Skip to main content
SpringerLink
Log in

Antimicrobial Peptides: An Essential Component of the Skin Defensive Barrier

  • Chapter
Antimicrobial Peptides and Human Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 306))

Abstract

The skin is positioned at the interface between an organism’s internal milieu and an external environment characterized by constant assault with potential microbial pathogens. While the skin was formerly considered an inactive physical protective barrier that participates in host immune defense merely by blocking entry of microbial pathogens, it is now apparent that a major role of the skin is to defend the body by rapidly mounting an innate immune response to injury and microbial insult. In the skin, both resident and infiltrating cells synthesize and secrete small peptides that demonstrate broad-spectrum antimicrobial activity against bacteria, fungi, and enveloped viruses. Antimicrobial peptides also act as multifunctional immune effectors by stimulating cytokine and chemokine production, angiogenesis, and wound healing. Cathelicidins and defensins comprise two major families of skin-derived antimicrobial peptides, although numerous others have been described. Many such immune defense molecules are currently being developed therapeutically in an attempt to combat growing bacterial resistance to conventional antibiotics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abachin E, Poyart C, Pellegrini E, Milohanic E, Fiedler F, Berche P, Trieu-Cuot P (2002) Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol Microbiol 43:1–14

    PubMed  CAS  Google Scholar 

  • Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jornvall H, Wigzell H, Gudmundsson GH (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96:3086–3093

    PubMed  CAS  Google Scholar 

  • Ashcroft GS, Lei K, Jin W, Longenecker G, Kulkarni AB, Greenwell-Wild T, Hale-Donze H, McGrady G, Song XY, Wahl SM (2000) Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat Med 6:1147–1153

    PubMed  CAS  Google Scholar 

  • Bals R (2000) Epithelial antimicrobial peptides in host defense against infection. Respir Res 1:141–150

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM (1998) Human betadefensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102:874–880

    PubMed  CAS  Google Scholar 

  • Bals R, Weiner DJ, Moscioni AD, Meegalla RL, Wilson JM (1999) Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect Immun 67:6084–6089

    PubMed  CAS  Google Scholar 

  • Befus AD, Mowat C, Gilchrist M, Hu J, Solomon S, Bateman A (1999) Neutrophil defensins induce histamine secretion from mast cells: mechanisms of action. J Immunol 163:947–953

    PubMed  CAS  Google Scholar 

  • Belaaouaj A, McCarthy R, Baumann M, Gao Z, Ley TJ, Abraham SN, Shapiro SD (1998) Mice lacking neutrophil elastase reveal impaired host defense against Gram-negative bacterial sepsis. Nat Med 4:615–618

    PubMed  CAS  Google Scholar 

  • Belas R, Manos J, Suvanasuthi R (2004) Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides. Infect Immun 72:5159–5167

    PubMed  CAS  Google Scholar 

  • Bick RJ, Poindexter BJ, Bhat S, Gulati S, Buja M, Milner SM (2004) Effects of cytokines and heat shock on defensin levels of cultured keratinocytes. Burns 30:329–333

    PubMed  Google Scholar 

  • Braff MH, Di Nardo A, Gallo RL (2005) Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies. J Invest Dermatol 124:394–400

    PubMed  CAS  Google Scholar 

  • Brogden KA, Ackermann M, McCray PB Jr, Tack BF (2003) Antimicrobial peptides in animals and their role in host defences. Int J Antimicrob Agents 22:465–478

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  • Carretero M, Del Rio M, Garcia M, Escamez MJ, Mirones I, Rivas L, Balague C, Jorcano JL, Larcher F (2004) A cutaneous gene therapy approach to treat infection through keratinocyte-targeted overexpression of antimicrobial peptides. FASEB J 18:1931–1933

    PubMed  CAS  Google Scholar 

  • Chaly YV, Paleolog EM, Kolesnikova TS, Tikhonov II, Petratchenko EV, Voitenok NN (2000) Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw 11:257–266

    PubMed  CAS  Google Scholar 

  • Christophers E, Henseler T (1987) Contrasting disease patterns in psoriasis and atopic dermatitis. Arch Dermatol Res 279[Suppl]:S48–S51

    PubMed  Google Scholar 

  • Chronnell CM, Ghali LR, Ali RS, Quinn AG, Holland DB, Bull JJ, Cunliffe WJ, McKay IA, Philpott MP, Muller-Rover S (2001) Human beta defensin-1 and-2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions. J Invest Dermatol 117:1120–1125

