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CONCLUSION

Innate immunity is the first line of defense against pathogens. Leukocytes and mucosal epithelial cells are the main cells that produce defensins and play a major role in innate immune response.

Defensins display versatile functions in modulating various immunological and biological aspects. Aberrant defensin expression has been associated with many human diseases [151], although studies on the role of defensins in HIV pathogenesis and transmission in humans have just begun to reveal the complex functions of defensins in modulating HIV infection. While the innate immune system including defensins is evolutionary conserved among multicellular organisms, it is challenging to find a suitable animal model to study the role of defensins in HIV pathogenesis and transmission due to the complex diversity of defensins in mammals as well as apparent differences in mechanisms of action. Future studies focusing on the development of a better animal model for studying innate immunity in HIV transmission and pathogenesis as well as careful assessments of immune responses (soluble factors and immune cells) in patients with reduced or elevated levels of defensins will shed light on the development of novel therapeutics for HIV prevention.

REFERENCES

[1] Selsted ME, Ouellette AJ. Mammalian defensins in the antimicrobial immune response. Nat Immunol. 2005;6(6):551-557.

[2] Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003;3(9):710-720.

[3] Yang D, Biragyn A, Kwak LW, Oppenheim JJ. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 2002;23(6):291-296.

[4] Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 2004;22:181-215.

[5] Szyk A, Wu Z, Tucker K, Yang D, Lu W, Lubkowski J.

Crystal structures of human alpha-defensins HNP4, HD5, and HD6. Protein Sci. 2006;15(12):2749-2760.

[6] Pardi A, Zhang XL, Selsted ME, Skalicky JJ, Yip PF. NMR studies of defensin antimicrobial peptides. 2. Three­dimensional structures of rabbit NP-2 and human HNP-1. Biochemistry. 1992;31(46):11357-11364.

[7] Hill CP, Yee J, Selsted ME, Eisenberg D. Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991;251(5000):1481-1485.

[8] Hoover DM, Chertov O, Lubkowski J. The structure of human beta-defensin-1: new insights into structural properties of beta-defensins. J Biol Chem. 2001;276(42):39021-39026.

[9] Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, et al. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol. 2002;3(6):583-590.

[10] Porter E, Yang H, Yavagal S, Preza GC, Murillo O, Lima H, et al. Distinct defensin profiles in Neisseria gonorrhoeae and Chlamydia trachomatis urethritis reveal novel epithelial cell-neutrophil interactions. Infect Immun. 2005;73(8):4823-4833.

[11] Tang YQ, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science. 1999;286(5439):498-502.

[12] Leonova L, Kokryakov VN, Aleshina G, Hong T, Nguyen T, Zhao C, et al. Circular minidefensins and posttranslational generation of molecular diversity. J Leukoc Biol. 2001;70(3):461-464.

[13] Tran D, Tran PA, Tang YQ, Yuan J, Cole T, Selsted ME. Homodimeric theta-defensins from rhesus macaque leukocytes: isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J Biol Chem. 2002;277(5):3079-3084.

[14] Maemoto A, Qu X, Rosengren KJ, Tanabe H, Henschen-Edman A, Craik DJ, et al. Functional analysis of the alpha-defensin disulfide array in mouse cryptdin-4. J Biol Chem. 2004;279(42):44188-44196.

[15] Wu Z, Hoover DM, Yang D, Boulegue C, Santamaria F, Oppenheim JJ, et al.

Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc Natl Acad Sci USA. 2003;100(15):8880-8885.

[16] Mandal M, Nagaraj R. Antibacterial activities and conformations of synthetic alpha-defensin HNP-1 and analogs with one, two and three disulfide bridges. J Pept Res. 2002;59(3):95-104.

[17] Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986;60(3):1068-1074.

[18] Wang W, Cole AM, Hong T, Waring AJ, Lehrer RI. Retrocyclin, an antiretroviral theta-defensin, is a lectin. J Immunol. 2003;170(9):4708-4716.

[19] Klotman ME, Rapista A, Teleshova N, Micsenyi A, Jarvis GA, Lu W, et al. Neisseria gonorrhoeae-Induced Human Defensins 5 and 6 Increase HIV Infectivity: Role in Enhanced Transmission. J Immunol. 2008;180(9):6176-6185.

[20] Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, et al. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985;76(4):1427-1435.

[21] Selsted ME, Harwig SS, Ganz T, Schilling JW, Lehrer RI. Primary structures of three human neutrophil defensins. J Clin Invest. 1985;76(4):1436-1439.

[22] Wilde CG, Griffith JE, Marra MN, Snable JL, Scott RW. Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family. J Biol Chem. 1989;264(19):11200-11203.

[23] Rodriguez-Garcia M, Oliva H, Climent N, Garcia F, Gatell JM, Gallart T. Human immature monocyte-derived dendritic cells produce and secrete alpha-defensins 1-3. J Leukoc Biol. 2007;82(5):1143-1146.

[24] Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000;96(9):3086-3093.

