Antimicrobial activities of chemokines: Not just a side-effect?

Frontiers in Immunology

Volumn 3, Issue JUL, 2012, Pages

  Wolf, Marlene ^a   Moser, Bernhard ^b  

^a UNIVERSITY OF BERN   (Switzerland)

^b CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Antimicrobial immunity; Antimicrobial peptides; Chemokines; Immune surveillance

Indexed keywords

EID: 84874200596     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00213     Document Type: Review

References (100)

1. Agerberth, B., Charo, J., Werr, J., Ols-son, B., Idali, F., Lindbom, L., Kiessling, R., Jornvall, H., Wigzell, H., and Gudmundsson, G. H. (2000). The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96, 3086-3093
2. Augsten, M., Hagglof, C., Olsson, E., Stolz, C., Tsagozis, P., Levchenko, T., Frederick, M. J., Borg, A., Micke, P., Egevad, L., and Ost-man, A. (2009). CXCL14 is an autocrine growth factor for fibrob-lasts and acts as a multi-modal stimulator of prostate tumor growth. Proc. Natl. Acad. Sci. U.S.A. 106, 3414-3419.
3. Bals, R., and Wilson, J. M. (2003). Cathe-licidins - a family of multifunctional antimicrobial peptides. Cell. Mol. Life Sci. 60,711-720
4. Banisadr, G., Bhattacharyya, B. J., Bel-madani, A., Izen, S. C., Ren, D., Tran, P. B., and Miller, R. J. (2011). The chemokine BRAK/CXCL14 regulates synaptic transmission in the adult mouse dentate gyrus stem cell niche. J. Neurochem. 119, 1173-1182.
5. Bjorstad, A., Fu, H., Karlsson, A., Dahlgren, C., and Bylund, J. (2005). Interleukin-8-derived peptide has antibacterial activity. Antimicrob. Agents Chemother. 49, 3889-3895.
6. Brogden, K. A. (2005). Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3,238-250.
7. Cederlund, A., Gudmundsson, G. H., and Agerberth, B. (2011). Antimicrobial peptides important in innate immunity. FEBS J. 278, 3942-3951.
8. Chan, D. I., Hunter, H. N., Tack, B. E, and Vogel, H. J. (2008). Human macrophage inflammatory protein 3 alpha: protein and peptide nuclear magnetic resonance solution structures, dimerization, dynamics, and anti-infective properties. Antimi-crob. Agents Chemother. 52,883-894.
9. Chertov, O., Michiel, D. F., Xu, L., Wang, J. M., Tani, K., Murphy, W. J., Longo, D. L., Taub, D. D., and Oppenheim, J. J. (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.
10. Chromek, M., Slamova, Z., Bergman, P., Kovacs, L., Podracka, L., Ehren, I., Hokfelt, T., Gudmundsson, G. H., Gallo, R. L., Agerberth, B., and Brauner, A. (2006). The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat. Med. 12, 636-641.
11. Clark-Lewis, I., Dewald, B., Loetscher, M., Moser, B., and Baggiolini, M. (1994). Structural requirements for interleukin-8 function identified by design of analogs and CXC chemokine hybrids. J. Biol. Chem. 269, 16075-16081.
12. Cole, A. M., Ganz, T., Liese, A. M., Bur-dick, M. D., Liu, L., and Strieter, R. M. (2001). Cutting edge: IFN-inducible ELR- CXC chemokines display defensin-like antimicrobial activity. J. Immunol. 167, 623-627.
13. Collin, M., Linge, H. M., Bjartell, A., Giwercman, A., Malm, J., and Egesten, A. (2008). Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract. J. Reprod. Immunol. 79, 37-43.
14. Crawford, M. A., Burdick, M. D., Glomski, I. J., Boyer, A. E., Barr, J. R., Mehrad, B., Strieter, R. M., and Hughes, M. A. (2010). Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection. PLoSPathog. 6,e1001199. doi:10.1371/journal.ppat.1001199
15. Crawford, M. A., Zhu, Y., Green, C. S., Burdick, M. D., Sanz, P., Alem, F., OBrien, A. D., Mehrad, B., Strieter, R. M., and Hughes, M. A. (2009). Antimicrobial effects of interferon-inducible CXC chemokines against Bacillus anthracis spores and bacilli. Infect. Immun. 77, 1664-1678.