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Cole AM, Shi J, Ceccarelli A, Kim YH, Park A, Ganz T (2001) Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds. Blood 97:297–304

    PubMed  CAS  Google Scholar 

  • Collins LV, Kristian SA, Weidenmaier C, Faigle M, Van Kessel KP, Van Strijp JA, Gotz F, Neumeister B, Peschel A (2002) Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice. J Infect Dis 186:214–219

    PubMed  CAS  Google Scholar 

  • Conner K, Nern K, Rudisill J, O’Grady T, Gallo RL (2002) The antimicrobial peptide LL-37 is expressed by keratinocytes in condyloma acuminatum and verruca vulgaris. J Am Acad Dermatol 47:347–350

    PubMed  Google Scholar 

  • Darmstadt GL, Mentele L, Fleckman P, Rubens CE (1999) Role of keratinocyte injury in adherence of Streptococcus pyogenes. Infect Immun 67:6707–6709

    PubMed  CAS  Google Scholar 

  • De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000) LL-37, the neutrophil granule-and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069–1074

    Google Scholar 

  • Di Nardo A, Vitiello A, Gallo RL (2003) Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol 170:2274–2278

    PubMed  Google Scholar 

  • Dinulos JG, Mentele L, Fredericks LP, Dale BA, Darmstadt GL (2003) Keratinocyte expression of human beta defensin 2 following bacterial infection: role in cutaneous host defense. Clin Diagn Lab Immunol 10:161–166

    PubMed  CAS  Google Scholar 

  • Donnarumma G, Paoletti I, Buommino E, Orlando M, Tufano MA, Baroni A (2004) Malassezia furfur induces the expression of beta-defensin-2 in human keratinocytes in a protein kinase C-dependent manner. Arch Dermatol Res 295:474–481

    PubMed  CAS  Google Scholar 

  • Dorschner RA, Lin KH, Murakami M, Gallo RL (2003) Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response. Pediatr Res 53:566–572

    PubMed  CAS  Google Scholar 

  • Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, Agerberth B, Gudmundsson GH, Gallo RL (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol 117:91–97

    PubMed  CAS  Google Scholar 

  • Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH (2002) Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106:517–525

    PubMed  CAS  Google Scholar 

  • Erdag G, Morgan JR (2002) Interleukin-1alpha and interleukin-6 enhance the antibacterial properties of cultured composite keratinocyte grafts. Ann Surg 235:113–124

    PubMed  Google Scholar 

  • Fang XM, Shu Q, Chen QX, Book M, Sahl HG, Hoeft A, Stuber F (2003) Differential expression of alpha-and beta-defensins in human peripheral blood. Eur J Clin Invest 33:82–87

    PubMed  CAS  Google Scholar 

  • Franzke CW, Baici A, Bartels J, Christophers E, Wiedow O (1996) Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation. J Biol Chem 271:21886–21890

    PubMed  CAS  Google Scholar 

  • Frick IM, Akesson P, Rasmussen M, Schmidtchen A, Bjorck L (2003) SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J Biol Chem 278:16561–16566

    PubMed  CAS  Google Scholar 

  • Frohm M, Agerberth B, Ahangari G, Stahle-Backdahl M, Liden S, Wigzell H, Gudmundsson GH (1997) The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 272:15258–15263

    PubMed  CAS  Google Scholar 

  • Gallo RL, Murakami M, Ohtake T, Zaiou M (2002) Biology and clinical relevance of naturally occurring antimicrobial peptides. J Allergy Clin Immunol 110:823–831

    PubMed  CAS  Google Scholar 

  • Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76:1427–1435

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM (1997) Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88:553–560

    PubMed  CAS  Google Scholar 

  • Gudmundsson GH, Agerberth B (1999) Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system. J Immunol Methods 232:45–54

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Haake A, Scott GA, Holbrook KA (2003) Structure and function of the skin: overview of the epidermis and dermis. In: Freinkel RK, Woodley DT (eds) The biology of the skin. Parthenon, New York, pp 19–45

    Google Scholar 

  • Harder J, Bartels J, Christophers E, Schroder JM (1997) A peptide antibiotic from human skin. Nature 387:861

    PubMed  CAS  Google Scholar 

  • Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707–5713

    PubMed  CAS  Google Scholar 

  • Harwig SS, Ganz T, Lehrer RI (1994) Neutrophil defensins: purification, characterization, and antimicrobial testing. Methods Enzymol 236:160–172

