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Antimicrobial Peptides in Cutaneous Wound Healing

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Book cover Antimicrobial Peptides

Part of the book series: Birkhäuser Advances in Infectious Diseases ((BAID))

Abstract

Injury that breached the physical skin barrier increases the likelihood of infection. The wound healing process is divided into hemostasis, inflammation, proliferation, and tissue remodeling. Antimicrobial peptides play a major role for the antimicrobial defense at all these stages in wound healing, but the main sources of antimicrobial peptides vary with the different stages of wound healing coming from plasma proteins, neutrophils, and keratinocytes. Apart from being part of the antimicrobial defense, antimicrobial peptides play other important roles in wound healing as in angiogenesis, attraction of leukocytes, resolution of inflammation, and proliferation. Future studies will demonstrate whether antimicrobial peptides can be used therapeutically to improve the wound healing processes and reduce scar formation in chronic wounds.

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References

  • Abdillahi SM, Balvanovic S, Baumgarten M, Mörgelin M (2012) Collagen VI encodes antimicrobial activity: novel innate host defense properties of the extracellular matrix. J Innate Immun 4:371–376

    Article  CAS  PubMed  Google Scholar 

  • Abtin A, Eckhart L, Mildner M, Gruber F, Schröder JM, Tschachler E (2008) Flagellin is the principal inducer of the antimicrobial peptide S100A7c (psoriasin) in human epidermal keratinocytes exposed to Escherichia coli. FASEB J 22:2168–2176

    Article  CAS  PubMed  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

    Article  CAS  PubMed  Google Scholar 

  • Betz P, Nerlich A, Wilske J, Tubel J, Penning R, Eisenmenger W (1993) Immunohistochemical localization of collagen types I and VI in human skin wounds. Int J Legal Med 106:31–34

    Article  CAS  PubMed  Google Scholar 

  • Bevins CL, Jones DE, Dutra A, Schaffzin J, Muenke M (1996) Human enteric defensin genes: chromosomal map position and a model for possible evolutionary relationships. Genomics 31:95–106

    Article  CAS  PubMed  Google Scholar 

  • Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ et al (2002) Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298:1025–1029

    Article  CAS  PubMed  Google Scholar 

  • Borregaard N, Cowland JB (1997) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89:3503–3521

    CAS  PubMed  Google Scholar 

  • Borregaard N, Theilgaard-Monch K, Cowland JB, Stahle M, Sørensen OE (2005) Neutrophils and keratinocytes in innate immunity – cooperative actions to provide antimicrobial defense at the right time and place. J Leukoc Biol 77:439–443

    Article  CAS  PubMed  Google Scholar 

  • Borregaard N, Sørensen OE, Theilgaard-Mönch K (2007) Neutrophil granules: a library of innate immunity proteins. Trends Immunol 28:340–345

    Article  CAS  PubMed  Google Scholar 

  • Büchau AS, Hassan M, Kukova G, Lewerenz V, Kellermann S, Würthner JU, Wolf R, Walz M, Gallo RL, Ruzicka T (2007) S100A15, an antimicrobial protein of the skin: regulation by E-coli through toll-like receptor 4. J Invest Dermatol 127:2596–2604

    Article  PubMed  CAS  Google Scholar 

  • Büchau AS, Schauber J, Hultsch T, Stuetz A, Gallo RL (2008) Pimecrolimus enhances TLR2/6-induced expression of antimicrobial peptides in keratinocytes. J Invest Dermatol 128:2646–2654

    Article  PubMed  PubMed Central  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

    Article  PubMed  Google Scholar 

  • Carretero M, Escamez MJ, Garcia M, Duarte B, Holguin A, Retamosa L, Jorcano JL, Rio MD, Larcher F (2008) In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol 128:223–236

    Article  CAS  PubMed  Google Scholar 

  • Chamorro CI, Weber G, Gronberg A, Pivarcsi A, Stahle M (2009) The human antimicrobial peptide LL-37 suppresses apoptosis in keratinocytes. J Invest Dermatol 129:937–944

