Cathelicidins and defensins regulate mast cell antimicrobial activity

COMMENTARY ON THE LAW

Cathelicidins and defensins regulate mast cell antimicrobial activity

Justyna Agier 1 , Ewa Brzezińska-Błaszczyk 1

1. Zakład Immunologii Doświadczalnej, Uniwersytet Medyczny w Łodzi

Published: 2016-06-16
DOI: 10.5604/17322693.1205357
GICID: 01.3001.0009.6842
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2016; 70 : 618-636

 

Abstract

Cathelicidins and defensins are the multifunctional host defense molecules essential for immune response to infection. In recent years they have been shown to be natural, broad-spectrum antimicrobials against both Gram-positive and Gram-negative bacteria, enveloped viruses, and fungi. These small peptides kill the invaded pathogens by destroying their cell membranes and can neutralize biological activities of endotoxin. Apart from exerting direct antimicrobial effects, cathelicidins and defensins can also trigger innate and adaptive defense responses in the host. The functions of the host derived peptides in immunomodulation have been also investigated. Reported activities of these peptides include chemoattractant function, inhibition of neutrophil apoptosis, and ROS production. These peptides directly activate inflammatory cells to production and release of different pro-inflammatory and immunoregulatory mediators, cytokines, and chemokines, however cathelicidins and defensins might mediate the generation of anti-inflammatory cytokines, as well. Insights into the miscellaneous functions of mast cells have exposed that they possess the ability to respond to pathogens and modulate immune response. These immune sentinel cells play a pivotal role in defense mechanisms mainly through the presence of pattern recognition receptors and by release different preformed and newly synthesized mediators and cytokines. The present review provides an introduction to the field of cathelicidins and defensins in general and discusses their impact on mast cells.

References

  • 1. Aarbiou J., Ertmann M., van Wetering S., van Noort P., Rook D.,Rabe K.F., Litvinov S.V., van Krieken J.H., de Boer W.I., Hiemstra P.S.:Human neutrophil defensins induce lung epithelial cell proliferationin vitro. J. Leukoc. Biol., 2002; 72: 167-174
    Google Scholar
  • 2. Aarbiou J., Verhoosel R.M., van Wetering S., de Boer W.I., van KriekenJ.H., Litvinov S.V., Rabe K.F., Hiemstra P.S.: Neutrophil defensinsenhance lung epithelial wound closure and mucin gene expressionin vitro. Am. J. Respir. Cell. Mol. Biol., 2004; 30: 193-201
    Google Scholar
  • 3. Alalwani S.M., Sierigk J., Herr C., Pinkenburg O., Gallo R., VogelmeierC., Bals R.: The antimicrobial peptide LL-37 modulates the inflammatoryand host defense response of human neutrophils. Eur.J. Immunol., 2010; 40: 1118-1126
    Google Scholar
  • 4. Bandholtz L., Ekman G.J., Vilhelmsson M., Buentke E., AgerberthB., Scheynius A., Gudmundsson G.H.: Antimicrobial peptide LL-37internalized by immature human dendritic cells alters their phenotype.Scand. J. Immunol., 2006; 63: 410-419
    Google Scholar
  • 5. Barlow P.G., Li Y., Wilkinson T.S., Bowdish D.M., Lau Y.E., CosseauC., Haslett C., Simpson A.J., Hancock R.E., Davidson D.J.: The humancationic host defense peptide LL-37 mediates contrasting effects onapoptotic pathways in different primary cells of the innate immunesystem. J. Leukoc. Biol., 2006; 80: 509-520
    Google Scholar
  • 6. Bąbolewska E., Brzezińska-Błaszczyk E.: Human-derived cathelicidinLL-37 directly activates mast cells to proinflammatory mediatorsynthesis and migratory response. Cell Immunol., 2015; 293: 67-73
    Google Scholar
  • 7. Bąbolewska E., Pietrzak A., Brzezińska-Błaszczyk E.: CathelicidinrCRAMP stimulates rat mast cells to generate cysteinyl leukotrienes,synthesize TNF and migrate: involvement of PLC/A2, PI3K and MAPKsignaling pathways. Int. Immunol., 2014; 26: 637-646
    Google Scholar
