Abstract
Endogenous antimicrobial peptides (AMPs)mediate innate immunity in every species in which they have been investigated. Cathelicidins and defensins are the two major AMP families in mammals, and they are abundant components of phagocytic leukocytes and are released by epithelial cells at mucosal surfaces. In the small intestine, Paneth cells at the base of the crypts of Lieberkühn secrete α-defensins and additional AMPs at high levels in response to cholinergic stimulation and when exposed to bacterial antigens. Paneth cell α-defensins evolved to function in the extracellular environment with broad-spectrum antimicrobial activities, and they constitute the majority of bactericidal peptide activity secreted by Paneth cells. The release of Paneth cell products into the crypt lumen is inferred to protect mitotically active crypt cells from colonization by potential pathogens and confers protection from enteric infection, as is evident from the immunity of mice expressing a human Paneth cell α-defensin transgene to oral infection by Salmonella enterica serovar Typhimurium. α-Defensins in Paneth cell secretions also may interact with bacteria in the intestinal lumen above the crypt-villus boundary and influence the composition of the enteric microbial flora. Mutations that cause defects in the activation, secretion, dissolution, and bactericidal effects of Paneth cell AMPs may alter crypt innate immunity and contribute to immunopathology.
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References
Abuja PM, Zenz A, Trabi M, Craik DJ, Lohner K (2004) The cyclic antimicrobial peptide RTD-1 induces stabilized lipid-peptide domains more efficiently than its open-chain analogue. FEBS Lett 566:301–306
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
Andreu P, Colnot S, Godard C, Gad S, Chafey P, Niwa-Kawakita M, Laurent-Puig P, Kahn A, Robine S, Perret C, Romagnolo B (2005) Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development 132:1443–1451
Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ (2000) Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 1:113–118
Ayabe T, Satchell DP, Pesendorfer P, Tanabe H, Wilson CL, Hagen SJ, Ouellette AJ (2002) Activation of Paneth cell alpha-defensins in mouse small intestine. J Biol Chem 277:5219–5228
Bateman A, MacLeod RJ, Lembessis P, Hu J, Esch F, Solomon S (1996) The isolation and characterization of a novel corticostatin/defensin-like peptide from the kidney. J Biol Chem 271:10654–10659
Bevins CL, Jones DE, Dutra A, Schaffzin J, Muenke M (1996) Human enteric defensin genes: chromosomal map position and amodel for possible evolutionary relationships. Genomics 31:95–106
Bevins CL, Martin-Porter E, Ganz T (1999) Defensins and innate host defence of the gastrointestinal tract. Gut 45:911–915
Bevins CL (2004) The Paneth cell and the innate immune response. Curr Opin Gastroenterol 20:572–580
Bjerknes M, Cheng H (1981) The stem-cell zone of the small intestinal epithelium. I. Evidence from Paneth cells in the adult mouse. Am J Anat 160:51–63
Boman HG (1995) Peptide antibiotics and their role in innate immunity. Annu Rev Immunol 13:61–92
Brogden KA (2005) Antimicrobial peptides: pore formers ormetabolic inhibitors in bacteria? Nat Rev Microbiol 3:238–250
Bry L, Falk P, Huttner K, Ouellette A, Midtvedt T, Gordon JI (1994) Paneth cell differentiation in the developing intestine of normal and transgenic mice. Proc Natl Acad Sci U S A 91:10335–10339
Chalifour A, Jeannin P, Gauchat JF, Blaecke A, Malissard M, N’Guyen T, Thieblemont N, Delneste Y (2004) Direct bacterial protein PAMPs recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood 104:1778–1783
Cheng H (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. IV. Paneth cells. Am J Anat 141:521–535