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Niyonsaba F, Ushio H, Hara M, Yokoi H, Matsumoto K, Saito H, Nagaoka I, Ikeda S, Okumura K et al (2007) Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability. Eur J Immunol 37:434–444

    Article  CAS  PubMed  Google Scholar 

  • Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, Longo DL, Taub DD, Oppenheim JJ (1996) Identification of defensin-1, defensin-2, and CAP37/azurocidin as T- cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 271:2935–2940

    Article  CAS  PubMed  Google Scholar 

  • Chung WO, Hansen SR, Rao D, Dale BA (2004) Protease-activated receptor signaling increases epithelial antimicrobial peptide expression. J Immunol 173:5165–5170

    Article  CAS  PubMed  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

    Article  CAS  PubMed  Google Scholar 

  • Daher KA, Selsted ME, Lehrer RI (1986) Direct inactivation of viruses by human granulocyte defensins. J Virol 60:1068–1074

    CAS  PubMed  PubMed Central  Google Scholar 

  • Davidson JM (1998) Animal models for wound repair. Arch Dermatol Res 290(Suppl):S1–S11

    Article  PubMed  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

    Article  CAS  PubMed  Google Scholar 

  • Dressel S, Harder J, Cordes J, Wittersheim M, Meyer-Hoffert U, Sunderkotter C, Glaser R (2010) Differential expression of antimicrobial peptides in margins of chronic wounds. Exp Dermatol 19:628–632

    Article  CAS  PubMed  Google Scholar 

  • Edgeworth J, Gorman M, Bennett R, Freemont P, Hogg N (1991) Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J Biol Chem 266:7706–7713

    CAS  PubMed  Google Scholar 

  • Edwards R, Harding KG (2004) Bacteria and wound healing. Curr Opin Infect Dis 17:91–96

    Article  PubMed  Google Scholar 

  • Eisenhauer PB, Lehrer RI (1992) Mouse neutrophils lack defensins. Infect Immun 60:3446–3447

    CAS  PubMed  PubMed Central  Google Scholar 

  • Faurschou M, Sørensen OE, Johnsen AH, Askaa J, Borregaard N (2002) Defensin-rich granules of human neutrophils: characterization of secretory properties. Biochim Biophys Acta 1591:29–35

    Article  CAS  PubMed  Google Scholar 

  • Feng Z, Dubyak GR, Lederman MM, Weinberg A (2006) Cutting edge: human beta defensin 3 – a novel antagonist of the HIV-1 coreceptor CXCR4. J Immunol 177:782–786

    Article  CAS  PubMed  Google Scholar 

  • Flannagan RS, Cosio G, Grinstein S (2009) Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nat Rev Microbiol 7:355–366

    Article  CAS  PubMed  Google Scholar 

  • Frick IM, Åkesson P, Herwald H, Mörgelin M, Malmsten M, Nagler DK, Björck L (2006) The contact system – a novel branch of innate immunity generating antibacterial peptides. EMBO J 25:5569–5578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frick IM, Nordin SL, Baumgarten M, Mörgelin M, Sørensen OE, Olin AI, Egesten A (2011) Constitutive and inflammation-dependent antimicrobial peptides produced by epithelium are differentially processed and inactivated by the commensal Finegoldia magna and the pathogen Streptococcus pyogenes. J Immunol 187:4300–4309

    Article  CAS  PubMed  Google Scholar 

  • Ganz T (1987) Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytes. Infect Immun 55:568–571

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ganz T, Selsted ME, Szklarek D, Harwig SSL, Daher K, Bainton DF, Lehrer RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 6:1427–1435

    Article  Google Scholar 

  • Gariboldi S, Palazzo M, Zanobbio L, Selleri S, Sommariva M, Sfondrini L, Cavicchini S, Balsari A, Rumio C (2008) Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of beta-defensin 2 via TLR2 and TLR4. J Immunol 181:2103–2110

    Article  CAS  PubMed  Google Scholar 

  • Gerstel U, Czapp M, Bartels J, Schroder JM (2009) Rhamnolipid-induced shedding of flagellin from Pseudomonas aeruginosa provokes hBD-2 and IL-8 response in human keratinocytes. Cell Microbiol 11:842–853

