fragments with the human beta defensins . Immunology 2004; 111: 444—452.

61.

Huang GT , Zhang HB , Kim D. , Liu L. , Ganz T. A model for antimicrobial gene therapy: demonstration of human beta-defensin 2 antimicrobial activities in vivo. Hum Gene Ther 2002; 13: 2017—2025.

62.

Rice WG , Ganz T. , Kinkade Jr JM , Selsted ME , Lehrer RI , Parmley RT Defensin-rich dense granules of human neutrophils. Blood 1987; 70: 757—765.

63.

Proud D. , Sanders SP , 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.

64.

Quinones-Mateu ME , Lederman MM , Feng Z. et al. Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS 2003; 17: F39—F48.

65.

Niyonsaba F. , Ogawa H. , Nagaoka I. Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology 2004; 111: 273—281.

66.

Niyonsaba F. , Iwabuchi K. , Matsuda H. , Ogawa H. , Nagaoka I. Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol 2002; 14: 421—426.

67.

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.

68.

Harder J. , Bartels J. , Christophers E. , Schröder JM Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 2001; 276: 5707—5713.

69.

Garcia JR , Jaumann F. , Schulz S. et al. Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction . Cell Tissue Res 2001; 306: 257—264.

70.

Jia HP , Schutte BC , Schudy A. et al. Discovery of new human beta-defensins using a genomics-based approach. Gene 2001; 263: 211—218.

71.

Menzies BE , Kenoyer A. Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human beta-defensin 3 in skin keratinocytes. Infect Immun 2006; 74: 6847—6854.

72.

Nomura I. , Goleva E. , Howell MD et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 2003; 171: 3262—3269.

73.

Sorensen OE , Thapa DR , Roupe KM et al. Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor . J Clin Invest 2006 ; 116: 1878—1885.

74.

Sorensen OE , Thapa DR , Rosenthal A. , Liu L. , Roberts AA , Ganz T. Differential regulation of {beta}-defensin expression in human skin by microbial stimuli. J Immunol 2005; 174: 4870—4879.

75.

Midorikawa K. , Ouhara K. , Komatsuzawa H. et al. Staphylococcus aureus susceptibility to innate antimicrobial peptides, beta-defensins and CAP18, expressed by human keratinocytes. Infect Immun 2003; 71: 3730—3739.

76.

Sahly H. , Schubert S. , Harder J. et al. Burkholderia is highly resistant to human beta-defensin 3. Antimicrob Agents Chemother 2003; 47: 1739—1741.

77.

Hoover DM , Wu Z. , Tucker K. , Lu W. , Lubkowski J. Antimicrobial characterization of human beta-defensin 3 derivatives . Antimicrob Agents Chemother 2003; 47: 2804—2809.

78.

Maisetta G. , Batoni G. , Esin S. et al. Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria. Antimicrob Agents Chemother 2003; 47: 3349—3351.

79.

Hazrati E. , Galen B. , Lu W. et al. Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J Immunol 2006; 177: 8658—8666.

80.

Wu Z. , Hoover DM , Yang D. et al. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc Natl Acad Sci USA 2003; 100: 8880—8885.

81.

Chen X. , Niyonsaba F. , Ushio H. et al. Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability. Eur J Immunol 2007; 37: 434—444.

82.

Garcia JR , Krause A. , Schulz S. et al. Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 2001; 15: 1819—1821.

83.

Yanagi S. , Ashitani J. , Ishimoto H. et al. Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection. Respir Res 2005; 6: 130.

84.

Fahlgren A. , Hammarstrom S. , Danielsson A. , Hammarstrom ML beta-Defensin-3 and -4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis. Clin Exp Immunol 2004 ; 137: 379—385.

85.

Yamaguchi Y. , Nagase T. , Makita R. et al. Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice. J Immunol 2002; 169: 2516—2523.

86.

Yenugu S. , Hamil KG , Radhakrishnan Y. , French FS , Hall SH The androgen-regulated epididymal sperm-binding protein, human beta-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial beta-defensin. Endocrinology 2004; 145: 3165—3173.