  • 8. Befus A.D., Mowat C., Gilchrist M., Hu J., Solomon S., Bateman A.:Neutrophil defensins induce histamine secretion from mast cells:mechanisms of action. J. Immunol., 1999; 163: 947-953
    Google Scholar
  • 9. Biragyn A., Ruffini P.A., Leifer C.A., Klyushnenkova E., ShakhovA., Chertov O., Shirakawa A.K., Farber J.M., Segal D.M., OppenheimJ.J., Kwak L.W.: Toll-like receptor 4-dependent activation of dendriticcells by β-defensin 2. Science, 2002; 298: 1025-1029
    Google Scholar
  • 10. Biragyn A., Surenhu M., Yang D., Ruffini P.A., Haines B.A., KlyushnenkovaE., Oppenheim J.J., Kwak L.W.: Mediators of innate immunitythat target immature, but not mature, dendritic cells induceantitumor immunity when genetically fused with nonimmunogenictumor antigens. J. Immunol., 2001; 167: 6644-6653
    Google Scholar
  • 11. Bowdish D.M., Davidson D.J., Speert D.P., Hancock R.E.: The humancationic peptide LL-37 induces activation of the extracellularsignal-regulated kinase and p38 kinase pathways in primary humanmonocytes. J. Immunol., 2004; 172: 3758-3765
    Google Scholar
  • 12. Braff M.H., Hawkins M.A., Di Nardo A., Lopez-Garcia B., HowellM.D., Wong C., Lin K., Streib J.E., Dorschner R., Leung D.Y., Gallo R.L.:Structure-function relationships among human cathelicidin peptides:dissociation of antimicrobial properties from host immunostimulatoryactivities. J. Immunol., 2005; 174: 4271-4278
    Google Scholar
  • 13. Brogden K.A., Heidari M., Sacco R.E., Palmquist D., GuthmillerJ.M., Johnson G.K., Jia H.P., Tack B.F., McCray P.B.: Defensin-inducedadaptive immunity in mice and its potential in preventing periodontaldisease. Oral Microbiol. Immunol., 2003; 18: 95-99
    Google Scholar
  • 14. Brown M.G., McAlpine S.M., Huang Y.Y., Haidl I.D., Al-Afif A.,Marshall J.S., Anderson R.: RNA sensors enable human mast cellanti-viral chemokine production and IFN-mediated protection inresponse to antibody-enhanced dengue virus infection. PLoS One,2012; 7: e34055
    Google Scholar
  • 15. Brzezińska-Błaszczyk E., Wierzbicki M.: Mast cell Toll-like receptors(TLRs). Postępy Hig. Med. Dośw. 2010; 64: 11-21
    Google Scholar
  • 16. Chaly Y.V., Paleolog E.M., Kolesnikova T.S., Tikhonov I.I., PetratchenkoE.V., Voitenok N.N.: Neutrophil α-defensin human neutrophilpeptide modulates cytokine production in human monocytes andadhesion molecule expression in endothelial cells. Eur. CytokineNetw., 2000; 11: 257-266
    Google Scholar
  • 17. Chen X., Niyonsaba F., Ushio H., Hara M., Yokoi H., MatsumotoK., Saito H., Nagaoka I., Ikeda S., Okumura K., Ogawa H.: Antimicrobialpeptides human β-defensin (hBD)-3 and hBD-4 activate mastcells and increase skin vascular permeability. Eur. J. Immunol., 2007;37: 434-444
    Google Scholar
  • 18. Choi K.Y., Chow L.N., Mookherjee N.: Cationic host defence peptides:multifaceted role in immune modulation and inflammation.J. Innate Immun., 2012; 4: 361-370
    Google Scholar
  • 19. Choi K.Y., Napper S., Mookherjee N.: Human cathelicidin LL-37and its derivative IG-19 regulate interleukin-32-induced inflammation.Immunology, 2014; 143: 68-80
    Google Scholar
  • 20. Coffelt S.B., Tomchuck S.L., Zwezdaryk K.J., Danka E.S., ScandurroA.B.: Leucine leucine-37 uses formyl peptide receptor-like 1to activate signal transduction pathways, stimulate oncogenic geneexpression, and enhance the invasiveness of ovarian cancer cells.Mol. Cancer Res., 2009; 7: 907-915
    Google Scholar
  • 21. Davidson D.J., Currie A.J., Reid G.S., Bowdish D.M., MacDonaldK.L., Ma R.C., Hancock R.E., Speert D.P.: The cationic antimicrobialpeptide LL-37 modulates dendritic cell differentiation and dendriticcell-induced T cell polarization. J. Immunol., 2004; 172: 1146-1156
    Google Scholar
  • 22. Dawicki W., Marshall J.S.: New and emerging roles for mast cellsin host defence. Curr. Opin. Immunol., 2007; 19: 31-38
    Google Scholar