Clarke LL, Gawenis LR, Bradford EM, Judd LM, Boyle KT, Simpson JE, Shull GE, Tanabe H, Ouellette AJ, Franklin CL, Walker NM (2004) Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice. Am J Physiol Gastrointest Liver Physiol 286:G1050–G1058
Cole AM, Hong T, Boo LM, Nguyen T, Zhao C, Bristol G, Zack JA, Waring AJ, Yang OO, Lehrer RI (2002) Retrocyclin: a primate peptide that protects cells from infection by T-and M-tropic strains of HIV-1. Proc Natl Acad Sci U S A 99:1813–1818
Com E, Bourgeon F, Evrard B, Ganz T, Colleu D, Jegou B, Pineau C (2003) Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans. Biol Reprod 68:95–104
Condon MR, Viera A, D’Alessio M, Diamond G (1999) Induction of a rat enteric defensin gene by hemorrhagic shock. Infect Immun 67:4787–4793
Cunliffe RN, Rose FR, Keyte J, Abberley L, Chan WC, Mahida YR (2001) Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut 48:176–185
Darmoul D, Brown D, Selsted ME, Ouellette AJ (1997) Cryptdin gene expression in developing mouse small intestine. Am J Physiol 272:G197–G206
Diamond G, Zasloff M, Eck H, Brasseur M, Maloy WL, Bevins CL (1991) Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A 88:3952–3956
Diamond G, Bevins CL (1994) Endotoxin upregulates expression of an antimicrobial peptide gene in mammalian airway epithelial cells. Chest 105:51S–52S
Eisenhauer PB, Lehrer RI (1992) Mouse neutrophils lack defensins. Infect Immun 60:3446–3447
Falk PG, Hooper LV, Midtvedt T, Gordon JI (1998) Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology. Microbiol Mol Biol Rev 62:1157–1170
Frye M, Bargon J, Dauletbaev N, Weber A, Wagner TO, Gropp R (2000) Expression of human alpha-defensin 5 (HD5) mRNA in nasal and bronchial epithelial cells. J Clin Pathol 53:770–773
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
Ganz T, Sherman MP, Selsted ME, Lehrer RI (1985) Newborn rabbit alveolar macrophages are deficient in two microbicidal cationic peptides, MCP-1 and MCP-2. Am Rev Respir Dis 132:901–904
Ganz T, Liu L, Valore EV, Oren A (1993) Posttranslational processing and targeting of transgenic human defensin in murine granulocyte, macrophage, fibroblast, and pituitary adenoma cell lines. Blood 82:641–650
Ganz T (1994) Biosynthesis of defensins and other antimicrobial peptides. Ciba Found Symp 186:62–71; discussion 71–76
Ganz T (1999) Defensins and host defense. Science 286:420–421
Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3:710–720
Garabedian EM, Roberts LJ, McNevin MS, Gordon JI (1997) Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice. J Biol Chem 272:23729–23740
Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL (2002) Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 3:583–590
Gordon JI, Hermiston ML (1994) Differentiation and self-renewal in the mouse gastrointestinal epithelium. Curr Opin Cell Biol 6:795–803
Grandjean V, Vincent S, Martin L, Rassoulzadegan M, Cuzin F (1997) Antimicrobial protection of the mouse testis: synthesis of defensins of the cryptdin family. Biol Reprod 57:1115–1122
Harder J, Schroder JM (2005) Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins. J Leukoc Biol 77:476–486
He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM, Mishina Y, Li L (2004) BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 36:1117–1121
Hill CP, Yee J, Selsted ME, Eisenberg D (1991) Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science 251:1481–1485
Hiratsuka T, Nakazato M, Date Y, Ashitani J, Minematsu T, Chino N, Matsukura S (1998) Identification of human beta-defensin-2 in respiratory tract and plasma and its increase in bacterial pneumonia. Biochem Biophys Res Commun 249:943–947