87.

Schutte BC , Mitros JP , Bartlett JA et al. Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci USA 2002; 99: 2129—2133.

88.

Dyer KD , Rosenberg HF The RNase a superfamily: generation of diversity and innate host defense . Mol Divers 2006; 10: 585—597.

89.

Sur S. , Glitz DG , Kita H. et al. Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes. J Leukoc Biol 1998; 63: 715—722.

90.

Monteseirin J. , Vega A. , Chacon P. et al. Neutrophils as a novel source of eosinophil cationic protein in IgE-mediated processes. J Immunol 2007; 179: 2634—2641.

91.

Rosenberg HF The eosinophil ribonucleases. Cell Mol Life Sci 1998; 54: 795—803.

92.

Rosenberg HF Recombinant human eosinophil cationic protein. Ribonuclease activity is not essential for cytotoxicity. J Biol Chem 1995 ; 270: 7876—7881.

93.

Domachowske JB , Dyer KD , Adams AG , Leto TL , Rosenberg HF Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with direct antiviral activity. Nucleic Acids Res 1998 ; 26: 3358—3363.

94.

Yang D. , Rosenberg HF , Chen Q. , Dyer KD , Kurosaka K. , Oppenheim JJ Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells. Blood 2003 ; 102: 3396—3403.

95.

Yang D. , Chen Q. , Rosenberg HF et al. Human ribonuclease A superfamily members, eosinophil-derived neurotoxin and pancreatic ribonuclease, induce dendritic cell maturation and activation. J Immunol 2004; 173: 6134—6142.

96.

Domachowske JB , Bonville CA , Dyer KD , Rosenberg HF Evolution of antiviral activity in the ribonuclease A gene superfamily: evidence for a specific interaction between eosinophil-derived neurotoxin (EDN/RNase 2) and respiratory syncytial virus. Nucleic Acids Res 1998; 26: 5327—5332.

97.

Phipps S. , Lam CE , Mahalingam S. et al. Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 2007; 110: 1578—1586.

98.

Fett JW , Strydom DJ , Lobb RR et al. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry 1985 ; 24: 5480—5486.

99.

Loverix S. , Steyaert J. Ribonucleases: from prototypes to therapeutic targets? Curr Med Chem 2003; 10: 779—785.

100.

Matousek J. Ribonucleases and their antitumor activity . Comp Biochem Physiol C Toxicol Pharmacol 2001; 129: 175—191.

101.

Leonidas DD , Shapiro R. , Allen SC , Subbarao GV , Veluraja K. , Acharya KR Refined crystal structures of native human angiogenin and two active site variants: implications for the unique functional properties of an enzyme involved in neovascularisation during tumour growth . J Mol Biol 1999; 285: 1209—1233.

102.

Rybak SM , Fett JW , Yao QZ , Vallee BL Angiogenin mRNA in human tumor and normal cells. Biochem Biophys Res Commun 1987; 146: 1240—1248.

103.

Hooper LV , Stappenbeck TS , Hong CV , Gordon JI Angiogenins: a new class of microbicidal proteins involved in innate immunity . Nat Immunol 2003; 4: 269—273.

104.

Harder J. , Schröder JM RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem 2002; 277: 46779—46784.

105.

Zhang J. , Dyer KD , Rosenberg HF Human RNase 7: a new cationic ribonuclease of the RNase A superfamily . Nucleic Acids Res 2003; 31: 602—607.

106.

Huang YC , Lin YM , Chang TW et al. The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity. J Biol Chem 2007; 282: 4626—4633.

107.

Zhang J. , Dyer KD , Rosenberg HF RNase 8, a novel RNase A superfamily ribonuclease expressed uniquely in placenta . Nucleic Acids Res 2002; 30: 1169—1175.

108.

Rudolph B. , Podschun R. , Sahly H. , Schubert S. , Schröder JM , Harder J. Identification of RNase 8 as a novel human antimicrobial protein. Antimicrob Agents Chemother 2006; 50: 3194—3196.

109.