16. Davidson, D. J., Currie, A. J., Reid, G. S., Bowdish, D. M., MacDon-ald, K. L., Ma, R. C., Hancock, R. E., and Speert, D. P. (2004). The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J. Immunol. 172, 1146-1156.
17. De, Y., Chen, Q., Schmidt, A. P., Anderson, G. M., Wang, J. M., Woot-ers, J., Oppenheim, J. J., and Chertov, O. (2000). LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL-1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J. Exp. Med. 192, 1069-1074.
18. De Smet, K., and Contreras, R. (2005). Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnol. Lett. 27, 1337-1347.
19. Dorschner, R. A., Lin, K. H., Murakami, M., and Gallo, R. L. (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.
20. Egesten, A., Eliasson, M., Johansson, H. M., Olin, A. I., Morgelin, M., Mueller, A., Pease, J. E., Frick, I. M., and Bjorck, L. (2007). The CXC chemokine MIG/CXCL9 is important in innate immunity against Streptococcuspyogenes. J. Infect. Dis. 195,684-693.
21. Egesten, A., Frick, I. M., Morgelin, M., Olin, A. I., and Bjorck, L. (2011). Binding of albumin promotes bacterial survival at the epithelial surface. J. Biol. Chem. 286, 2469-2476.
22. Egesten, A., Olin, A. I., Linge, H. M., Yadav, M., Morgelin, M., Karlsson, A., and Collin, M. (2009). SpeB of Streptococcus pyogenes differentially modulates antibacterial and receptor activating properties of human chemokines. PLoS ONE 4, e4769. doi:10.1371/journal.pone.0004769
23. Feng, Z., Dubyak, G. R., Lederman, M. M., and Weinberg, A. (2006). Cutting edge: human beta defensin 3 - a novel antagonist of the HIV-1 coreceptor CXCR4. J. Immunol. 177, 782-786.
24. Frederick, M. J., Henderson, Y., Xu, X., Deavers, M. T., Sahin, A. A., Wu, H., Lewis, D. E., El-Naggar, A. K., and Clayman, G. L. (2000). In vivo expression of the novel CXC chemokine BRAK in normal and cancerous human tissue. Am. J. Pathol. 156, 1937-1950.
25. Frick, I. M., Akesson, P., Herwald, H., Morgelin, M., Malmsten, M., Nagler, D. K., and Bjorck, L. (2006). The contact system - a novel branch of innate immunity generating antibacterial peptides. EMBO J. 25,5569-5578.
26. Frick, I. M., Nordin, S. L., Baumgarten, M., Morgelin, M., Sorensen, O. E., Olin, A. I., and 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.
27. Frohm, M., Agerberth, B., Ahangari, G., Stahle-Backdahl, M., Liden, S., Wigzell, H., and Gudmundsson, G. H. (2097). 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.
28. Ganz, T. (2003). Defensins: antimicrobial peptides of innate immunity. Nat. Rev. 3, 710-720.
29. Glaser, R., Harder, J., Lange, H., Bartels, J., Christophers, E., and Schroder, J. M. (2005). Antimicrobial psori-asin (S100A7) protects human skin from Escherichia coli infection. Nat. Immunol. 6, 57-64.
30. Goldman, M. J., Anderson, G. M., Stolzenberg, E. D., Kari, U. P.,Zasloff, M.,andWilson,J.M. (2097).Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88, 553-560.
31. Grigat, J., Soruri, A., Forssmann, U., Riggert, J., and Zwirner, J. (2007). Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family. J. Immunol. 179, 3958-3965.
32. Harder, J., and Schroder, J. M. (2002). RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J. Biol. Chem. 277, 46779-46784.
33. Hasan, L., Mazzucchelli, L., Liebi, M., Lis, M., Hunger, R. E., Tester, A., Overall, C. M., and Wolf, M. (2006). Function of liver activation-regulated chemokine/CC chemokine ligand 20 is differently affected by cathepsin B and cathep-sin D processing. J. Immunol. 176, 6512-6522.