Hiratsuka T, Nakazato M, Ihi T, Minematsu T, Chino N, Nakanishi T, Shimizu A, Kangawa K, Matsukura S (2000) Structural analysis of human beta-defensin-1 and its significance in urinary tract infection. Nephron 85:34–40
Hiratsuka T, Mukae H, Iiboshi H, Ashitani J, Nabeshima K, Minematsu T, Chino N, Ihi T, Kohno S, Nakazato M (2003) Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Thorax 58:425–430
Hoffmann JA (2004) Primitive immune systems. Immunol Rev 198:5–9
Hooper LV, Stappenbeck TS, Hong CV, Gordon JI (2003) Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 4:269–273
Hoover DM, Rajashankar KR, Blumenthal R, Puri A, Oppenheim JJ, Chertov O, Lubkowski J (2000) The structure of human beta-defensin-2 shows evidence of higher order oligomerization. J Biol Chem 275:32911–32918
Hoover DM, Chertov O, Lubkowski J (2001) The structure of human beta-defensin-1. New insights into structural properties of beta-defensins. J Biol Chem 276:39021–29026
Hornef MW, Putsep K, Karlsson J, Refai E, Andersson M (2004) Increased diversity of intestinal antimicrobial peptides by covalent dimer formation. Nat Immunol 5:836–843
Hristova K, Selsted ME, White SH (1996) Interactions of monomeric rabbit neutrophil defensinswith bilayers: comparison with dimeric human defensin HNP-2. Biochemistry 35:11888–11894
Hristova K, Selsted ME, White SH (1997) Critical role of lipid composition in membrane permeabilization by rabbit neutrophil defensins. J Biol Chem 272:24224–24233
Huang HW (1999) Peptide-lipid interactions and mechanisms of antimicrobial peptides. Novartis Found Symp 225:188–200; discussion 200–206
Huttner KM, Ouellette AJ (1994) A family of defensin-like genes codes for diverse cysteine-rich peptides in mouse Paneth cells. Genomics 24:99–109
Huttner KM, Selsted ME, Ouellette AJ (1994) Structure and diversity of themurine cryptdin gene family. Genomics 19:448–453
Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, Kagnoff MF (2005) Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol 174:4901–4907
Jing W, Hunter HN, Tanabe H, Ouellette AJ, Vogel HJ (2004) Solution structure of cryptdin-4, a mouse Paneth cell alpha-defensin. Biochemistry 43:15759–15766
Jones DE, Bevins CL (1992) Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 267:23216–23225
Jones DE, Bevins CL (1993) Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett 315:187–192
Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S (2003) Crohn’s disease and the NOD2 gene: a role for Paneth cells. Gastroenterology 125:47–57
Lee PH, Ohtake T, Zaiou M, Murakami M, Rudisill JA, Lin KH, Gallo RL (2005) Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection. Proc Natl Acad Sci U S A 102:3750–3755
Lehrer RI, Selsted ME, Szklarek D, Fleischmann J (1983) Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages. Infect Immun 42:10–14
Lehrer RI, Ganz T, Selsted ME (1988) Oxygen-independent bactericidal systems. Mechanisms and disorders. Hematol Oncol Clin North Am 2:159–169
Lehrer RI, Barton A, Daher KA, Harwig SS, Ganz T, Selsted ME (1989) Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest 84:553–561
Lehrer RI, Ganz T (2002) Defensins of vertebrate animals. Curr Opin Immunol 14:96–102
Lehrer RI, Ganz T (2002) Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 9:18–22
Lehrer RI (2004) Primate defensins. Nat Rev Microbiol 2:727–738
Leonova L, Kokryakov VN, Aleshina G, Hong T, Nguyen T, Zhao C, Waring AJ, Lehrer RI (2001) Circular minidefensins and posttranslational generation of molecular diversity. J Leukoc Biol 70:461–464
Lin MY, Munshi IA, Ouellette AJ (1992) The defensin-related murine CRS1C gene: expression in Paneth cells and linkage to Defcr, the cryptdin locus. Genomics 14:363–368
Linzmeier R, Michaelson D, Liu L, Ganz T (1993) The structure of neutrophil defensin genes. FEBS Lett 321:267–273