Heizmann CW , Fritz G. , Schafer BW S100 proteins: structure, functions and pathology . Front Biosci 2002 ; 7: d1356—d1368.

110.

Eckert RL , Broome AM , Ruse M. , Robinson N. , Ryan D. , Lee K. S100 proteins in the epidermis. J Invest Dermatol 2004; 123: 23—33.

111.

Madsen P. , Rasmussen HH , Leffers H. et al. Molecular cloning, occurrence, and expression of a novel partially secreted protein `psoriasin' that is highly up-regulated in psoriatic skin . J Invest Dermatol 1991; 97: 701—712.

112.

Gläser R. , Harder J. , Lange H. , Bartels J. , Christophers E. , Schröder JM Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol 2005; 6: 57—64.

113.

Harder J. , Schröder JM Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins. J Leukoc Biol 2005 ; 77: 476—486.

114.

Li X. , de Leeuw E. , Lu W. Total chemical synthesis of human psoriasin by native chemical ligation . Biochemistry 2005; 44: 14688—14694.

115.

Lee KC , Eckert RL S100A7 (psoriasin) — mechanism of antibacterial action in wounds. J Invest Dermatol 2007; 127: 945—957.

116.

Bevins CL An important clue: fingerprints point to psoriasin in defense against E. coli . Nat Immunol 2005; 6: 12—13.

117.

Clohessy PA , Golden BE Calprotectin-mediated zinc chelation as a biostatic mechanism in host defence. Scand J Immunol 1995; 42: 551—556.

118.

Sohnle PG , Hunter MJ , Hahn B. , Chazin WJ Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14). J Infect Dis 2000; 182: 1272—1275.

119.

Nacken W. , Roth J. , Sorg C. , Kerkhoff C. S100A9/S100A8: myeloid representatives of the S100 protein family as prominent players in innate immunity. Microsc Res Tech 2003; 60: 569—580.

120.

Murthy AR , Lehrer RI , Harwig SS , Miyasaki KT In vitro candidastatic properties of the human neutrophil calprotectin complex . J Immunol 1993; 151: 6291—6301.

121.

Brandtzaeg P. , Gabrielsen TO , Dale I. , Muller F. , Steinbakk M. , Fagerhol MK The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at epithelial surfaces. Adv Exp Med Biol 1995; 371A: 201—206.

122.

Gebhardt C. , Nemeth J. , Angel P. , Hess J. S100A8 and S100A9 in inflammation and cancer . Biochem Pharmacol 2006; 72: 1622—1631.

123.

Cole AM , Kim YH , Tahk S. et al. Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett 2001; 504: 5—10.

124.

Lehrer RI , Ganz T. Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 2002; 9: 18—22.

125.

Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 2004; 75: 39—48.

126.

Agerberth B. , Gunne H. , Odeberg J. , Kogner P. , Boman HG , Gudmundsson GH FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proc Natl Acad Sci USA 1995; 92: 195—199.

127.

Gudmundsson GH , Agerberth B. , Odeberg J. , Bergman T. , Olsson B. , Salcedo R. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur J Biochem 1996 ; 238: 325—332.

128.

Sorensen OE , Follin P. , Johnsen AH et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 2001; 97: 3951—3959.

129.

Nizet V. , Gallo RL Cathelicidins and innate defense against invasive bacterial infection . Scand J Infect Dis 2003; 35: 670—676.

130.

Zanetti M. The role of cathelicidins in the innate host defenses of mammals. Curr Issues Mol Biol 2005; 7: 179—196.

131.

Turner J. , Cho Y. , Dinh NN , Waring AJ , Lehrer RI Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 1998 ; 42: 2206—2214.

132.

Dorschner RA , Lopez-Garcia B. , Peschel A. et al. The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides. FASEB J 2006; 20: 35—42.

133.

Howell MD , Gallo RL , Boguniewicz M. et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 2006; 24: 341—348.

134.

Howell MD , Jones JF , Kisich KO , Streib JE , Gallo RL , Leung DY Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum . J Immunol 2004; 172: 1763—1767.

135.