  • 23. De Yang B., Chen Q., Schmidt A.P., Anderson G.M., Wang J.M.,Wooters J., Oppenheim J.J., Chertov O.: LL-37, the neutrophil granule– and epithelial cell-derived cathelicidin, utilizes formyl peptidereceptor-like 1 (FPRL1) as a receptor to chemoattract humanperipheral blood neutrophils, monocytes, and T cells. J. Exp. Med.,2000; 192: 1069-1074
    Google Scholar
  • 24. Di Nardo A., Braff M.H., Taylor K.R., Na C., Granstein R.D., McInturffJ.E., Krutzik S., Modlin R.L., Gallo R.L.: Cathelicidin antimicrobialpeptides block dendritic cell TLR4 activation and allergic contactsensitization. J. Immunol., 2007; 178: 1829-1834
    Google Scholar
  • 25. Dimitriadou V., Mécheri S., Koutsilieris M., Fraser W., Al-DaccakR., Mourad W.: Expression of functional major histocompatibilitycomplex class II molecules on HMC-1 human mast cells. J. Leukoc.Biol., 1998; 64: 791-799
    Google Scholar
  • 26. Dosler S., Karaaslan E.: Inhibition and destruction of Pseudomonasaeruginosa biofilms by antibiotics and antimicrobial peptides.Peptides, 2014; 62: 32-37
    Google Scholar
  • 27. Elssner A., Duncan M., Gavrilin M., Wewers M.D.: A novel P2X7receptor activator, the human cathelicidin-derived peptide LL37, inducesIL-1β processing and release. J. Immunol., 2004; 172: 4987-4994
    Google Scholar
  • 28. Enoksson M., Ejendal K.F., McAlpine S., Nilsson G., LunderiusAnderssonC.: Human cord blood-derived mast cells are activatedby the Nod1 agonist M-TriDAP to release pro-inflammatory cytokinesand chemokines. J. Innate Immun., 2011; 3: 142-149
    Google Scholar
  • 29. Ericksen B., Wu Z., Lu W., Lehrer R.I.: Antibacterial activity andspecificity of the six human α-defensins. Antimicrob. Agents Chemother.,2005; 49: 269-275
    Google Scholar
  • 30. Feng B.S., Zheng P.Y., Chen X., Liao X.Q., Yang P.C.: Investigationof the role of cholera toxin in assisting the initiation of the antigenspecificTh2 response. Immunol. Invest., 2008; 37: 782-797
    Google Scholar
  • 31. Filewod N.C., Pistolic J., Hancock R.E.: Low concentrations of LL- 37 alter IL-8 production by keratinocytes and bronchial epithelialcells in response to proinflammatory stimuli. FEMS Immunol. Med. Microbiol., 2009; 56: 233-240
    Google Scholar
  • 32. Franchini M., Montagnana M.: Low-density lipoprotein receptorrelatedprotein 1: new functions for an old molecule. Clin. Chem.Lab. Med., 2011; 49: 967-970
    Google Scholar
  • 33. Fukuda M., Ushio H., Kawasaki J., Niyonsaba F., Takeuchi M.,Baba T., Hiramatsu K., Okumura K., Ogawa H.: Expression and functionalcharacterization of retinoic acid-inducible gene-I-like receptorsof mast cells in response to viral infection. J. Innate Immun.,2013; 5: 163-173
    Google Scholar
  • 34. Funderburg N., Lederman M.M., Feng Z., Drage M.G., JadlowskyJ., Harding C.V., Weinberg A., Sieg S.F.: Human β-defensin-3 activatesprofessional antigen-presenting cells via Toll-like receptors 1 and 2.Proc. Natl. Acad. Sci. USA, 2007; 104: 18631-18635
    Google Scholar
  • 35. Galli S.J., Grimbaldeston M., Tsai M.: Immunomodulatory mastcells: negative, as well as positive, regulators of immunity. Nat. Rev.Immunol., 2008; 8: 478-486
    Google Scholar
  • 36. Geijtenbeek T.B., Gringhuis S.I.: Signalling through C-type lectinreceptors: shaping immune responses. Nat. Rev. Immunol., 2009;9: 465-479
    Google Scholar
  • 37. Girnita A., Zheng H., Grönberg A., Girnita L., Ståhle M.: Identificationof the cathelicidin peptide LL-37 as agonist for the typeI insulin-like growth factor receptor. Oncogene, 2012; 31: 352-365
    Google Scholar
  • 38. Grigat J., Soruri A., Forssmann U., Riggert J., Zwirner J.: Chemoattractionof macrophages, T lymphocytes, and mast cells is evolutionarilyconserved within the human α-defensin family. J. Immunol.,2007; 179: 3958-3965
    Google Scholar
  • 39. Groeneveld T.W., Ramwadhdoebé T.H., Trouw L.A., van den HamD.L., van der Borden V., Drijfhout J.W., Hiemstra P.S., Daha M.R.,Roos A.: Human neutrophil peptide-1 inhibits both the classicaland the lectin pathway of complement activation. Mol. Immunol.,2007; 44: 3608-3614
    Google Scholar