34. Heilborn, J. D., Nilsson, M. F., Kratz, G., Weber, G., Sorensen, O., Bor-regaard, N., and Stahle-Backdahl, M. (2003). The cathelicidin antimicrobial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium.J. Invest. Dermatol. 120,379-389.
35. Hevezi, P., Moyer, B. D., Lu, M., Gao, N., White, E., Echeverri, F., Kala-bat, D., Soto, H., Laita, B., Li, C., Yeh, S. A., Zoller, M., and Zlotnik, A. (2009). Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes. PLoS ONE 4, e6395. doi:10.1371/journal.pone.0006395
36. Hieshima, K., Ohtani, H., Shibano, M., Izawa, D., Nakayama, T., Kawasaki, Y., Shiba, F., Shiota, M., Katou, F., Saito, T., and Yoshie, O. (2003). CCL28 has dual roles in mucosal immunity as a chemokine with broad-spectrum antimicrobial activity.J. Immunol. 170,1452-1461.
37. Hoover, D. M., Boulegue, C., Yang, D., Oppenheim, J. J., Tucker, K., Lu, W., and Lubkowski, J. (2002). The structure of human macrophage inflammatory protein-3alpha/CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins. J. Biol. Chem. 277, 37647-37654.
38. Hoover, D. M., Wu, Z., Tucker, K., Lu, W., and Lubkowski, J. (2003). Antimicrobial characterization of human beta-defensin 3 derivatives. Antimicrob. Agents Chemother. 47, 2804-2809.
39. Hromas, R., Broxmeyer, H. E., Kim, C., Nakshatri, H., Christopherson, K. II, Azam, M., and Hou, Y H. (2099). Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells. Biochem. Biophys. Res. Commun. 255, 703-706.
40. Izadpanah, A., and Gallo, R. L. (2005). Antimicrobial peptides. J. Am. Acad. Dermatol. 52, 381-390; quiz 391-382
41. Kim, B. E., Leung, D. Y., Streib, J. E., Kisich, K., Boguniewicz, M., Hamid, Q. A., and Howell, M. D. (2007). Macrophage inflammatory protein 3alpha deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus. J. Allergy Clin. Immunol. 119,457-463.
42. Kotarsky, K., Sitnik, K. M., Stenstad, H., Kotarsky, H., Schmidtchen, A., Koslowski, M., Wehkamp, J., and Agace,W.W. (2010).Anovelrolefor constitutively expressed epithelial-derived chemokines as antibacterial peptides in the intestinal mucosa. Mucosal Immunol. 3, 40-48.
43. Krijgsveld, J., Zaat, S. A., Meeldijk, J., van Veelen, P. A., Fang, G., Poolman, B., Brandt, E., Ehlert, J. E., Kuijpers, A. J., Engbers, G. H., Feijen, J., and Dankert, J. (2000). Thrombocidins, microbicidal proteins from human blood platelets, are C-terminal deletion products of CXC chemokines. J. Biol. Chem. 275,20374-20381.
44. Kuang, H., Chen, Q., Zhang, Y., Zhang, L., Peng, H., Ning, L., Cao, Y., and Duan, E. (2009). The cytokine gene CXCL14 restricts human tro-phoblast cell invasion by suppressing gelatinase activity. Endocrinology 150,5596-5605.
45. Kurth, I., Willimann, K., Schaerli, P., Hunziker, T., Clark-Lewis, I., and Moser, B. (2001). Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development. J. Exp. Med. 194, 855-861.
46. Lai, Y., and Gallo, R. L. (2009). AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 30,131-141.
47. Lehrer, R. I. (2004). Primate defensins. Nat. Rev. Microbiol. 2, 727-738.
48. Linge, H. M., Collin, M., Norden-felt, P., Morgelin, M., Malmsten, M., and Egesten, A. (2008). The human CXC chemokine granulo-cyte chemotactic protein 2 (GCP-2)/CXCL6 possesses membrane-disrupting properties and is antibacterial. Antimicrob. Agents Chemother. 52,2599-2607.
49. Liu, B., and Wilson, E. (2010). The antimicrobial activity of CCL28 is dependent on C-terminal positively-charged amino acids. Eur. J. Immunol. 40, 186-196.