Gordon YJ , Huang LC , Romanowski EG , Yates KA , Proske RJ , McDermott AM Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity . Curr Eye Res 2005; 30: 385—394.

136.

Schauber J. , Svanholm C. , Termen S. et al. Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways. Gut 2003 ; 52: 735—741.

137.

Raqib R. , Sarker P. , Bergman P. et al. Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc Natl Acad Sci USA 2006; 103: 9178—9183.

138.

Wang TT , Nestel FP , Bourdeau V. et al. 1,25-Dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004; 173: 2909—2912.

139.

Gombart AF , Borregaard N. , Koeffler HP Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 2005; 19: 1067—1077.

140.

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.

141.

De Y. , Chen Q. , Schmidt AP et al. 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 2000; 192: 1069—1074.

142.

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.

143.

Bals R. , Wilson JM Cathelicidins — a family of multifunctional antimicrobial peptides . Cell Mol Life Sci 2003; 60: 711—720.

144.

Nizet V. , Ohtake T. , Lauth X. et al. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 2001; 414: 454—457.

145.

Chromek M. , Slamova Z. , Bergman P. et al. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 2006; 12: 636—641.

146.

Park Y. , Hahm KS Antimicrobial peptides (AMPs): peptide structure and mode of action. J Biochem Mol Biol 2005; 38: 507—516.

147.

Yount NY , Bayer AS , Xiong YQ , Yeaman MR Advances in antimicrobial peptide immunobiology. Biopolymers 2006; 84: 435—458.

148.

Zasloff M. Antimicrobial peptides of multicellular organisms . Nature 2002; 415: 389—395.

149.

Lohner K. , Blondelle SE 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.

150.

Yeaman MR , Yount NY Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 2003; 55: 27—55.

151.

Brogden KA

Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

Nat Rev Microbiol 2005; 3: 238—250.

152.

Wiese A. , Gutsmann T. , Seydel U. Towards antibacterial strategies: studies on the mechanisms of interaction between antibacterial peptides and model membranes. J Endotoxin Res 2003; 9: 67—84.

153.

Kavanagh K. , Dowd S. Histatins: antimicrobial peptides with therapeutic potential. J Pharm Pharmacol 2004; 56: 285—289.

154.

Goetz DH , Holmes MA , Borregaard N. , Bluhm ME , Raymond KN , Strong RK The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 2002; 10: 1033—1043.

155.

Weinberg ED Human lactoferrin: a novel therapeutic with broad spectrum potential. J Pharm Pharmacol 2001; 53: 1303—1310.

156.

Bouma G. , Strober W. The immunological and genetic basis of inflammatory bowel disease . Nat Rev Immunol 2003; 3: 521—533.

157.

Podolsky DK Inflammatory bowel disease. N Engl J Med 2002; 347: 417—429.

158.

Wehkamp J. , Fellermann K. , Herrlinger KR , Bevins CL , Stange EF

Mechanisms of disease: defensins in gastrointestinal diseases. Nat Clin Pract

Gastroenterol Hepatol 2005; 2: 406—415.

159.

Ouellette AJ , Bevins CL Paneth cell defensins and innate immunity of the small bowel. Inflamm Bowel Dis 2001 ; 7: 43—50.

160.

Fahlgren A. , Hammarstrom S. , Danielsson A. , Hammarstrom ML Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis . Clin Exp Immunol 2003; 131: 90—101.

161.

Wehkamp J. , Harder J. , Weichenthal M. et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2003; 9: 215—223.

162.

Hollox EJ , Armour JA , Barber JC Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster. Am J Hum Genet 2003; 73: 591—600.

163.

Aldred PM , Hollox EJ , Armour JA Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3. Hum Mol Genet 2005; 14: 2045—2052.

164.

Fellermann K. , Stange DE , Schaeffeler E. et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 2006; 79: 439—448.

165.

Wehkamp J. , Harder J. , Weichenthal M. et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 2004; 53: 1658—1664.

166.

Wehkamp J. , Salzman NH , Porter E. et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci USA 2005; 102: 18129—18134.

167.