  • 40. Haidl I.D., McAlpine S.M., Marshall J.S.: Enhancement of mastcell IL-6 production by combined toll-like and nucleotide-bindingoligomerization domain-like receptor activation. Int. Arch. AllergyImmunol., 2011; 154: 227-235
    Google Scholar
  • 41. Huang H.J., Ross C.R., Blecha F.: Chemoattractant propertiesof PR-39, a neutrophil antibacterial peptide. J. Leukoc. Biol., 1997;61: 624-629
    Google Scholar
  • 42. Ichinose M., Asai M., Imai K., Sawada M.: Enhancement of phagocytosisby corticostatin I (CSI) in cultured mouse peritoneal macrophages.Immunopharmacology, 1996; 35: 103-109
    Google Scholar
  • 43. Inohara N., Chamaillard M., McDonald C., Nuñez G.: NOD-LRRproteins: role in host-microbial interactions and inflammatory disease.Annu. Rev. Biochem., 2005; 74: 355-383
    Google Scholar
  • 44. Ito T., Tanabe H., Ayabe T., Ishikawa C., Inaba Y., Maemoto A.,Kono T., Ashida T., Fujiya M., Kohgo Y.: Paneth cells regulate bothchemotaxis of immature dendritic cells and cytokine productionfrom epithelial cells. Tohoku J. Exp. Med., 2012; 227: 39-48
    Google Scholar
  • 45. Jabłońska A., Paradowska E.: Rola receptorów RIG-I-podobnychw odpowiedzi przeciwwirusowej. Postępy Hig. Med. Dośw., 2014;68: 541-556
    Google Scholar
  • 46. Jarczak J., Kościuczuk E.M., Lisowski P., Strzałkowska N., JóźwikA., Horbańczuk J., Krzyżewski J., Zwierzchowski L., Bagnicka E.: Defensins:natural component of human innate immunity. Hum. Immunol.,2013; 74: 1069-1079
    Google Scholar
  • 47. Joly S., Maze C., McCray P.B.Jr, Guthmiller J.M.: Humanβ-defensins 2 and 3 demonstrate strain-selective activity againstoral microorganisms. J. Clin. Microbiol., 2004; 42: 1024-1029
    Google Scholar
  • 48. Kandler K., Shaykhiev R., Kleemann P., Klescz F., Lohoff M., VogelmeierC., Bals R.: The anti-microbial peptide LL-37 inhibits theactivation of dendritic cells by TLR ligands. Int. Immunol., 2006;18: 1729-1736
    Google Scholar
  • 49. Kase K., Hua J., Yokoi H., Ikeda K., Nagaoka I.: Inhibitory actionof roxithromycin on histamine release and prostaglandin D2 productionfrom β-defensin 2-stimulated mast cells. Int. J. Mol. Med.,2009; 23: 337-340
    Google Scholar
  • 50. Kim C., Gajendran N., Mittrücker H.W., Weiwad M., Song Y.H.,Hurwitz R., Wilmanns M., Fischer G., Kaufmann S.H.: Humanα-defensins neutralize anthrax lethal toxin and protect against itsfatal consequences. Proc. Natl. Acad. Sci. USA, 2005; 102: 4830-4835
    Google Scholar
  • 51. Kin N.W., Chen Y., Stefanov E.K., Gallo R.L., Kearney J.F.: Cathelin–related antimicrobial peptide differentially regulates T – and B-cellfunction. Eur. J. Immunol., 2011; 41: 3006-3016
    Google Scholar
  • 52. Kinet J.P.: The essential role of mast cells in orchestrating inflammation.Immunol. Rev., 2007; 217: 5-7
    Google Scholar
  • 53. Koczulla R., von Degenfeld G., Kupatt C., Krötz F., Zahler S., GloeT., Issbrücker K., Unterberger P., Zaiou M., Lebherz C., Karl A., RaakeP., Pfosser A., Boekstegers P., Welsch U. i wsp.: An angiogenic rolefor the human peptide antibiotic LL-37/hCAP-18. J. Clin. Invest.,2003; 111: 1665-1672
    Google Scholar
  • 54. Kościuczuk E.M., Lisowski P., Jarczak J., Strzałkowska N., Jóź-wik A., Horbańczuk J., Krzyżewski J., Zwierzchowski L., Bagnicka E.:Cathelicidins: family of antimicrobial peptides. A review. Mol. Biol.Rep., 2012; 39: 10957-10970
    Google Scholar
  • 55. Kurosaka K., Chen Q., Yarovinsky F., Oppenheim J.J. Yang D.:Mouse cathelin-related antimicrobial peptide chemoattracts leukocytesusing formyl peptide receptor-like 1/mouse formyl peptidereceptor-like 2 as the receptor and acts as an immune adjuvant. J.Immunol., 2005; 174: 6257-6265
    Google Scholar
  • 56. Lee J.K., Chang S.W., Perinpanayagam H., Lim S.M., Park Y.J., HanS.H., Baek S.H., Zhu Q., Bae K.S., Kum K.Y.: Antibacterial efficacy ofa human β-defensin-3 peptide on multispecies biofilms. J. Endod.,2013; 39: 1625-1629
    Google Scholar
  • 57. Machado L.R., Ottolini B.: An evolutionary history of defensins:a role for copy number variation in maximizing host innate and adaptiveimmune responses. Front. Immunol., 2015; 6: 115