50. Liu, P. T., Stenger, S., Li, H., Wen-zel, L., Tan, B. H., Krutzik, S. R., Ochoa, M. T., Schauber, J., Wu, K., Meinken, C., Kamen, D. L., Wagner, M., Bals, R., Steinmeyer, A., Zugel, U., Gallo, R. L., Eisenberg, D., Hewi-son, M., Hollis, B. W., Adams, J. S., Bloom, B. R., and Modlin, R. L. (2006). Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 1770-1773.
51. Maerki, C., Meuter, S., Liebi, M., Muhle-mann, K., Frederick, M. J., Yawalkar, N., Moser, B., and Wolf, M. (2009). Potent and broad-spectrum antimicrobial activity of CXCL14 suggests an immediate role in skin infections. J.Immunol. 182,507-514.
52. Martinez-Becerra, F., Silva, D. A., Dominguez-Ramirez, L., Mendoza-Hernandez, G., Lopez-Vidal, Y., Sol-devila, G., and Garcia-Zepeda, E. A. (2007). Analysis of the antimicrobial activities of a chemokine-derived peptide (CDAP-4) on Pseudomonas aeruginosa. Biochem. Biophys. Res. Commun. 355, 352-358.
53. McKinnon, C. M., Lygoe, K. A., Skel-ton, L., Mitter, R., and Mellor, H. (2008). The atypical Rho GTPase RhoBTB2 is required for expression of the chemokine CXCL14 in normal and cancerous epithelial cells. Oncogene 27, 6856-6865.
54. Meuter, S., and Moser, B. (2008). Constitutive expression of CXCL14 in healthy human and murine epithelial tissues. Cytokine 44, 248-255.
55. Meuter, S., Schaerli, P., Roos, R. S., Bran-dau, O., Bosl, M. R., von Andrian, U. H., and Moser, B. (2007). Murine CXCL14 is dispensable for dendritic cell function and localization within peripheral tissues. Mol. Cell. Biol. 27, 983-992.
56. Morrison, G., Kilanowski, F., Davidson, D., and Dorin, J. (2002). Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect. Immun. 70, 3053-3060.
57. Moser, B., Wolf, M., Walz, A., and Loetscher, P. (2004). Chemokines: multiple levels of leukocyte migration control. Trends Immunol. 25, 75-84.
58. Moser, C., Weiner, D. J., Lysenko, E., Bals, R., Weiser, J. N., and Wilson, J. M. (2002). beta-Defensin 1 contributes to pulmonary innate immunity in mice. Infect. Immun. 70, 3068-3072.
59. Mukherjee, S., Vaishnava, S., and Hooper, L. V. (2008). Multi-layered regulation of intestinal antimicrobial defense. Cell. Mol. Life Sci. 65, 3019-3027.
60. Murakami, M., Lopez-Garcia, B., Braff, M., Dorschner, R. A., and Gallo, R. L. (2004). Postsecretory processing generates multiple catheli-cidins for enhanced topical antimicrobial defense. J. Immunol. 172, 3070-3077.
61. Nara, N., Nakayama, Y., Okamoto, S., Tamura, H., Kiyono, M., Muraoka, M., Tanaka, K., Taya, C., Shitara, H., Ishii, R., Yonekawa, H., Minokoshi, Y., and Hara, T. (2007). Disruption of CXC motif chemokine ligand-14 in mice ameliorates obesity-induced insulin resistance. J. Biol. Chem. 282, 30794-30803.
62. Nguyen, L. T., Chan, D. I., Boszhard, L., Zaat, S. A., and Vogel, H. J. (2010). Structure-function studies of chemokine-derived carboxy-terminal antimicrobial peptides. Biochim. Biophys. Acta 1798, 1062-1072.
63. Niyonsaba, F., Iwabuchi, K., Someya, A., Hirata, M., Matsuda, H., Ogawa, H., and Nagaoka, I. (2002). A cathe-licidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106, 20-26.
64. Niyonsaba, F., Ushio, H., Nakano, N., Ng, W., Sayama, K., Hashimoto, K., Nagaoka, I., Okumura, K., and 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.
65. Nizet, V., Ohtake, T., Lauth, X., Trow-bridge, J., Rudisill, J., Dorschner, R. A., Pestonjamasp,V.,Piraino, J.,Hut-tner, K., and Gallo, R. L. (2001). Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414, 454-457.