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Hattori F, Kiatsurayanon C, Okumura K, Ogawa H, Ikeda S, Okamoto K, Niyonsaba F (2014) The antimicrobial protein S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and strengthens the skin’s tight junction barrier. Br J Dermatol 171:742–753

    Article  CAS  PubMed  Google Scholar 

  • Heilborn JD, Nilsson MF, Kratz G, Weber G, Sørensen 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

    Article  CAS  PubMed  Google Scholar 

  • Hessian PA, Edgeworth J, Hogg N (1993) MRP-8 and MRP-14, two abundant Ca(2+)-binding proteins of neutrophils and monocytes. J Leukoc Biol 53:197–204

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hiroshima Y, Hsu K, Tedla N, Chung YM, Chow S, Herbert C, Geczy CL (2014) S100A8 induces IL-10 and protects against acute lung injury. J Immunol 192:2800–2811

    Article  CAS  PubMed  Google Scholar 

  • Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P et al (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901

    Article  CAS  PubMed  Google Scholar 

  • Howell MD, Novak N, Bieber T, Pastore S, Girolomoni G, Boguniewicz M, Streib J, Wong C, Gallo RL, Leung DYM (2005) Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis. J Invest Dermatol 125:738–745

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen F, Mittler D, Hirsch T, Gerhards A, Lehnhardt M, Voss B, Steinau HU, Steinstraesser L (2005) Transient cutaneous adenoviral gene therapy with human host defense peptide hCAP-18/LL-37 is effective for the treatment of burn wound infections. Gene Ther 12:1494–1502

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen LC, Sørensen OE, Cowland JB, Borregaard N, Theilgaard-Mönch K (2008) The secretory leukocyte protease inhibitor (SLPI) and the secondary granule protein lactoferrin are synthesized in myelocytes, colocalize in subcellular fractions of neutrophils, and are coreleased by activated neutrophils. J Leukoc Biol 83:1155–1164

    Article  CAS  PubMed  Google Scholar 

  • Jinquan T, Vorum H, Larsen CG, Madsen P, Rasmussen HH, Gesser B, Etzerodt M, Honore B, Celis JE, Thestrup-Pedersen K (1996) Psoriasin: a novel chemotactic protein. J Invest Dermatol 107:5–10

    Article  CAS  PubMed  Google Scholar 

  • Joiner KA, Ganz T, Albert J, Rostrosen D (1989) The opsonizing ligand on salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes. J Cell Biol 109:2771–2782

    Article  CAS  PubMed  Google Scholar 

  • Koczulla R, Von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, Issbrucker K, Unterberger P, Zaiou M, Lebherz C et al (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lan CC, Wu CS, Huang SM, Kuo HY, Wu IH, Wen CH, Chai CY, Fang AH, Chen GS (2011) High-glucose environment inhibits p38MAPK signaling and reduces human beta-defensin-3 expression in keratinocytes. Mol Med 17:771–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lan CC, Wu CS, Huang SM, Kuo HY, Wu IH, Liang CW, Chen GS (2012) High-glucose environment reduces human beta-defensin-2 expression in human keratinocytes: implications for poor diabetic wound healing. Br J Dermatol 166:1221–1229

    Article  CAS  PubMed  Google Scholar 

  • Lee KC, Eckert RL (2007) S100A7 (Psoriasin) – mechanism of antibacterial action in wounds. J Invest Dermatol 127:945–957

    Article  CAS  PubMed  Google Scholar 

  • Levy O (1996) Antibiotic proteins of polymorphonuclear leukocytes. Eur J Haematol 56:263–277

    Article  CAS  PubMed  Google Scholar 

  • Li J, Post M, Volk R, Gao Y, Li M, Metais C, Sato K, Tsai J, Aird W, Rosenberg RD et al (2000) PR39, a peptide regulator of angiogenesis. Nat Med 6:49–55

    Article  CAS  PubMed  Google Scholar 

  • Li J, Raghunath M, Tan D, Lareu RR, Chen Z, Beuerman RW (2006) Defensins HNP1 and HBD2 stimulation of wound-associated responses in human conjunctival fibroblasts. Invest Ophthalmol Vis Sci 47:3811–3819