    Google Scholar
  • 58. Malaviya R., Twesten N.J., Ross E.A., Abraham S.N., Pfeifer J.D.:Mast cells process bacterial Ags through a phagocytic route for classI MHC presentation to T cells. J. Immunol., 1996; 156: 1490-1496
    Google Scholar
  • 59. Montreekachon P., Chotjumlong P., Bolscher J.G., Nazmi K., ReutrakulV., Krisanaprakornkit S.: Involvement of P2X7 purinergic receptorand MEK1/2 in interleukin-8 up-regulation by LL-37 in humangingival fibroblasts. J. Periodontal. Res., 2011; 46: 327-337
    Google Scholar
  • 60. Mookherjee N., Brown K.L., Bowdish D.M., Doria S., Falsafi R.,Hokamp K., Roche F.M., Mu R., Doho G.H., Pistolic J., Powers J.P., BryanJ., Brinkman F.S., Hancock R.E.: Modulation of the TLR-mediatedinflammatory response by the endogenous human host defensepeptide LL-37. J. Immunol., 2006; 176: 2455-2464
    Google Scholar
  • 61. Mookherjee N., Hamill P., Gardy J., Blimkie D., Falsafi R., ChikatamarlaA., Arenillas D.J., Doria S., Kollmann T.R., Hancock R.E.:Systems biology evaluation of immune responses induced by humanhost defence peptide LL-37 in mononuclear cells. Mol. Biosyst.,2009; 5: 483-496
    Google Scholar
  • 62. Nagaoka I., Niyonsaba F., Tsutsumi-Ishii Y., Tamura H., HirataM.: Evaluation of the effect of human β-defensins on neutrophilapoptosis. Int. Immunol., 2008; 20: 543-553
    Google Scholar
  • 63. Nagaoka I., Tamura H., Hirata M.: An antimicrobial cathelicidinpeptide, human CAP18/LL-37, suppresses neutrophil apoptosis viathe activation of formyl-peptide receptor-like 1 and P2X7. J. Immunol.,2006; 176: 3044-3052
    Google Scholar
  • 64. Nieto-Patlán A., Campillo-Navarro M., Rodríguez-Cortés O.,Muñoz-Cruz S., Wong-Baeza I., Estrada-Parra S., Estrada-García I.,Serafín-López J., Chacón-Salinas R.: Recognition of Candida albicansby Dectin-1 induces mast cell activation. Immunobiology, 2015;220: 1093-1100
    Google Scholar
  • 65. Nijnik A., Pistolic J., Wyatt A., Tam S., Hancock R.E.: Human cathelicidinpeptide LL-37 modulates the effects of IFN-γ on APCs. J.Immunol., 2009; 183: 5788-5798
    Google Scholar
  • 66. Niyonsaba F., Iwabuchi K., Matsuda H., Ogawa H., Nagaoka I.:Epithelial cell-derived human β-defensin-2 acts as a chemotaxin formast cells through a pertussis toxin-sensitive and phospholipase C–dependent pathway. Int. Immunol., 2002; 14: 421-426
    Google Scholar
  • 67. Niyonsaba F., Iwabuchi K., Someya A., Hirata M., Matsuda H.Ogawa H. Nagaoka I.: A cathelicidin family of human antibacterialpeptide LL-37 induces mast cell chemotaxis. Immunology, 2002;106: 20-26
    Google Scholar
  • 68. Niyonsaba F., Someya A., Hirata M., Ogawa H., Nagaoka I.: Evaluationof the effects of peptide antibiotics human β-defensins-1/-2and LL-37 on histamine release and prostaglandin D2 productionfrom mast cells. Eur. J. Immunol., 2001; 31: 1066-1075
    Google Scholar
  • 69. Niyonsaba F., Ushio H., Hara M., Yokoi H., Tominaga M., TakamoriK., Kajiwara N., Saito H., Nagaoka I., Ogawa H., Okumura K.: Antimicrobialpeptides human β-defensins and cathelicidin LL-37 inducethe secretion of a pruritogenic cytokine IL-31 by human mast cells.J. Immunol., 2010; 184: 3526-3534
    Google Scholar
  • 70. Niyonsaba F., Ushio H., Nagaoka I., Okumura K., Ogawa H.: Thehuman β-defensins (-1, – 2, – 3, – 4) and cathelicidin LL-37 induceIL-18 secretion through p38 and ERK MAPK activation in primaryhuman keratinocytes. J. Immunol., 2005; 175: 1776-1784
    Google Scholar
  • 71. Niyonsaba F., Ushio H., Nakano N., Ng W., Sayama K., HashimotoK., Nagaoka I., Okumura K., Ogawa H.: Antimicrobial peptides humanβ-defensins stimulate epidermal keratinocyte migration, proliferationand production of proinflammatory cytokines and chemokines.J. Invest. Dermatol., 2007; 127: 594-604
    Google Scholar