66. Nomura, I., Gao, B., Boguniewicz, M., Darst, M. A., Travers, J. B., and Leung, D. Y. (2003). Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J. Allergy Clin. Immunol. 112, 1195-1202.
67. Ong, P. Y., Ohtake, T., Brandt, C., Strickland, I., Boguniewicz, M., Ganz, T., Gallo, R. L., and Leung, D. Y. (2002). Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl. J. Med. 347,1151-1160.
68. Ozawa, S., Ito, S., Kato, Y., Kubota, E., and Hata, R. (2010). Human p38 delta MAP kinase mediates UV irradiation induced up-regulation of the gene expression of chemokine BRAK/CXCL14. Biochem. Biophys. Res. Commun. 396,1060-1064.
69. Ozawa, S., Kato, Y., Komori, R., Mae-hata, Y., Kubota, E., and Hata, R. (2006). BRAK/CXCL14 expression suppresses tumor growth in vivo in human oral carcinoma cells. Biochem. Biophys. Res. Commun. 348,406-412.
70. Pelicano, H., Lu, W., Zhou, Y., Zhang, W., Chen, Z., Hu, Y., and Huang, P. (2009). Mitochondrial dysfunction and reactive oxygen species imbalance promote breast cancer cell motility through a CXCL14-mediated mechanism. Cancer Res. 69,2375-2383.
71. Proudfoot, A. E., Handel, T. M., Johnson, Z., Lau, E. K., LiWang, P., Clark-Lewis, I., Borlat, F., Wells, T. N., and Kosco-Vilbois, M. H. (2003). Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines. Proc. Natl. Acad. Sci. U.S.A. 100,1885-1890.
72. Rehaume, L. M., and Hancock, R. E. (2008). Neutrophil-derived defensins as modulators of innate immune function. Crit. Rev. Immunol. 28,185-200.
73. Salogni, L., Musso, T., Bosisio, D., Mirolo, M., Jala, V. R., Haribabu, B., Locati, M., and Sozzani, S. (2009). Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14. Blood 113,5848-5856.
74. Schaerli, P., Willimann, K., Ebert, L. M., Walz,A.,andMoser,B. (2005).Cutaneous CXCL14 targets blood precursors to epidermal niches for Langer-hans cell differentiation. Immunity 23,331-342.
75. Schauber, J., and Gallo, R. L. (2008). The vitamin D pathway: a new target for control of the skins immune response? Exp. Dermatol. 17, 633-639.
76. Schauber, J., and Gallo, R. L. (2009). Antimicrobial peptides and the skin immune defense system. J. Allergy Clin. Immunol. 124,R13-R18.
77. Schittek, B., Hipfel, R., Sauer, B., Bauer, J., Kalbacher, H., Stevanovic, S., Schirle, M., Schroeder, K., Blin, N., Meier, F., Rassner, G., and Garbe, C. (2001). Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat. Immunol. 2,1133-1137.
78. Schmid, C. D., Melchior, B., Masek, K., Puntambekar, S. S., Danielson, P. E., Lo, D. D., Sutcliffe, J. G., and Carson, M. J. (2009). Differential gene expression in LPS/IFNgamma activated microglia and macrophages: in vitro versus in vivo. J. Neurochem. 109(Suppl. 1), 117-125.
79. Schroeder, B. O., Wu, Z., Nuding, S., Groscurth, S., Marcinowski, M., Beisner, J., Buchner, J., Schaller, M., Stange, E. F., and Wehkamp, J. (2011). Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469,419-423.
80. Shellenberger, T. D., Wang, M., Gujrati, M., Jayakumar, A., Strieter, R. M., Burdick, M. D., Ioannides,C. G., Efferson, C. L., El-Naggar, A. K., Roberts, D., Clayman, G. L., and Frederick, M. J. (2004). BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells. Cancer Res. 64, 8262-8270.
81. Shurin, G. V., Ferris, R. L., Tourkova, I. L., Perez, L., Lokshin, A., Balkir, L., Collins, B., Chatta, G. S., and Shurin, M. R. (2005). Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo. J. Immunol. 174, 5490-5498.
82. Simanski, M., Dressel, S., Glaser, R., and Harder, J. (2010). RNase 7 protects healthy skin from Staphylococ-cus aureus colonization. J. Invest. Dermatol. 130,2836-2838.