    PubMed  CAS  Google Scholar 

  • Hase K, Eckmann L, Leopard JD, Varki N, Kagnoff MF (2002) Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium. Infect Immun 70:953–963

    PubMed  CAS  Google Scholar 

  • Heilborn JD, Nilsson MF, Kratz G, Weber G, Sorensen O, Borregaard N, Stahle-Backdahl M (2003) The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 120:379–389

    PubMed  CAS  Google Scholar 

  • Henseler T, Christophers E (1995) Disease concomitance in psoriasis. J Am Acad Dermatol 32:982–986

    PubMed  CAS  Google Scholar 

  • Henzler Wildman KA, Lee DK, Ramamoorthy A (2003) Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. Biochemistry 42:6545–6558

    PubMed  CAS  Google Scholar 

  • Hornef MW, Wick MJ, Rhen M, Normark S (2002) Bacterial strategies for overcoming host innate and adaptive immune responses. Nat Immunol 3:1033–1040

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Islam D, Bandholtz L, Nilsson J, Wigzell H, Christensson B, Agerberth B, Gudmundsson G (2001)Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanismwith bacterial DNA as a potential regulator. Nat Med 7:180–185

    PubMed  CAS  Google Scholar 

  • Jones DE, Bevins CL (1993) Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the humanbowel. FEBS Lett 315:187–192

    PubMed  CAS  Google Scholar 

  • Jung HH, Chae SW, Jung SK, Kim ST, Lee HM, Hwang SJ (2003) Expression of a cathelicidin antimicrobial peptide is augmented in cholesteatoma. Laryngoscope 113:432–435

    PubMed  CAS  Google Scholar 

  • Kamysz W, Okroj M (2003) Novel properties of antimicrobial peptides. Acta Biochim Pol 50:461–469

    PubMed  CAS  Google Scholar 

  • Kao CY, Chen Y, Zhao YH, Wu R (2003) ORFeome-based search of airway epithelial cell-specific novel human [beta]-defensin genes. Am J Respir Cell Mol Biol 29:71–80

    PubMed  CAS  Google Scholar 

  • Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, Issbrucker K, Unterberger P, Zaiou M, Lebherz C, Karl A, Raake P, Pfosser A, Boekstegers P, Welsch U, Hiemstra PS, Vogelmeier C, Gallo RL, Clauss M, Bals R (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665–1672

    PubMed  CAS  Google Scholar 

  • Kristian SA, Durr M, Van Strijp JA, Neumeister B, Peschel A (2003) MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads toprotectionagainst oxygen-independent neutrophil killing. Infect Immun 71:546–549

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lehrer RI, Ganz T (1999) Antimicrobial peptides in mammalian and insect host defence. Curr Opin Immunol 11:23–27

    PubMed  CAS  Google Scholar 

  • Lehrer RI, Ganz T (2002) Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 9:18–22

    PubMed  Google Scholar 

  • Lehrer RI, Daher K, Ganz T, Selsted ME (1985) Direct inactivation of viruses by MCP-1 and MCP-2, natural peptide antibiotics fromrabbit leukocytes. J Virol 54:467–472

    PubMed  CAS  Google Scholar 

  • Leung DY (2003) Infection in atopic dermatitis. Curr Opin Pediatr 15:399–404

    PubMed  Google Scholar 

  • Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Invest 113:651–657

    PubMed  CAS  Google Scholar 

  • Liu AY, Destoumieux D, Wong AV, Park CH, Valore EV, Liu L, Ganz T (2002) Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 118:275–281

    PubMed  CAS  Google Scholar 

  • Liu L, Roberts AA, Ganz T (2003) By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide. J Immunol 170:575–580

    PubMed  CAS  Google Scholar 

  • Marchini G, Lindow S, Brismar H, Stabi B, Berggren V, Ulfgren AK, Lonne-Rahm S, Agerberth B, Gudmundsson GH (2002) The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol 147:1127–1134

    PubMed  CAS  Google Scholar 

  • McCray PB Jr, Bentley L (1997) Human airway epithelia express a beta-defensin. Am J Respir Cell Mol Biol 16:343–349