  • 72. Okumura S., Yuki K., Kobayashi R., Okamura S., Ohmori K., SaitoH., Ra C., Okayama Y.: Hyperexpression of NOD2 in intestinal mastcells of Crohn›s disease patients: preferential expression of inflammatorycell-recruiting molecules via NOD2 in mast cells. Clin. Immunol.,2009; 130: 175-185
    Google Scholar
  • 73. Olynych T.J., Jakeman D.L., Marshall J.S.: Fungal zymosan inducesleukotriene production by human mast cells through a dectin-1-dependentmechanism. J. Allergy Clin. Immunol., 2006; 118: 837-843
    Google Scholar
  • 74. Petrov V., Funderburg N., Weinberg A., Sieg S.: Human β defensin-3induces chemokines from monocytes and macrophages:diminished activity in cells from HIV-infected persons. Immunology,2013; 140: 413-420
    Google Scholar
  • 75. Pérez-Cañadillas J.M., Zaballos A., Gutiérrez J., Varona R., RoncalF., Albar J.P., Márquez G., Bruix M.: NMR solution structure ofmurine CCL20/MIP-3α, a chemokine that specifically chemoattractsimmature dendritic cells and lymphocytes through its highly specificinteraction with the β-chemokine receptor CCR6. J. Biol. Chem.,2001; 276: 28372-28379
    Google Scholar
  • 76. Pistolic J., Cosseau C., Li Y., Yu J.J., Filewod N.C., Gellatly S.,Rehaume L.M., Bowdish D.M., Hancock R.E.: Host defence peptideLL-37 induces IL-6 expression in human bronchial epithelial cellsby activation of the NF-кB signaling pathway. J. Innate. Immun.,2009; 1: 254-267
    Google Scholar
  • 77. Quinn K.L., Henriques M., Tabuchi A., Han B., Yang H., ChengW.E., Tole S., Yu H., Luo A., Charbonney E., Tullis E., Lazarus A., RobinsonL.A., Ni H., Peterson B.R. i wsp.: Human neutrophil peptidesmediate endothelial-monocyte interaction, foam cell formation,and platelet activation. Arterioscler. Thromb. Vasc. Biol., 2011; 31:2070-2079
    Google Scholar
  • 78. Ribbing C., Engblom C., Lappalainen J., Lindstedt K., KovanenP.T., Karlsson M.A., Lundeberg L., Johansson C., Nilsson G., LunderiusAnderssonC., Scheynius A.: Mast cells generated from patients withatopic eczema have enhanced levels of granule mediators and animpaired Dectin-1 expression. Allergy, 2011; 66: 110-119
    Google Scholar
  • 79. Rodríguez-García M., Climent N., Oliva H., Casanova V., Franco R., Leon A., Gatell J.M., García F., Gallart T.: Increased α-defensins1-3 production by dendritic cells in HIV-infected individuals is associatedwith slower disease progression. PLoS One, 2010; 5: e9436
    Google Scholar
  • 80. Rosenfeld Y., Papo N., Shai Y.: Endotoxin (lipopolysaccharide)neutralization by innate immunity host-defense peptides. Peptideproperties and plausible modes of action. J. Biol. Chem., 2006; 281:1636-1643
    Google Scholar
  • 81. Röhrl J., Yang D., Oppenheim J.J., Hehlgans T.: Human β-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interactionwith CCR2. J. Immunol., 2010; 184: 6688-6694
    Google Scholar
  • 82. Sandig H., Bulfone-Paus S.: TLR signaling in mast cells: commonand unique features. Front. Immunol., 2012; 3: 185
    Google Scholar
  • 83. Schiemann F., Brandt E., Gross R., Lindner B., Mittelstädt J.,Sommerhoff C.P., Schulmistrat J., Petersen F.: The cathelicidin LL- 37 activates human mast cells and is degraded by mast cell tryptase:counter-regulation by CXCL4. J. Immunol., 2009; 183: 2223-2231
    Google Scholar
  • 84. Sharma S., Verma I., Khuller G.K.: Biochemical interaction of humanneutrophil peptide-1 with Mycobacterium tuberculosis H37Ra.Arch. Microbiol., 1999; 171: 338-342
    Google Scholar
  • 85. Shaykhiev R., Beisswenger C., Kändler K., Senske J. Püchner A.,Damm T., Behr J., Bals R.: Human endogenous antibiotic LL-37 stimulatesairway epithelial cell proliferation and wound closure. Am. J.Physiol. Lung Cell Mol. Physiol., 2005; 289: L842-L884
    Google Scholar
  • 86. Shaykhiev R., Sierigk J., Herr C., Krasteva G., Kummer W., Bals R.:The antimicrobial peptide cathelicidin enhances activation of lungepithelial cells by LPS. FASEB J., 2010; 24: 4756-4766
    Google Scholar
  • 87. Smithrithee R., Niyonsaba F., Kiatsurayanon C., Ushio H., IkedaS., Okumura K., Ogawa H.: Human β-defensin-3 increases the expressionof interleukin-37 through CCR6 in human keratinocytes.J. Dermatol. Sci., 2015; 77: 46-53