    Article  PubMed  Google Scholar 

  • Li D, Lei H, Li Z, Li H, Wang Y, Lai Y (2013) A novel lipopeptide from skin commensal activates TLR2/CD36-p38 MAPK signaling to increase antibacterial defense against bacterial infection. PLoS One 8:e58288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203:2271–2279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim SY, Raftery M, Cai H, Hsu K, Yan WX, Hseih HL, Watts RN, Richardson D, Thomas S, Perry M et al (2008) S-nitrosylated S100A8: novel anti-inflammatory properties. J Immunol 181:5627–5636

    Article  CAS  PubMed  Google Scholar 

  • Lipsky BA, Hoey C (2009) Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis 49:1541–1549

    Article  PubMed  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

    Article  CAS  PubMed  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

    Article  CAS  PubMed  Google Scholar 

  • Lundqvist K, Sørensen OE, Schmidtchen A (2008) Increased levels of human neutrophil alpha-defensins in chronic venous leg ulcers. J Dermatol Sci 51:131–134

    Article  CAS  PubMed  Google Scholar 

  • Maerki C, Meuter S, Liebi M, Muhlemann K, Frederick MJ, Yawalkar N, Moser B, Wolf M (2009) Potent and broad-spectrum antimicrobial activity of CXCL14 suggests an immediate role in skin infections. J Immunol 182:507–514

    Article  CAS  PubMed  Google Scholar 

  • Malmsten M, Davoudi M, Walse B, Rydengard V, Pasupuleti M, Mörgelin M, Schmidtchen A (2007) Antimicrobial peptides derived from growth factors. Growth Factors 25:60–70

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731–2738

    Article  CAS  PubMed  Google Scholar 

  • Miles K, Clarke DJ, Lu W, Sibinska Z, Beaumont PE, Davidson DJ, Barr TA, Campopiano DJ, Gray M (2009) Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol 183:2122–2132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mork G, Schjerven H, Mangschau L, Soyland E, Brandtzaeg P (2003) Proinflammatory cytokines upregulate expression of calprotectin (L1 protein, MRP-8/MRP-14) in cultured human keratinocytes. Br J Dermatol 149:484–491

    Article  CAS  PubMed  Google Scholar 

  • Mullins ES, Kombrinck KW, Talmage KE, Shaw MA, Witte DP, Ullman JM, Degen SJ, Sun W, Flick MJ, Degen JL (2009) Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain. Blood 113:696–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy CJ, Foster BA, Mannis MJ, Selsted ME, Reid TW (1993) Defensins are mitogenic for epithelial cells and fibroblasts. J Cell Physiol 155:408–413

    Article  CAS  PubMed  Google Scholar 

  • Nagaoka I, Tamura H, Hirata M (2006) An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol 176:3044–3052

    Article  CAS  PubMed  Google Scholar 

  • Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L (2005) Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol 124:931–938

    Article  CAS  PubMed  Google Scholar 

  • Nakatsuji T, Chiang HI, Jiang SB, Nagarajan H, Zengler K, Gallo RL (2013) The microbiome extends to subepidermal compartments of normal skin. Nat Commun 4:1431

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nickoloff BJ, Bonish BK, Marble DJ, Schriedel KA, DiPietro LA, Gordon KB, Lingen MW (2006) Lessons learned from psoriatic plaques concerning mechanisms of tissue repair, remodeling, and inflammation. J Investig Dermatol Symp Proc 11:16–29

    Article  CAS  PubMed  Google Scholar 

  • Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, Nagaoka I, Okumura K, Ogawa H (2007) Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 127:594–604

    Article  CAS  PubMed  Google Scholar 

  • Nordahl EA, Rydengard V, Nyberg P, Nitsche DP, Morgelin M, Malmsten M, Bjorck L, Schmidtchen A (2004) Activation of the complement system generates antibacterial peptides. Proc Natl Acad Sci U S A 101:16879–16884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nurjadi D, Herrmann E, Hinderberger I, Zanger P (2013) Impaired beta-defensin expression in human skin links DEFB1 promoter polymorphisms with persistent Staphylococcus aureus nasal carriage. J Infect Dis 207:666–674