Mackewicz CE, Yuan J, Tran P, Diaz L, Mack E, Selsted ME, Levy JA (2003) Alpha-defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. Aids 17:F23–F32
Maemoto A, Qu X, Rosengren KJ, Tanabe H, Henschen-Edman A, Craik DJ, Ouellette AJ (2004) Functional analysis of the alpha-defensin disulfide array in mouse cryptdin-4. J Biol Chem 279:44188–44196
Mallow EB, Harris A, Salzman N, Russell JP, DeBerardinis RJ, Ruchelli E, Bevins CL (1996) Human enteric defensins. Gene structure and developmental expression. J Biol Chem 271:4038–4045
Mambula SS, Simons ER, Hastey R, Selsted ME, Levitz SM (2000) Human neutrophil-mediated nonoxidative antifungal activity against Cryptococcus neoformans. Infect Immun 68:6257–6264
Matsuzaki K, Mitani Y, Akada KY, Murase O, Yoneyama S, Zasloff M, Miyajima K (1998) Mechanism of synergism between antimicrobial peptides magainin 2 and PGLa. Biochemistry 37:15144–15153
Michaelson D, Rayner J, Couto M, Ganz T (1992) Cationic defensins arise from charge-neutralized propeptides: a mechanism for avoiding leukocyte autocytotoxicity? J Leukoc Biol 51:634–639
Newman SL, Gootee L, Gabay JE, Selsted ME (2000) Identification of constituents of human neutrophil azurophil granules that mediate fungistasis against Histoplasma capsulatum. Infect Immun 68:5668–5672
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
Norkina O, Burnett TG, De Lisle RC (2004) Bacterial overgrowth in the cystic fibrosis transmembrane conductance regulator null mouse small intestine. Infect Immun 72:6040–6049
Obata-Onai A, Hashimoto S, Onai N, Kurachi M, Nagai S, Shizuno K, Nagahata T, Mathushima K (2002) Comprehensive gene expression analysis of human NK cells and CD8(+) T lymphocytes. Int Immunol 14:1085–1098
Ouellette AJ, Pravtcheva D, Ruddle FH, James M (1989) Localization of the cryptdin locus on mouse chromosome 8. Genomics 5:233–239
Ouellette AJ, Lualdi JC (1990) A novel mouse gene family coding for cationic, cysteine-rich peptides. Regulation in small intestine and cells of myeloid origin. J Biol Chem 265:9831–9837
Ouellette AJ, Hsieh MM, Nosek MT, Cano-Gauci DF, Huttner KM, Buick RN, Selsted ME (1994) Mouse Paneth cell defensins: primary structures and antibacterial activities of numerous cryptdin isoforms. Infect Immun 62:5040–5047
Ouellette AJ, Lauldi JC (1994) A novel gene family coding for cationic, cysteine-rich peptides. Regulation in mouse small intestine and cells of myeloid origin. J Biol Chem 269:18702
Ouellette AJ, Selsted ME (1996) Paneth cell defensins: endogenous peptide components of intestinal host defense. FASEB J 10:1280–1289
Ouellette AJ, Darmoul D, Tran D, Huttner KM, Yuan J, Selsted ME (1999) Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse Paneth cell alpha-defensin. Infect Immun 67:6643–6651
Ouellette AJ, Satchell DP, Hsieh MM, Hagen SJ, Selsted ME (2000) Characterization of luminal Paneth cell alpha-defensins in mouse small intestine. Attenuated antimicrobial activities of peptides with truncated amino termini. J Biol Chem275:33969–33973
Ouellette AJ, Bevins CL (2001) Paneth cell defensins and innate immunity of the small bowel. Inflamm Bowel Dis 7:43–50
Panyutich A, Shi J, Boutz PL, Zhao C, Ganz T (1997) Porcine polymorphonuclear leukocytes generate extracellular microbicidal activity by elastase-mediated activation of secreted proprotegrins. Infect Immun 65:978–985
Pardi A, Zhang XL, Selsted ME, Skalicky JJ, Yip PF (1992) NMR studies of defensin antimicrobial peptides. 2. Three-dimensional structures of rabbit NP-2 and human HNP-1. Biochemistry 31:11357–11364
Patil A, Hughes AL, Zhang G (2004) Rapid evolution and diversification of mammalian alpha-defensins as revealed by comparative analysis of rodent and primate genes. Physiol Genomics 20:1–11