    Google Scholar
  • 88. Soehnlein O., Kai-Larsen Y., Frithiof R., Sorensen O.E., Kenne E.,Scharffetter-Kochanek K., Eriksson E.E., Herwald H., Agerberth B.,Lindbom L.: Neutrophil primary granule proteins HBP and HNP1-3boost bacterial phagocytosis by human and murine macrophages.J. Clin. Invest., 2008; 118: 3491-3502
    Google Scholar
  • 89. Soruri A., Grigat J., Forssmann U., Riggert J., Zwirner J.:β-defensins chemoattract macrophages and mast cells but not lymphocytesand dendritic cells: CCR6 is not involved. Eur. J. Immunol.,2007; 37: 2474-2486
    Google Scholar
  • 90. Subramanian H., Gupta K., Guo Q., Price R., Ali H.: Mas-relatedgene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobialpeptide LL-37 in human mast cells: resistance to receptorphosphorylation, desensitization, and internalization. J. Biol. Chem.,2011; 286: 44739-44749
    Google Scholar
  • 91. Subramanian H., Gupta K., Lee D., Bayir A.K., Ahn H., Ali H.:β-defensins activate human mast cells via Mas-related gene X2. J.Immunol., 2013; 191: 345-352
    Google Scholar
  • 92. Sun J., Dahlén B., Agerberth B., Haeggström J.Z.: The antimicrobialpeptide LL-37 induces synthesis and release of cysteinylleukotrienes from human eosinophils-implications for asthma. Allergy,2013; 68: 304-311
    Google Scholar
  • 93. Takeuchi O., Akira S.: Innate immunity to virus infection. Immunol.Rev., 2009; 227: 75-86
    Google Scholar
  • 94. Tani K., Murphy W.J., Chertov O., Salcedo R., Koh C.Y., UtsunomiyaI., Funakoshi S., Asai O., Herrmann S.H., Wang J.M., Kwak L.W., OppenheimJ.J.: Defensins act as potent adjuvants that promote cellularand humoral immune responses in mice to a lymphoma idiotype andcarrier antigens. Int. Immunol., 2000; 12: 691-700
    Google Scholar
  • 95. Tjabringa G.S., Aarbiou J., Ninaber D.K., Drijfhout J.W., SørensenO.E., Borregaard N., Rabe K.F., Hiemstra P.S.: The antimicrobial peptideLL-37 activates innate immunity at the airway epithelial surfaceby transactivation of the epidermal growth factor receptor. J. Immunol.,2003; 171: 6690-6696
    Google Scholar
  • 96. Tjabringa G.S., Ninaber D.K., Drijfhout J.W., Rabe K.F., HiemstraP.S.: Human cathelicidin LL-37 is a chemoattractant for eosinophilsand neutrophils that acts via formyl-peptide receptors. Int. Arch.Allergy Immunol., 2006; 140: 103-112
    Google Scholar
  • 97. Tokumaru S., Sayama K., Shirakata Y., Komatsuzawa H., OuharaK., Hanakawa Y., Yahata Y., Dai X., Tohyama M., Nagai H., Yang L.,Higashiyama S., Yoshimura A., Sugai M., Hashimoto K.: Induction ofkeratinocyte migration via transactivation of the epidermal growthfactor receptor by the antimicrobial peptide LL-37. J. Immunol.,2005; 175: 4662-4668
    Google Scholar
  • 98. Tomasinsig L., Pizzirani C., Skerlavaj B., Pellegatti P., GulinelliS., Tossi A., Di Virgilio F., Zanetti M.: The human cathelicidin LL-37modulates the activities of the P2X7 receptor in a structure-dependentmanner. J. Biol. Chem., 2008; 283: 30471-30481
    Google Scholar
  • 99. Tripathi S., Verma A., Kim E.J., White M.R., Hartshorn K.L.: LL- 37 modulates human neutrophil responses to influenza A virus. J.Leukoc. Biol., 2014; 96: 931-938
    Google Scholar
  • 100. Tsai M., Grimbaldeston M., Galli S.J.: Mast cells and immunoregulation/immunomodulation.Adv. Exp. Med. Biol., 2011; 716: 186-211
    Google Scholar
  • 101. van den Berg R.H., Faber-Krol M.C., van Wetering S., HiemstraP.S., Daha M.R.: Inhibition of activation of the classical pathwayof complement by human neutrophil defensins. Blood, 1998; 92:3898-3903
    Google Scholar
  • 102. Van Wetering S., Mannesse-Lazeroms S.P., Van SterkenburgM.A., Daha M.R., Dijkman J.H., Hiemstra P.S.: Effect of defensins oninterleukin-8 synthesis in airway epithelial cells. Am. J. Physiol.,1997; 272: L888-L896
    Google Scholar
  • 103. Vandamme D., Landuyt B., Luyten W., Schoofs L.: A comprehensivesummary of LL-37, the factotum human cathelicidin peptide.Cell Immunol., 2012; 280: 22-35