    PubMed  CAS  Google Scholar 

  • Midorikawa K, Ouhara K, Komatsuzawa H, Kawai T, Yamada S, Fujiwara T, Yamazaki K, Sayama K, Taubman MA, Kurihara H, Hashimoto K, Sugai M (2003) Staphylococcus aureus susceptibility to innate antimicrobial peptides, beta-defensins and CAP18, expressed by human keratinocytes. Infect Immun 71:3730–3739

    PubMed  CAS  Google Scholar 

  • Milner SM, Cole A, Ortega MR, Bakir MH, Gulati S, Bhat S, Ganz T (2003) Inducibility of HBD-2 in acute burns and chronic conditions of the lung. Burns 29:553–555

    PubMed  CAS  Google Scholar 

  • Morrison G, Kilanowski F, Davidson D, Dorin J (2002) Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect Immun 70:3053–3060

    PubMed  CAS  Google Scholar 

  • Moser C, Weiner DJ, Lysenko E, Bals R, Weiser JN, Wilson JM (2002) Beta-defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 70:3068–3072

    PubMed  CAS  Google Scholar 

  • Murakami M, Ohtake T, Dorschner RA, Schittek B, Garbe C, Gallo RL (2002) Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. J Invest Dermatol 119:1090–1095

    PubMed  CAS  Google Scholar 

  • Murakami M, Lopez-Garcia B, Braff M, Dorschner RA, Gallo RL (2004) Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol 172:3070–3077

    PubMed  CAS  Google Scholar 

  • Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, Tanaka S, Heumann D (2002) Augmentation of the lipopolysaccharide-neutralizing activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by replacement with hydrophobic and cationic amino acid residues. Clin Diagn Lab Immunol 9:972–982

    PubMed  CAS  Google Scholar 

  • Nickoloff BJ (1999) The immunologic and genetic basis of psoriasis. Arch Dermatol 135:1104–1110

    PubMed  CAS  Google Scholar 

  • Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I (2002) A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106:20–26

    PubMed  CAS  Google Scholar 

  • Niyonsaba F, Hirata M, Ogawa H, Nagaoka I (2003) Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells. Curr Drug Targets Inflamm Allergy 2:224–231

    PubMed  CAS  Google Scholar 

  • Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL (2001) Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414:454–457

    PubMed  CAS  Google Scholar 

  • Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 171:3262–3269

    PubMed  CAS  Google Scholar 

  • Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 347:1151–1160

    PubMed  CAS  Google Scholar 

  • Oono T, Huh WK, Shirafuji Y, Akiyama H, Iwatsuki K (2003) Localization of human beta-defensin-2 and human neutrophil peptides in superficial folliculitis. Br J Dermatol 148:188–191

    PubMed  CAS  Google Scholar 

  • Oren A, Ganz T, Liu L, Meerloo T (2003) In human epidermis, beta-defensin 2 is packaged in lamellar bodies. Exp Mol Pathol 74:180–182

    PubMed  CAS  Google Scholar 

  • Ortega MR, Ganz T, Milner SM (2000) Human beta defensin is absent in burn blister fluid. Burns 26:724–726

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, Kalbacher H, Nieuwenhuizen WF, Jung G, Tarkowski A, van Kessel KP, van Strijp JA (2001) Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J Exp Med 193:1067–1076

    PubMed  CAS  Google Scholar 

  • Philpott MP (2003) Defensins and acne. Mol Immunol 40:457–462

    PubMed  CAS  Google Scholar 

  • Poyart C, Pellegrini E, Marceau M, Baptista M, Jaubert F, Lamy MC, Trieu-Cuot P (2003) Attenuated virulence of Streptococcus agalactiae deficient in D-alanyllipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. Mol Microbiol 49:1615–1625

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC (1998) Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 152:1247–1258

    PubMed  CAS  Google Scholar 

  • Ramanathan B, Davis EG, Ross CR, Blecha F (2002) Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes Infect 4:361–372

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Risso A (2000) Leukocyte antimicrobial peptides: multifunctional effector molecules of innate immunity. J Leukoc Biol 68:785–792

    PubMed  CAS  Google Scholar 

  • Rosenberger CM, Gallo RL, Finlay BB (2004) Interplay between antibacterial effectors: amacrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci U S A 101:2422–2427

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Schmidtchen A, Frick IM, Andersson E, Tapper H, Bjorck L (2002) Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 46:157–168

    PubMed  CAS  Google Scholar 

  • Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, Casavant TL, Mc-Cray PB Jr (2002) Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A 99:2129–2133