    Article  CAS  PubMed  Google Scholar 

  • Ortega-Gomez A, Perretti M, Soehnlein O (2013) Resolution of inflammation: an integrated view. EMBO Mol Med 5:661–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otte JM, Werner I, Brand S, Chromik AM, Schmitz F, Kleine M, Schmidt WE (2008) Human beta defensin 2 promotes intestinal wound healing in vitro. J Cell Biochem 104:2286–2297

    Article  CAS  PubMed  Google Scholar 

  • Påhlman LI, Mörgelin M, Kasetty G, Olin AI, Schmidtchen A, Herwald H (2013) Antimicrobial activity of fibrinogen and fibrinogen-derived peptides – a novel link between coagulation and innate immunity. Thromb Haemost 109:930–939

    Article  PubMed  CAS  Google Scholar 

  • Panyutich P, Shi J, Boutz PL, Zhao C, Ganz T (1997) Porcine polymorphonuclear leukocytes generate extracellular microbial activity by elastase-mediated activation of secreted proprotegrins. Infect Immun 65:978–985

    CAS  PubMed  PubMed Central  Google Scholar 

  • Papareddy P, Rydengard V, Pasupuleti M, Walse B, Morgelin M, Chalupka A, Malmsten M, Schmidtchen A (2010) Proteolysis of human thrombin generates novel host defense peptides. PLoS Pathog 6:e1000857

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pasupuleti M, Walse B, Nordahl EA, Morgelin M, Malmsten M, Schmidtchen A (2007) Preservation of antimicrobial properties of complement peptide C3a, from invertebrates to humans. J Biol Chem 282:2520–2528

    Article  CAS  PubMed  Google Scholar 

  • Raftery MJ, Yang Z, Valenzuela SM, Geczy CL (2001) Novel intra- and inter-molecular sulfinamide bonds in S100A8 produced by hypochlorite oxidation. J Biol Chem 276:33393–33401

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Martinez S, Cancino-Diaz JC, Vargas-Zuniga LM, Cancino-Diaz ME (2008) LL-37 regulates the overexpression of vascular endothelial growth factor (VEGF) and c-IAP-2 in human keratinocytes. Int J Dermatol 47:457–462

    Article  CAS  PubMed  Google Scholar 

  • Röhrl J, Yang D, Oppenheim JJ, Hehlgans T (2010) Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J Immunol 184:6688–6694

    Article  PubMed  CAS  Google Scholar 

  • Roupé KM, Nybo M, Sjöbring U, Alberius P, Schmidtchen A, Sørensen OE (2010) Injury is a major inducer of epidermal innate immune responses during wound healing. J Invest Dermatol 130:1167–1177

    Article  PubMed  CAS  Google Scholar 

  • Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier PA (2003) Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. J Immunol 170:3233–3242

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, Casavant TL, McCray 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scocchi M, Skerlavaj B, Romeo D, Gennaro R (1992) Proteolytic cleavage by neutrophil elastase converts inactive storage proforms to antibacterial bactenecins. Eur J Biochem 209:589–595

    Article  CAS  PubMed  Google Scholar 

  • Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6:1191–1197

    Article  CAS  PubMed  Google Scholar 

  • Shubbar E, Vegfors J, Carlstrom M, Petersson S, Enerback C (2012) Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation. Breast Cancer Res Treat 134:71–80

    Article  CAS  PubMed  Google Scholar 

  • Simanski M, Dressel S, Glaser R, Harder J (2010) RNase 7 protects healthy skin from Staphylococcus aureus colonization. J Invest Dermatol 130:2836–2838

    Article  CAS  PubMed  Google Scholar 

  • Simanski M, Rademacher F, Schroder L, Schumacher HM, Glaser R, Harder J (2013) IL-17A and IFN-gamma synergistically induce RNase 7 expression via STAT3 in primary keratinocytes. PLoS One 8:e59531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simard JC, Simon MM, Tessier PA, Girard D (2011) Damage-associated molecular pattern S100A9 increases bactericidal activity of human neutrophils by enhancing phagocytosis. J Immunol 186:3622–3631