Lala S. , Ogura Y. , Osborne C. et al. Crohn's disease and the NOD2 gene: a role for Paneth cells. Gastroenterology 2003; 125: 47—57.

168.

Ogura Y. , Lala S. , Xin W. et al. Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis. Gut 2003; 52: 1591—1597.

169.

Uehara A. , Fujimoto Y. , Fukase K. , Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines . Mol Immunol 2007; 44: 3100—3111.

170.

Kobayashi KS , Chamaillard M. , Ogura Y. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005; 307: 731—734.

171.

Wehkamp J. , Wang G. , Kubler I. et al. The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J Immunol 2007; 179: 3109—3118.

172.

Schmid M. , Fellermann K. , Fritz P. , Wiedow O. , Stange EF , Wehkamp J. Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn's disease. J Leukoc Biol 2007; 81: 907—915.

173.

Schauber J. , Rieger D. , Weiler F. et al. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol 2006; 18: 615—621.

174.

Nuding S. , Fellermann K. , Wehkamp J. , Stange EF Reduced mucosal antimicrobial activity in Crohn's disease of the colon . Gut 2007; 56: 1240—1247.

175.

Wehkamp J. , Stange EF A new look at Crohn's disease: breakdown of the mucosal antibacterial defense . Ann NY Acad Sci 2006; 1072: 321—331.

176.

Gadsby DC , Vergani P. , Csanady L. The ABC protein turned chloride channel whose failure causes cystic fibrosis . Nature 2006; 440: 477—483.

177.

Soferman R. Immunopathophysiologic mechanisms of cystic fibrosis lung disease. Isr Med Assoc J 2006 ; 8: 44—48.

178.

Smith JJ , Travis SM , Greenberg EP , Welsh MJ Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 1996; 85: 229—236.

179.

Guggino WB Cystic fibrosis salt/fluid controversy: in the thick of it. Nat Med 2001; 7: 888—889.

180.

Boucher RC New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J 2004; 23: 146—158.

181.

Taggart CC , Greene CM , Smith SG et al. Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol 2003; 171: 931—937.

182.

Bals R. , Weiner DJ , Meegalla RL , Wilson JM Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model. J Clin Invest 1999; 103: 1113—1117.

183.

Henseler T. , Christophers E. Disease concomitance in psoriasis . J Am Acad Dermatol 1995; 32: 982—986.

184.

de Jongh GJ , Zeeuwen PL , Kucharekova M. et al. High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J Invest Dermatol 2005; 125: 1163—1173.

185.

Ong PY , Ohtake T. , Brandt C. et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002; 347: 1151—1160.

186.

Howell MD , Novak N. , Bieber T. et al. Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis. J Invest Dermatol 2005 ; 125: 738—745.

187.

Boguniewicz M. , Leung DY Atopic dermatitis. J Allergy Clin Immunol 2006; 117: S475—S480.

188.

Yamasaki K. , Schauber J. , Coda A. et al. Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J 2006; 20: 2068—2080.

189.

Butmarc J. , Yufit T. , Carson P. , Falanga V. Human beta-defensin-2 expression is increased in chronic wounds. Wound Repair Regen 2004 ; 12: 439—443.

190.

Ortega MR , Ganz T. , Milner SM Human beta defensin is absent in burn blister fluid. Burns 2000; 26: 724—726.

191.

Milner SM , Ortega MR Reduced antimicrobial peptide expression in human burn wounds. Burns 1999; 25: 411—413.

192.

Dorschner RA , Pestonjamasp VK , Tamakuwala S. et al. Cutaneous injury induces the release of cathelicidin antimicrobial peptides active against group A Streptococcus . J Invest Dermatol 2001; 117: 91—97.

193.

Heilborn JD , Nilsson MF , Kratz G. et al. The cathelicidin antimicrobial 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.

194.

Jacobsen F. , Mittler D. , Hirsch T. et al. 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.

195.

Sorensen OE , Cowland JB , 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.

196.

Niyonsaba F. , Ushio H. , Nakano N. et al. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 2007; 127: 594—604.

197.