    Google Scholar
  • 104. Verbanac D., Zanetti M., Romeo D.: Chemotactic and proteaseinhibitingactivities of antibiotic peptide precursors. FEBS Lett.,1993; 317: 255-258
    Google Scholar
  • 105. Von Köckritz-Blickwede M., Goldmann O., Thulin P., HeinemannK., Norrby-Teglund A., Rohde M., Medina E.: Phagocytosis-independentantimicrobial activity of mast cells by means of extracellulartrap formation. Blood, 2008; 111: 3070-3080
    Google Scholar
  • 106. Wan M., Soehnlein O., Tang X., van der Does A.M., Smedler E.Uhlén P., Lindbom L., Agerberth B., Haeggström J.Z.: CathelicidinLL-37 induces time-resolved release of LTB4 and TXA2 by humanmacrophages and triggers eicosanoid generation in vivo. FASEB J.,2014; 28: 3456-3467
    Google Scholar
  • 107. Wantha S., Alard J.E., Megens R.T., van der Does A.M., DöringY., Drechsler M., Pham C.T., Wang M.W., Wang J.M., Gallo R.L., vonHundelshausen P., Lindbom L., Hackeng T., Weber C., Soehnlein O.:Neutrophil-derived cathelicidin promotes adhesion of classicalmonocytes. Circ. Res., 2013; 112: 792-801
    Google Scholar
  • 108. Wilson S.S., Wiens M.E., Smith J.G.: Antiviral mechanisms ofhuman defensins. J. Mol. Biol., 2013; 425: 4965-4980
    Google Scholar
  • 109. Witczak P., Brzezińska-Błaszczyk E.: Komórki tuczne w infekcjachwirusowych. Postępy Hig. Med. Dośw., 2012; 66: 231-241
    Google Scholar
  • 110. Witkowska D., Bartyś A., Gamian A.: Defensyny i katelicydynyjako naturalne antybiotyki peptydowe. Postępy Hig. Med. Dośw.,2008; 62: 694-707
    Google Scholar
  • 111. Wu L., Feng B.S., He S.H., Zheng P.Y., Croitoru K., Yang P.C.:Bacterial peptidoglycan breaks down intestinal tolerance via mastcell activation: the role of TLR2 and NOD2. Immunol. Cell Biol., 2007;85: 538-545
    Google Scholar
  • 112. Yang D., Chen Q., Chertov O., Oppenheim J.J.: Human neutrophildefensins selectively chemoattract naive T and immature dendriticcells. J. Leukoc. Biol., 2000; 68: 9-14
    Google Scholar
  • 113. Yang D., Chertov O., Bykovskaia S.N., Chen Q., Buffo M.J., ShoganJ., Anderson M., Schröder J.M., Wang J.M., Howard O.M., OppenheimJ.J.: β-defensins: linking innate and adaptive immunity through dendriticand T cell CCR6. Science, 286: 525-528
    Google Scholar
  • 114. Yang Z., Marshall J.S.: Zymosan treatment of mouse mast cellsenhances dectin-1 expression and induces dectin-1-dependent reactiveoxygen species (ROS) generation. Immunobiology, 2009; 214:321-330
    Google Scholar
  • 115. Yoshioka M., Fukuishi N., Kubo Y., Yamanobe H., Ohsaki K.,Kawasoe Y., Murata M., Ishizumi A., Nishii Y., Matsui N., Akagi M.:Human cathelicidin CAP18/LL-37 changes mast cell function towardinnate immunity. Biol. Pharm. Bull., 2008; 31: 212-216
    Google Scholar
  • 116. Yu J., Mookherjee N., Wee K., Bowdish D.M., Pistolic J., Li Y.,Rehaume L., Hancock R.E.: Host defense peptide LL-37, in synergywith inflammatory mediator IL-1β, augments immune responsesby multiple pathways. J. Immunol., 2007; 179: 7684-7691
    Google Scholar
  • 117. Zabucchi G., Trevisan E., Vita F., Soranzo M.R., Borelli V.: NOD1and NOD2 interact with the phagosome cargo in mast cells: a detailedmorphological evidence. Inflammation, 2015; 38: 1113-1125
    Google Scholar
  • 118. Zhang Z., Cherryholmes G., Chang F., Rose D.M., SchraufstatterI., Shively J.E.: Evidence that cathelicidin peptide LL-37 may act asa functional ligand for CXCR2 on human neutrophils. Eur. J. Immunol.,2009; 39: 3181-3194
    Google Scholar
  • 119. Zhang Z., Cherryholmes G., Shively J.E.: Neutrophil secondarynecrosis is induced by LL-37 derived from cathelicidin. J. Leukoc.Biol., 2008; 84: 780-788
    Google Scholar
  • 120. Zheng Y., Niyonsaba F., Ushio H., Nagaoka I., Ikeda S., OkumuraK., Ogawa H.: Cathelicidin LL-37 induces the generation of reactiveoxygen species and release of human α-defensins from neutrophils.Br. J. Dermatol., 2007; 157: 1124-1131
    Google Scholar

Full text

Skip to content