    Article  CAS  PubMed  Google Scholar 

  • Simmaco M, Mignogna G, Barra D (1998) Antimicrobial peptides from amphibian skin: what do they tell us? Biopolymers 47:435–450

    Article  CAS  PubMed  Google Scholar 

  • Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746

    Article  CAS  PubMed  Google Scholar 

  • Soehnlein O, Kai-Larsen Y, Frithiof R, Sorensen OE, Kenne E, Scharffetter-Kochanek K, Eriksson EE, Herwald H, Agerberth B, Lindbom L (2008a) Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest 118:3491–3502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L (2008b) Neutrophil secretion products pave the way for inflammatory monocytes. Blood 112:1461–1471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sonesson A, Ringstad L, Nordahl EA, Malmsten M, Morgelin M, Schmidtchen A (2007) Antifungal activity of C3a and C3a-derived peptides against Candida. Biochim Biophys Acta 1768:346–353

    Article  CAS  PubMed  Google Scholar 

  • Sørensen 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  Google Scholar 

  • Sørensen 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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Sørensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T (2005) Differential regulation of β-defensin expression in human skin by microbial stimuli. J Immunol 174:4870–4879

    Article  PubMed  Google Scholar 

  • Sørensen OE, Thapa DR, Roupe KM, Valore EV, Sjobring U, Roberts AA, Schmidtchen A, Ganz T (2006) Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor. J Clin Invest 116:1878–1885

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sørensen OE, Schmidtchen A, Roupe KM (2008) EGF receptor: role for innate immunity during wound healing in human skin. Expert Rev Dermatol 3:587–593

    Article  CAS  Google Scholar 

  • Sørensen OE, Clemmensen SN, Dahl SL, Østergaard O, Heegaard NH, Glenthøj A, Nielsen FC, Borregaard N (2014) Papillon-Lefevre syndrome patient reveals species-dependent requirements for neutrophil defenses. J Clin Invest 124:4539–4548

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Steinbakk M, Naess-Andresen CF, Lingaas E, Dale I, Brandtzaeg P, Fagerhol MK (1990) Antimicrobial actions of calcium binding leukocyte L1 protein, calprotectin. Lancet 336:763–765

    Article  CAS  PubMed  Google Scholar 

  • Steinstraesser L, Lam MC, Jacobsen F, Porporato PE, Chereddy KK, Becerikli M, Stricker I, Hancock RE, Lehnhardt M, Sonveaux P et al (2014) Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing. Mol Ther 22:734–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Territo MC, Ganz T, Selsted ME, Lehrer RI (1989) Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 84:2017–2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Theilgaard-Mönch K, Knudsen S, Follin P, Borregaard N (2004) The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing. J Immunol 172:7684–7693

    Article  PubMed  Google Scholar 

  • Thorey IS, Roth J, Regenbogen J, Halle JP, Bittner M, Vogl T, Kaesler S, Bugnon P, Reitmaier B, Durka S et al (2001) The Ca2 + −binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes. J Biol Chem 276:35818–35825

    Article  CAS  PubMed  Google Scholar 

  • Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sørensen OE, Borregaard N, Rabe KF, Hiemstra PS (2003) The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 171:6690–6696

    Article  CAS  PubMed  Google Scholar 

  • Tokumaru S, Higashiyama S, Endo T, Nakagawa T, Miyagawa JI, Yamamori K, Hanakawa Y, Ohmoto H, Yoshino K, Shirakata Y et al (2000) Ectodomain shedding of epidermal growth factor receptor ligands is required for keratinocyte migration in cutaneous wound healing. J Cell Biol 151:209–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tokumaru S, Sayama K, Shirakata Y, Komatsuzawa H, Ouhara K, Hanakawa Y, Yahata Y, Dai XJ, Tohyama M, Nagai H et al (2005) Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol 175:4662–4668