Ganz T. , Metcalf JA , Gallin JI , Boxer LA , Lehrer RI Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak—Higashi syndrome and `specific' granule deficiency . J Clin Invest 1988; 82: 552—556.

198.

Carlsson G. , Fasth A. Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original `Kostmann family' and a review. Acta Paediatr 2001; 90: 757—764.

199.

Putsep K. , Carlsson G. , Boman HG , Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 2002; 360: 1144—1149.

200.

Liu PT , Stenger S. , Li H. et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311: 1770—1773.

201.

Stenger S. , Hanson DA , Teitelbaum R. et al. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 1998 ; 282: 121—125.

202.

Gutsmann T. , Hagge SO , David A. et al. Lipid-mediated resistance of Gram-negative bacteria against various pore-forming antimicrobial peptides. J Endotoxin Res 2005; 11: 167—173.

203.

Ooi CE , Weiss J. , Doerfler ME , Elsbach P. Endotoxin-neutralizing properties of the 25 kD N-terminal fragment and a newly isolated 30 kD C-terminal fragment of the 55—60 kD bactericidal/permeability-increasing protein of human neutrophils . J Exp Med 1991; 174: 649—655.

204.

Marra MN , Wilde CG , Griffith JE , Snable JL , Scott RW Bactericidal/permeability-increasing protein has endotoxin-neutralizing activity . J Immunol 1990; 144: 662—666.

205.

Levy O. , Ooi CE , Elsbach P. , Doerfler ME , Lehrer RI , Weiss J. Antibacterial proteins of granulocytes differ in interaction with endotoxin. Comparison of bactericidal/permeability-increasing protein, p15s, and defensins . J Immunol 1995; 154: 5403—5410.

206.

Elsbach P. The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense. J Leukoc Biol 1998; 64: 14—18.

207.

Iovine NM , Elsbach P. , Weiss J. An opsonic function of the neutrophil bactericidal/permeability-increasing protein depends on both its N- and C-terminal domains. Proc Natl Acad Sci USA 1997; 94: 10973—10978.

208.

Larrick JW , Hirata M. , Balint RF , Lee J. , Zhong J. , Wright SC Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 1995; 63: 1291—1297.

209.

Cirioni O. , Giacometti A. , Ghiselli R. et al. LL-37 protects rats against lethal sepsis caused by Gram-negative bacteria. Antimicrob Agents Chemother 2006; 50: 1672—1679.

210.

Augusto LA , Decottignies P. , Synguelakis M. , Nicaise M. , Le Marechal P. , Chaby R. Histones: a novel class of lipopolysaccharide-binding molecules. Biochemistry 2003; 42: 3929—3938.

211.

Harder J. , Schröder J. Antimicrobial peptides in skin disease. Drug Discovery Today: Therapeutic Strategies 2006; 3: 93—100.

212.

Levin M. , Quint PA , Goldstein B. et al. 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.

213.

Giroir BP , Scannon PJ , Levin M. Bactericidal/permeability-increasing protein — lessons learned from the phase III, randomized, clinical trial of rBPI21 for adjunctive treatment of children with severe meningococcemia. Crit Care Med 2001; 29: S130—S135.

214.

Schultz H. , Weiss JP The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease. Clin Chim Acta 2007 ; 384: 12—23.

215.

Levy O. Therapeutic potential of the bactericidal/permeability-increasing protein . Expert Opin Investig Drugs 2002; 11: 159—167.

216.

Van Dyke T. , Paquette D. , Grossi S. et al. Clinical and microbial evaluation of a histatin-containing mouthrinse in humans with experimental gingivitis: a phase-2 multi-center study. J Clin Periodontol 2002; 29: 168—176.

217.

Peschel A. , Sahl HG The co-evolution of host cationic antimicrobial peptides and microbial resistance . Nat Rev Microbiol 2006; 4: 529—536.

218.

Kovacs M. , Halfmann A. , Fedtke I. et al. A functional dlt operon, encoding proteins required for incorporation of d-alanine in teichoic acids in Gram-positive bacteria, confers resistance to cationic antimicrobial peptides in Streptococcus pneumoniae. J Bacteriol 2006; 188: 5797—5805.