Peeters T, Vantrappen G (1975) The Paneth cell: a source of intestinal lysozyme. Gut 16:553–558
Pinto D, Clevers H (2005) Wnt control of stem cells and differentiation in the intestinal epithelium. Exp Cell Res 306:357–363
Porter EM, Liu L, Oren A, Anton PA, Ganz T (1997) Localization of human intestinal defensin 5 in Paneth cell granules. Infect Immun 65:2389–2395
Porter EM, Bevins CL, Ghosh D, Ganz T (2002) The multifaceted Paneth cell. Cell Mol Life Sci 59:156–170
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
Rice WG, Ganz T, Kinkade JM Jr, Selsted ME, Lehrer RI, Parmley RT (1987) Defensin-rich dense granules of human neutrophils. Blood 70:757–765
Rodriguez-Jimenez FJ, Krause A, Schulz S, Forssmann WG, Conejo-Garcia JR, Schreeb R, Motzkus D (2003) Distribution of new human beta-defensin genes clustered on chromosome 20 in functionally different segments of epididymis. Genomics 81:175–183
Ross DJ, Cole AM, Yoshioka D, Park AK, Belperio JA, Laks H, Strieter RM, Lynch JP 3rd, Kubak B, Ardehali A, Ganz T (2004) Increased bronchoalveolar lavage human beta-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation. Transplantation 78:1222–1224
Salzman NH, Polin RA, Harris MC, Ruchelli E, Hebra A, Zirin-Butler S, Jawad A, Martin Porter E, Bevins CL (1998) Enteric defensin expression in necrotizing enterocolitis. Pediatr Res 44:20–26
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
Satchell DP, Sheynis T, Kolusheva S, Cummings JE, Vanderlick TK, Jelinek R, Selsted ME, Ouellette AJ (2003) Quantitative interactions between cryptdin-4 amino terminal variants and membranes. Peptides 24:1793–1803
Satchell DP, Sheynis T, Shirafuji Y, Kolusheva S, Ouellette AJ, Jelinek R (2003) Interactions of mouse Paneth cell alpha-defensins and alpha-defensin precursors with membranes: prosegment inhibition of peptide association with biomimetic membranes. J Biol Chem 278:13838–13846
Sawai MV, Jia HP, Liu L, Aseyev V, Wiencek JM, McCray PB Jr, Ganz T, Kearney WR, Tack BF (2001) The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment. Biochemistry 40:3810–3816
Scheetz T, Bartlett JA, Walters JD, Schutte BC, Casavant TL, McCray PB Jr (2002) Genomics-based approaches to gene discovery in innate immunity. Immunol Rev 190:137–145
Schonwetter BS, Stolzenberg ED, Zasloff MA (1995) Epithelial antibiotics induced at sites of inflammation. Science 267:1645–1648
Schreiber S, Rosenstiel P, Albrecht M, Hampe J, Krawczak M (2005) Genetics of Crohn disease, an archetypal inflammatory barrier disease. Nat Rev Genet 6:376–388
Schutte BC, McCray PB Jr (2002) Beta-defensins in lung host defense. Annu Rev Physiol 64:709–748
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
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
Selsted ME, Brown DM, DeLange RJ, Lehrer RI (1983) Primary structures of MCP-1 and MCP-2, natural peptide antibiotics of rabbit lung macrophages. J Biol Chem 258:14485–14489
Selsted ME, Harwig SS, Ganz T, Schilling JW, Lehrer RI (1985) Primary structures of three human neutrophil defensins. J Clin Invest 76:1436–1439
Selsted ME, Harwig SS (1989) Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide. J Biol Chem 264:4003–4007
Selsted ME, Miller SI, Henschen AH, Ouellette AJ (1992) Enteric defensins: antibiotic peptide components of intestinal host defense. J Cell Biol 118:929–936
Selsted ME, Tang YQ, Morris WL, McGuire PA, Novotny MJ, Smith W, Henschen AH, Cullor JS (1993) Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. J Biol Chem 268:6641–6648
Selsted ME, Ouellette AJ (1995) Defensins in granules of phagocytic and nonphagocytic cells. Trends Cell Biol 5:114–119