    Article  CAS  PubMed  Google Scholar 

  • Tomee JF, Hiemstra PS, Heinzel-Wieland R, Kauffman HF (1997) Antileukoprotease: an endogenous protein in the innate mucosal defense against fungi. J Infect Dis 176:740–747

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, Brinkmann V, Jungblut PR, Zychlinsky A (2009) Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog 5:e1000639

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • vanBergen BH, Andriessen MPM, Spruijt KIJ, van de Kerkhof PCM, Schalkwijk J (1996) Expression of SKALP/elafin during wound healing in human skin. Arch Dermatol Res 288:458–462

    Article  CAS  Google Scholar 

  • Vandal K, Rouleau P, Boivin A, Ryckman C, Talbot M, Tessier PA (2003) Blockade of S100A8 and S100A9 suppresses neutrophil migration in response to lipopolysaccharide. J Immunol 171:2602–2609

    Article  CAS  PubMed  Google Scholar 

  • Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MAD, Nacken W, Foell D, van der Poll T, Sorg C et al (2007) Mrp8 and Mrp14 are endogenous activators of Toll- like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 13:1042–1049

    Article  CAS  PubMed  Google Scholar 

  • Wanke I, Steffen H, Christ C, Krismer B, Gotz F, Peschel A, Schaller M, Schittek B (2011) Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol 131:382–390

    Article  CAS  PubMed  Google Scholar 

  • Ward PA (1968) Chemotaxis of mononuclear cells. J Exp Med 128:1201–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wingens M, van Bergen BH, Hiemstra PS, Meis JF, van Vlijmen WIM, Zeeuwen PL, Mulder J, Kramps HA, van Ruissen F, Schalkwijk J (1998) Induction of SLPI (ALP/HUSI-I) in epidermal keratinocytes. J Invest Dermatol 111:996–1002

    Article  CAS  PubMed  Google Scholar 

  • Wolf R, Howard OM, Dong HF, Voscopoulos C, Boeshans K, Winston J, Divi R, Gunsior M, Goldsmith P, Ahvazi B et al (2008) Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15. J Immunol 181:1499–1506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang D, Chertov O, Bykovskaia N, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OMZ et al (1999) beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525–528

    Article  CAS  PubMed  Google Scholar 

  • Yang D, Chen Q, Chertov O, Oppenheim JJ (2000a) Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol 68:9–14

    CAS  PubMed  Google Scholar 

  • Yang D, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000b) 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 neutrophil, monocytes, and T cells. J Exp Med 192:1069–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Zanger P, Holzer J, Schleucher R, Scherbaum H, Schittek B, Gabrysch S (2010) Severity of Staphylococcus aureus infection of the skin is associated with inducibility of human beta-defensin 3 but not human beta-defensin 2. Infect Immun 78:3112–3117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zanger P, Nurjadi D, Vath B, Kremsner PG (2011) Persistent nasal carriage of Staphylococcus aureus is associated with deficient induction of human beta-defensin 3 after sterile wounding of healthy skin in vivo. Infect Immun 79:2658–2662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zasloff M (1987) Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci U S A 84:5449–5453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu J, Nathan C, Jin W, Sim D, Ashcroft GS, Wahl SM, Lacomis L, Erdjument-Bromage H, Tempst P, Wright CD et al (2002) Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 111:867–878

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the Alfred Österlunds Stiftelse, the Royal Physiografic Society Lund, Greta och Johan Kocks Stiftelse, Petrus och Augusta Hedlunds Stiftelse, and the Swedish Research Council.

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  1. Nuclear Biology Laboratory, Division of Infection Medicine, BMC, B14, Department of Clinical Sciences, Lund University, Tornavägen 10, Lund, SE-221 84, Sweden

    Ole E. Sørensen

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Correspondence to Ole E. Sørensen .

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  1. Department of Dermatology, University-Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Jürgen Harder

  2. Department of Dermatology, University-Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Jens-M. Schröder

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Sørensen, O.E. (2016). Antimicrobial Peptides in Cutaneous Wound Healing. In: Harder, J., Schröder, JM. (eds) Antimicrobial Peptides. Birkhäuser Advances in Infectious Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-24199-9_1

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