219.

Peschel A. , Otto M. , Jack RW , Kalbacher H. , Jung G. , Gotz F. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 1999; 274: 8405—8410.

220.

Guo L. , Lim KB , Poduje CM et al. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell 1998; 95: 189—198.

221.

Peschel A. , Jack RW , Otto M. et al. 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 2001; 193: 1067—1076.

222.

Zhang H. , Porro G. , Orzech N. , Mullen B. , Liu M. , Slutsky AS Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose-related fashion. Am J Physiol 2001 ; 280: L947—L954.

223.

van den Berg RH , Faber-Krol MC , van Wetering S. , Hiemstra PS , Daha MR Inhibition of activation of the classical pathway of complement by human neutrophil defensins. Blood 1998; 92: 3898—3903.

224.

Groeneveld TW , Ramwadhdoebe TH , Trouw LA et al. Human neutrophil peptide-1 inhibits both the classical and the lectin pathway of complement activation. Mol Immunol 2007; 44: 3608—3614.

225.

Schröder JM , Harder J. Human beta-defensin-2. Int J Biochem Cell Biol 1999; 31: 645—651.

226.

Maisetta G. , Batoni G. , Esin S. et al. In vitro bactericidal activity of human beta-defensin 3 against multidrug-resistant nosocomial strains . Antimicrob Agents Chemother 2006; 50: 806—809.

227.

Durr UH , Sudheendra US , Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides . Biochim Biophys Acta 2006; 1758: 1408—1425.

228.

van der Strate BW , Beljaars L. , Molema G. , Harmsen MC , Meijer DK Antiviral activities of lactoferrin. Antiviral Res 2001; 52: 225—239.

229.

Weiss J. , Elsbach P. , Olsson I. , Odeberg H. Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem 1978; 253: 2664—2672.

230.

Rieg S. , Garbe C. , Sauer B. , Kalbacher H. , Schittek B. Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions. Br J Dermatol 2004; 151: 534—539.

231.

Schittek B. , Hipfel R. , Sauer B. et al. Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol 2001; 2: 1133—1137.

232.

Hiemstra PS , Maassen RJ , Stolk J. , Heinzel-Wieland R. , Steffens GJ , Dijkman JH Antibacterial activity of antileukoprotease. Infect Immun 1996; 64: 4520—4524.

233.

Wiedow O. , Harder J. , Bartels J. , Streit V. , Christophers E. Antileukoprotease in human skin: an antibiotic peptide constitutively produced by keratinocytes. Biochem Biophys Res Commun 1998; 248: 904—909.

234.

Thompson RC , Ohlsson K. Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proc Natl Acad Sci USA 1986; 83: 6692—6696.

235.

Wahl SM , McNeely TB , Janoff EN et al. Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-I. Oral Dis 1997; 3 (Suppl 1): S64—S69.

236.

McNeely TB , Dealy M. , Dripps DJ , Orenstein JM , Eisenberg SP , Wahl SM Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro. J Clin Invest 1995 ; 96: 456—464.

237.

Ganz T. Antimicrobial polypeptides. J Leukoc Biol 2004; 75: 34—38.

238.

Molhuizen HO , Alkemade HA , Zeeuwen PL , de Jongh GJ , Wieringa B. , Schalkwijk J. SKALP/elafin: an elastase inhibitor from cultured human keratinocytes. Purification, cDNA sequence, and evidence for transglutaminase cross-linking. J Biol Chem 1993; 268: 12028—12032.

239.

Wiedow O. , Schröder JM , Gregory H. , Young JA , Christophers E. Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J Biol Chem 1990; 265: 14791—14795.

240.

Wiedow O. , Luademann J. , Utecht B. Elafin is a potent inhibitor of proteinase 3. Biochem Biophys Res Commun 1991; 174: 6—10.

241.

Buckland AG , Wilton DC The antibacterial properties of secreted phospholipase A(2). Biochim Biophys Acta 2000; 1488: 71—82.