83. Sleeman, M. A., Fraser, J. K., Murison, J. G., Kelly, S. L., Prestidge, R. L., Palmer, D. J., Watson, J. D., and Kumble, K. D. (2000). B cell- and monocyte-activating chemokine (BMAC), a novel non-ELR alpha-chemokine. Int. Immunol. 12, 677-689.
84. Sorensen, O. E., Follin, P., Johnsen, A. H., Calafat, J., Tjabringa, G. S., Hiemstra, P. S., and 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.
85. Soruri, A., Grigat, J., Forssmann, U., Riggert, J., and Zwirner, J. (2007). beta-Defensins chemoat-tract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved. Eur. J. Immunol. 37, 2474-2486.
86. Tanegashima, K., Okamoto, S., Nakayama, Y., Taya, C., Shi-tara, H., Ishii, R., Yonekawa, H., Minokoshi, Y., and Hara, T. (2010). CXCL14 deficiency in mice attenuates obesity and inhibits feeding behavior in a novel environment. PLoS ONE 5, e10321. doi:10.1371/journal.pone.00 10321
87. Territo, M. C., Ganz, T., Selsted, M. E., and Lehrer, R. (2089). Monocyte-chemotactic activity of defensins from human neutrophils. J. Clin. Invest. 84,2017-2020.
88. Travis, S. M., Anderson, N. N., Forsyth, W. R., Espiritu, C., Conway, B. D., Greenberg, E. P., McCray, P. B. Jr., Lehrer, R. I., Welsh, M. J., and Tack, B. F. (2000). Bactericidal activity of mammalian cathelicidin-derived peptides. Infect. Immun. 68, 2748-2755.
89. Wente, M. N., Mayer, C., Gaida, M. M., Michalski, C. W., Giese, T., Bergmann, F., Giese, N. A., Buchler, M. W., and Friess, H. (2008). CXCL14 expression and potential function in pancreatic cancer. Cancer Lett. 259, 209-217.
90. Wiesner, J., and Vilcinskas, A. (2010). Antimicrobial peptides: the ancient arm of the human immune system. Virulence 1,440-464.
91. Wu, Z., Hoover, D. M., Yang, D., Boulegue, C., Santamaria, F., Oppenheim, J. J., Lubkowski, J., and Lu, W . (2003). Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc. Natl. Acad. Sci. U.S.A. 100, 8880-8885.
92. Yamamoto, T., Yamashita, A., Yamada, K., and Hata, R. (2011). Immuno-histochemical localization of chemokine CXCL14 in rat hypo-thalamic neurons. Neurosci. Lett. 487,335-340.
93. Yamasaki, K., Schauber, J., Coda, A., Lin, H., Dorschner, R. A., Schechter, N. M., Bonnart, C., Descargues, P., Hov-nanian, A., and Gallo, R. L. (2006). Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J. 20, 2068-2080.
94. Yang, D., Chen, Q., Chertov, O., and Oppenheim, J. J. (2000). Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J. Leukoc. Biol. 68, 9-14.
95. Yang, D., Chen, Q., Hoover, D. M., Staley, P., Tucker, K. D., Lubkowski, J., and Oppenheim, J. J. (2003). Many chemokines including CCL20/MIP-3alpha display antimicrobial activity. J. Leukoc. Biol. 74, 448-455.
96. Yang, D., Chertov, O., Bykovskaia, S. N., Chen, Q., Buffo, M. J., Shogan, J., Anderson, M., Schroder, J. M., Wang, J. M., Howard, O. M., and Oppenheim, J. J. (2099). Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286, 525-528.
97. Zanetti, M. (2004). Cathelicidins, multifunctional peptides of the innate immunity. J. Leukoc. Biol. 75, 39-48.
98. Zasloff, M. (2002). Antimicrobial peptides of multicellular organisms. Nature 415, 389-395.
99. Zasloff, M. (2009). Antimicrobial RNases of human skin. J. Invest. Dermatol. 129, 2091-2093.
100. Zeya, H. I., and Spitznagel, J. K. (2063). Antibacterial and enzymic basic proteins from leukocyte lysosomes: separation and identification. Science 142, 1085-1087.