[25] Ganz T. Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytes. Infect Immun. 1987;55(3):568-571.

[26] Mackewicz CE, Yuan J, Tran P, Diaz L, Mack E, Selsted ME, et al.

alpha-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS. 2003;17(14):F23-32.

[27] Zaharatos GJ, He T, Lopez P, Yu W, Yu J, Zhang L. alpha-Defensins Released Into Stimulated CD8+ T-Cell Supernatants Are Likely Derived From Residual Granulocytes Within the Irradiated Allogeneic Peripheral Blood Mononuclear Cells Used as Feeders. J Acquir Immune Defic Syndr. 2004;36(5):993-1005.

[28] Hein M, Valore EV, Helmig RB, Uldbjerg N, Ganz T. Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol. 2002;187(1):137-144.

[29] Fellermann K, Stange EF. Defensins -- innate immunity at the epithelial frontier. Eur J Gastroenterol Hepatol. 2001;13(7):771-776.

[30] Cunliffe RN. Alpha-defensins in the gastrointestinal tract. Mol Immunol. 2003;40(7):463-467.

[31] Simhan HN, Anderson BL, Krohn MA, Heine RP, Martinez de Tejada B, Landers DV, et al. Host immune consequences of asymptomatic Trichomonas vaginalis infection in pregnancy. Am J Obstet Gynecol. 2007;196(1):59 e51-55.

[32] Wiesenfeld HC, Heine RP, Krohn MA, Hillier SL, Amortegui AA, Nicolazzo M, et al. Association between elevated neutrophil defensin levels and endometritis. J Infect Dis. 2002;186(6):792-797.

[33] Valore EV, Wiley DJ, Ganz T. Reversible deficiency of antimicrobial polypeptides in bacterial vaginosis. Infect Immun. 2006;74(10):5693-5702.

[34] Heine RP, Wiesenfeld H, Mortimer L, Greig PC. Amniotic fluid defensins: potential markers of subclinical intrauterine infection. Clin Infect Dis. 1998;27(3):513-518.

[35] Salzman NH, Underwood MA, Bevins CL. Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol. 2007;19(2):70-83.

[36] Tanabe H, Yuan J, Zaragoza MM, Dandekar S, Henschen-Edman A, Selsted ME, et al. Paneth cell alpha-defensins from rhesus macaque small intestine. Infect Immun. 2004;72(3):1470-1478.

[37] Fahlgren A, Hammarstrom S, Danielsson A, Hammarstrom ML. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis.

Clin Exp Immunol. 2003;131(1):90-101.

[38] Svinarich DM, Wolf NA, Gomez R, Gonik B, Romero R. Detection of human defensin 5 in reproductive tissues. Am J Obstet Gynecol. 1997;176(2):470-475.

[39] Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, et al. Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol. 1998;152(5):1247-1258.

[40] Fan SR, Liu XP, Liao QP. Human defensins and cytokines in vaginal lavage fluid of women with bacterial vaginosis. Int J Gynaecol Obstet. 2008.

[41] Yamaguchi Y, Nagase T, Makita R, Fukuhara S, Tomita T, Tominaga T, et al. Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice. J Immunol. 2002;169(5):2516-2523.

[42] Pazgier M, Hoover DM, Yang D, Lu W, Lubkowski J. Human beta-defensins. Cell Mol Life Sci. 2006;63(11):1294-1313.

[43] Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, et al. Discovery of five conserved beta - defensin gene clusters using a computational search strategy. Proc Natl Acad Sci USA. 2002;99(4):2129-2133.

[44] Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH. Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology. 2002;106(4):517-525.

[45] Proud D, Sanders SP, Wiehler S. Human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo. J Immunol. 2004;172(7):4637-4645.

[46] Duits LA, Nibbering PH, van Strijen E, Vos JB, Mannesse-Lazeroms SP, van Sterkenburg MA, et al. Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells. FEMS Immunol Med Microbiol. 2003;38(1):59-64.

[47] Yang D, Chertov O, Oppenheim JJ. Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37). J Leukoc Biol. 2001;69(5):691-697.

[48] Sorensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T. Differential regulation of beta-defensin expression in human skin by microbial stimuli. J Immunol. 2005;174(8):4870-4879.

[49] Harder J, Bartels J, Christophers E, Schroder JM. Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem. 2001;276(8):5707-5713.

[50] Garcia JR, Jaumann F, Schulz S, Krause A, Rodriguez-Jimenez J, Forssmann U, et al. Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res. 2001;306(2):257-264.

[51] Armogida SA, Yannaras NM, Melton AL, Srivastava MD. Identification and quantification of innate immune system mediators in human breast milk. Allergy Asthma Proc. 2004;25(5):297-304.

[52] Jia HP, Starner T, Ackermann M, Kirby P, Tack BF, McCray PB, Jr. Abundant human beta-defensin-1 expression in milk and mammary gland epithelium. J Pediatr. 2001;138(1):109-112.