Selsted ME, Tang YQ, Morris WL, McGuire PA, Novotny MJ, Smith W, Henschen AH, Cullor JS (1996) Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. J Biol Chem 271:16430
Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6:551–557
Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1462:55–70
Shinnar AE, Butler KL, Park HJ (2003) Cathelicidin family of antimicrobial peptides: proteolytic processing and protease resistance. Bioorg Chem 31:425–436
Shirafuji Y, Tanabe H, Satchell DP, Henschen-Edman A, Wilson CL, Ouellette AJ (2003) Structural determinants of procryptdin recognition and cleavage by matrix metalloproteinase-7. J Biol Chem 278:7910–7919
Simon TC, Gordon JI (1995) Intestinal epithelial cell differentiation: new insights from mice, flies and nematodes. Curr Opin Genet Devel 5:577–586
Skalicky JJ, Selsted ME, Pardi A (1994) Structure and dynamics of the neutrophil defensins NP-2, NP-5, and HNP-1: NMR studies of amide hydrogen exchange kinetics. Proteins 20:52–67
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
Sorensen OE, Gram L, Johnsen AH, Andersson E, Bangsboll S, Tjabringa GS, Hiemstra PS, Malm J, Egesten A, Borregaard N (2003) Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. J Biol Chem 278:28540–28546
Sparkes RS, Kronenberg M, Heinzmann C, Daher KA, Klisak I, Ganz T, Mohandas T (1989) Assignment of defensin gene(s) to human chromosome 8p23. Genomics 5:240–244
Stappenbeck TS, Hooper LV, Gordon JI (2002) Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A 99:15451–15455
Stappenbeck TS, Hooper LV, Manchester JK, Wong MH, Gordon JI (2002) Laser capture microdissection of mouse intestine: characterizing mRNA and protein expression, and profiling intermediary metabolism in specified cell populations. Methods Enzymol 356:167–196
Stappenbeck TS, Mills JC, Gordon JI (2003) Molecular features of adult mouse small intestinal epithelial progenitors. Proc Natl Acad Sci U S A 100:1004–1009
Svinarich DM, Wolf NA, Gomez R, Gonik B, Romero R (1997) Detection of human defensin 5 in reproductive tissues. Am J Obstet Gynecol 176:470–475
Tanabe H, Ouellette AJ, Cocco MJ, Robinson WE Jr (2004) Differential effects on human immunodeficiency virus type 1 replication by alpha-defensins with comparable bactericidal activities. J Virol 78:11622–11631
Tanabe H, Yuan J, Zaragoza MM, Dandekar S, Henschen-Edman A, Selsted ME, Ouellette AJ (2004) Paneth cell alpha-defensins fromrhesusmacaque small intestine. Infect Immun 72:1470–1478
Tang YQ, Selsted ME (1993) Characterization of the disulfide motif in BNBD-12, an antimicrobial beta-defensin peptide from bovine neutrophils. J Biol Chem 268:6649–6653
Tang YQ, Yuan J, Miller CJ, Selsted ME (1999) Isolation, characterization, cDNA cloning, and antimicrobial properties of two distinct subfamilies of alpha-defensins from rhesus macaque leukocytes. Infect Immun 67:6139–6144
Tang YQ, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, Ouellette AJ, Selsted ME (1999) A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science 286:498–502
Tomasinsig L, Zanetti M (2005) The cathelicidins—structure, function and evolution. Curr Protein Pept Sci 6:23–34
Trabi M, Schirra HJ, Craik DJ (2001) Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes. Biochemistry 40:4211–4221
Tran D, Tran PA, Tang YQ, Yuan J, Cole T, Selsted ME (2002) Homodimeric thetadefensins from rhesus macaque leukocytes: isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J Biol Chem 277:3079–3084
Valore EV, Ganz T (1992) Posttranslational processing of defensins in immature human myeloid cells. Blood 79:1538–1544
Valore EV, Martin E, Harwig SS, Ganz T (1996) Intramolecular inhibition of human defensin HNP-1 by its propiece. J Clin Invest 97:1624–1629