242.

Royet J. , Dziarski R. Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences. Nat Rev Microbiol 2007; 5: 264—277.

243.

Lu X. , Wang M. , Qi J. et al. Peptidoglycan recognition proteins are a new class of human bactericidal proteins. J Biol Chem 2006; 281: 5895—5907.

244.

Ganz T. Hepcidin — a peptide hormone at the interface of innate immunity and iron metabolism. Curr Top Microbiol Immunol 2006; 306: 183—198.

245.

Atanasiu V. , Manolescu B. , Stoian I. Hepcidin — central regulator of iron metabolism. Eur J Haematol 2007; 78: 1—10.

246.

Wu H. , Kuzmenko A. , Wan S. et al. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J Clin Invest 2003; 111: 1589—1602.

247.

Kuzmenko AI , Wu H. , McCormack FX Pulmonary collectins selectively permeabilize model bacterial membranes containing rough lipopolysaccharide . Biochemistry 2006; 45: 2679—2685.

248.

Ryan MA , Akinbi HT , Serrano AG et al. Antimicrobial activity of native and synthetic surfactant protein B peptides. J Immunol 2006; 176: 416—425.

249.

Hogenkamp A. , Herias MV , Tooten PC , Veldhuizen EJ , Haagsman HP Effects of surfactant protein D on growth, adhesion and epithelial invasion of intestinal Gram-negative bacteria. Mol Immunol 2007; 44: 3517—3527.

250.

Krensky AM Granulysin: a novel antimicrobial peptide of cytolytic T lymphocytes and natural killer cells. Biochem Pharmacol 2000; 59: 317—320.

251.

Kumar J. , Okada S. , Clayberger C. , Krensky AM Granulysin: a novel antimicrobial. Expert Opin Investig Drugs 2001; 10: 321—329.

252.

Parseghian MH , Luhrs KA Beyond the walls of the nucleus: the role of histones in cellular signaling and innate immunity. Biochem Cell Biol 2006; 84: 589—604.

253.

Kim HS , Cho JH , Park HW , Yoon H. , Kim MS , Kim SC Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol 2002; 168: 2356—2364.

254.

Zudaire E. , Portal-Nunez S. , Cuttitta F. The central role of adrenomedullin in host defense. J Leukoc Biol 2006; 80: 237—244.

255.

Zudaire E. , Martinez A. , Cuttitta F. Adrenomedullin and cancer. Regul Pept 2003 ; 112: 175—183.

256.

Watorek W. Azurocidin — inactive serine proteinase homolog acting as a multifunctional inflammatory mediator. Acta Biochim Pol 2003 ; 50: 743—752.

257.

Shafer WM , Katzif S. , Bowers S. et al. Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens. Curr Pharm Des 2002; 8: 695—702.

258.

Campanelli D. , Detmers PA , Nathan CF , Gabay JE Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties. J Clin Invest 1990; 85: 904—915.

259.

Tang YQ , Yeaman MR , Selsted ME Antimicrobial peptides from human platelets. Infect Immun 2002; 70: 6524—6533.

260.

Yang D. , Chen Q. , Hoover DM et al. Many chemokines including CCL20/MIP-3alpha display antimicrobial activity. J Leukoc Biol 2003; 74: 448—455.

261.

Yenugu S. , Hamil KG , Birse CE , Ruben SM , French FS , Hall SH Antibacterial properties of the sperm-binding proteins and peptides of human epididymis 2 (HE2) family; salt sensitivity, structural dependence and their interaction with outer and cytoplasmic membranes of Escherichia coli. Biochem J 2003; 372: 473—483.

262.

von Horsten HH , Derr P. , Kirchhoff C. Novel antimicrobial peptide of human epididymal duct origin. Biol Reprod 2002; 67: 804—813.

263.

Yenugu S. , Hamil KG , French FS , Hall SH

Antimicrobial actions of the human epididymis 2 (HE2) protein isoforms, HE2alpha, HE2beta1 and HE2beta2. Reprod Biol

Endocrinol 2004; 2: 61.