    PubMed  CAS  Google Scholar 

  • Scott MG, Gold MR, Hancock RE (1999) Interaction of cationic peptides with lipoteichoic acid and Gram-positive bacteria. Infect Immun 67:6445–6453

    PubMed  CAS  Google Scholar 

  • Selsted ME, Miller SI, Henschen AH, Ouellette AJ (1992) Enteric defensins: antibiotic peptide components of intestinal host defense. J Cell Biol 118:929–936

    PubMed  CAS  Google Scholar 

  • Seo SJ, Ahn SW, Hong CK, Ro BI (2001) Expressions of beta-defensins in human keratinocyte cell lines. J Dermatol Sci 27:183–191

    PubMed  CAS  Google Scholar 

  • Shi J, Ganz T (1998) The role of protegrins and other elastase-activated polypeptides in the bactericidal properties of porcine inflammatory fluids. Infect Immun 66:3611–3617

    PubMed  CAS  Google Scholar 

  • Singh PK, Tack BF, McCray PB Jr, Welsh MJ (2000) Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol 279:L799–L805

    PubMed  CAS  Google Scholar 

  • Sorensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N (2001) Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97:3951–3959

    PubMed  CAS  Google Scholar 

  • Sorensen O, Arnljots K, Cowland JB, Bainton DF, Borregaard N (1997) The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood 90:2796–2803

    PubMed  CAS  Google Scholar 

  • Sorensen OE, Cowland JB, Theilgaard-Monch K, Liu L, Ganz T, Borregaard N (2003) Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J Immunol 170:5583–5589

    PubMed  CAS  Google Scholar 

  • Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O’Neill S, McElvaney NG (2003) Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol 171:931–937

    PubMed  CAS  Google Scholar 

  • Travers JB, Norris DA, Leung DY (2001) The keratinocyte as a target for staphylococcal bacterial toxins. J Investig Dermatol Symp Proc 6:225–230

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Uehara N, Yagihashi A, Kondoh K, Tsuji N, Fujita T, Hamada H, Watanabe N (2003) Humanbeta-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexpression. J Med Microbiol 52:41–45

    PubMed  CAS  Google Scholar 

  • Ulvatne H (2003) Antimicrobial peptides: potential use in skin infections. Am J Clin Dermatol 4:591–595

    PubMed  Google Scholar 

  • Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T (1998) Human betadefensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633–1642

    PubMed  CAS  Google Scholar 

  • Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JH, Mader S, White JH (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173:2909–2912

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC (1999) Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113–117

    PubMed  CAS  Google Scholar 

  • Yang D, Chen Q, Le Y, Wang JM, Oppenheim JJ (2001) Differential regulation of formyl peptide receptor-like 1 expression during the differentiation of monocytes to dendritic cells and macrophages. J Immunol 166:4092–4098

    PubMed  CAS  Google Scholar 

  • Zaiou M, Gallo RL (2002) Cathelicidins, essential gene-encoded mammalian antibiotics. J Mol Med 80:549–561

    PubMed  CAS  Google Scholar 

  • Zaiou M, Nizet V, Gallo RL (2003) Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence. J Invest Dermatol 120:810–816

    PubMed  CAS  Google Scholar 

  • Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 75:39–48

    PubMed  Google Scholar 

  • Zanetti M, Gennaro R, Scocchi M, Skerlavaj B (2000) Structure and biology of cathelicidins. Adv Exp Med Biol 479:203–218

    PubMed  CAS  Google Scholar 

  • Zasloff M (2002) Antimicrobial peptides in health and disease. NEngl JMed 347:1199–1200

    Google Scholar 

  • Zhao C, Wang I, Lehrer RI (1996) Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 396:319–322

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of California, San Diego, Mail Code 111B, San Diego, CA, 92161, USA

    M. H. Braff & R. L. Gallo

Authors
  1. M. H. Braff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. L. Gallo
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Microbiology and Immunology, 3001 Rollins Research Center, Emory University School of Medicine, Atlanta, GA, 30322, USA

    William M. Shafer Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Braff, M.H., Gallo, R.L. (2006). Antimicrobial Peptides: An Essential Component of the Skin Defensive Barrier. In: Shafer, W.M. (eds) Antimicrobial Peptides and Human Disease. Current Topics in Microbiology and Immunology, vol 306. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-29916-5_4

Download citation

Publish with us

Policies and ethics

Search

Navigation