Van Es JH, Jay P, Gregorieff A, van Gijn ME, Jonkheer S, Hatzis P, Thiele A, van den Born M, Begthel H, Brabletz T, Taketo MM, Clevers H (2005) Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol 7:381–386
Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M, Herrlinger KR, Stallmach A, Noack F, Fritz P, Schroder JM, Bevins CL, Fellermann K, Stange EF (2004) NOD2 (CARD15) mutations in Crohn’s disease are associated with diminished mucosal alpha-defensin expression. Gut 53:1658–1664
White SH, Wimley WC, Selsted ME (1995) Structure, function, and membrane integration of defensins. Curr Opin Struct Biol 5:521–527
Wilson CL, Heppner KJ, Rudolph LA, Matrisian LM (1995) The metalloproteinase matrilysin is preferentially expressed by epithelial cells in a tissue-restricted pattern in the mouse. Mol Biol Cell 6:851–869
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
Wimley WC, Selsted ME, White SH (1994) Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores. Protein Sci 3:1362–1373
Wu ER, Daniel R, Bateman A (1998) RK-2: a novel rabbit kidney defensin and its implications for renal host defense. Peptides 19:793–799
Yamamoto CM, Banaiee N, Yount NY, Patel B, Selsted ME (2004) Alpha-defensin expression during myelopoiesis: identification of cis and trans elements that regulate expression of NP-3 in rat promyelocytes. J Leukoc Biol 75:332–341
Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ (2004) Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 22:181–215
Yenugu S, Hamil KG, Radhakrishnan Y, French FS, Hall SH (2004) The androgen-regulated epididymal sperm-binding protein, human beta-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial beta-defensin. Endocrinology 145:3165–3173
Yount NY, Wang MS, Yuan J, Banaiee N, Ouellette AJ, Selsted ME (1995) Rat neutrophil defensins. Precursor structures and expression during neutrophilic myelopoiesis. J Immunol 155:4476–4484
Yudin AI, Tollner TL, Li MW, Treece CA, Overstreet JW, Cherr GN (2003) ESP13.2, amember of the beta defensin family, is a macaque sperm surface coating protein involved in the capacitation process. Biol Reprod 69:1118–1128
Zanetti M, Gennaro R, Romeo D (1997) The cathelicidin family of antimicrobial peptide precursors: a component of the oxygen-independent defense mechanisms of neutrophils. Ann N Y Acad Sci 832:147–162
Zanetti M, Gennaro R, Scocchi M, Skerlavaj B (2000) Structure and biology of cathelicidins. Adv Exp Med Biol 479:203–218
Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395
Zasloff M (2002) Antimicrobial peptides in health and disease. N Engl J Med 347:1199–1200
Zeya HI, Spitznagel JK (1963) Antibacterial and enzymic basic proteins from leukocyte lysosomes: separation and identification. Science 142:1085–1087
Zeya HI, Spitznagel JK (1966) Cationic proteins of polymorphonuclear leukocyte lysosomes. I. Resolution of antibacterial and enzymatic activities. J Bacteriol 91:750–754
Zeya HI, Spitznagel JK (1966) Cationic proteins of polymorphonuclear leukocyte lysosomes. II. Composition, properties, and mechanism of antibacterial action. J Bacteriol 91:755–762
Zhou CX, Zhang YL, Xiao L, Zheng M, Leung KM, Chan MY, Lo PS, Tsang LL, Wong HY, Ho LS, Chung YW, Chan HC (2004) An epididymis-specific beta-defensin is important for the initiation of sperm maturation. Nat Cell Biol 6:458–464
Zimmermann GR, Legault P, Selsted ME, Pardi A (1995) Solution structure of bovine neutrophil beta-defensin-12: the peptide fold of the beta-defensins is identical to that of the classical defensins. Biochemistry 34:13663–13671
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Ouellette, A.J. (2006). Paneth Cell α-Defensin Synthesis and Function. 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_1
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