[53] Garcia JR, Krause A, Schulz S, Rodriguez-Jimenez FJ, Kluver E, Adermann K, et al. Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J. 2001;15(10):1819-1821.

[54] Nguyen TX, Cole AM, Lehrer RI. Evolution of primate theta-defensins: a serpentine path to a sweet tooth. Peptides. 2003;24(11):1647-1654.

[55] Cole AM, Hong T, Boo LM, Nguyen T, Zhao C, Bristol G, et al. Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci USA. 2002;99(4):1813-1818.

[56] Cowland JB, Borregaard N. The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granules. J Leukoc Biol. 1999;66(6):989-995.

[57] Tsutsumi-Ishii Y, Hasebe T, Nagaoka I. Role of CCAAT/enhancer-binding protein site in transcription of human neutrophil peptide-1 and -3 defensin genes. J Immunol. 2000;164(6):3264-3273.

[58] Joiner KA, Ganz T, Albert J, Rotrosen D. The opsonizing ligand on Salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes. J Cell Biol. 1989;109(6 Pt 1):2771-2782.

[59] Tanaka S, Edberg JC, Chatham W, Fassina G, Kimberly RP. Fc gamma RIIIb allele-sensitive release of alpha- defensins: anti-neutrophil cytoplasmic antibody-induced release of chemotaxins. J Immunol. 2003;171(11):6090- 6096.

[60] Chalifour A, Jeannin P, Gauchat JF, Blaecke A, Malissard M, N'Guyen T, et al. Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood. 2004;104(6):1778- 1783.

[61] Jan MS, Huang YH, Shieh B, Teng RH, Yan YP, Lee YT, et al. CC Chemokines Induce Neutrophils to Chemotaxis, Degranulation, and alpha-Defensin Release. J Acquir Immune Defic Syndr. 2006;41(1):6-16.

[62] Driss V, Legrand F, Hermann E, Loiseau S, Guerardel Y, Kremer L, et al. TLR2-dependent eosinophil interactions with mycobacteria : role of {alpha}-defensins. Blood. 2009 Apr 2;113(14):3235-44.

[63] Cunliffe RN, Rose FR, Keyte J, Abberley L, Chan WC, Mahida YR. 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. 2001;48(2):176-185.

[64] George MD, Wehkamp J, Kays RJ, Leutenegger CM, Sabir S, Grishina I, et al. In vivo gene expression profiling of human intestinal epithelial cells: analysis by laser microdissection of formalin fixed tissues. BMC Genomics. 2008;9:209.

[65] Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M, et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004;53(11):1658-1664.

[66] Wehkamp J, Wang G, Kubler I, Nuding S, Gregorieff A, Schnabel A, et al. The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J Immunol. 2007;179(5):3109-3118.

[67] Hertz CJ, Wu Q, Porter EM, Zhang YJ, Weismuller KH, Godowski PJ, et al. Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J Immunol. 2003;171(12):6820-6826.

[68] Vora P, Youdim A, Thomas LS, Fukata M, Tesfay SY, Lukasek K, et al. Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J Immunol. 2004;173(9):5398-5405.

[69] Uehara A, Fujimoto Y, Fukase K, Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol. 2007;44(12):3100-3111.

[70] Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L. 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. 2005;124(5):931-938.

[71] Pivarcsi A, Nagy I, Koreck A, Kis K, Kenderessy-Szabo A, Szell M, et al. Microbial compounds induce the expression of pro-inflammatory cytokines, chemokines and human beta-defensin-2 in vaginal epithelial cells. Microbes Infect. 2005;7:1117-1127.

[72] Schaefer TM, Fahey JV, Wright JA, Wira CR. Innate immunity in the human female reproductive tract: antiviral response of uterine epithelial cells to the TLR3 agonist poly(I:C). J Immunol. 2005;174(2):992-1002.

[73] Quinones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, et al. Human epithelial beta- defensins 2 and 3 inhibit HIV-1 replication. AIDS. 2003;17(16):F39-48.

[74] Uehara A, Takada H. Synergism between TLRs and NOD1/2 in oral epithelial cells. J Dent Res. 2008;87(7):682-686.

[75] Huang F, Kao CY, Wachi S, Thai P, Ryu J, Wu R. Requirement for both JAK-mediated PI3K signaling and ACT1/TRAF6/TAK1-dependent NF-kappaB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells. J Immunol. 2007;179(10):6504-6513.

[76] Jang BC, Lim KJ, Suh MH, Park JG, Suh SI. Dexamethasone suppresses interleukin-1beta-induced human beta- defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells. FEMS Immunol Med Microbiol. 2007;51(1):171-184.

[77] Kao CY, Kim C, Huang F, Wu R. Requirements for two proximal NF-kappaB binding sites and IkappaB-zeta in IL-17A-induced human beta-defensin 2 expression by conducting airway epithelium. J Biol Chem. 2008;283(22):15309-15318.

[78] Lehrer RI, Lichtenstein AK, Ganz T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol. 1993;11:105-128.

[79] Bohling A, Hagge SO, Roes S, Podschun R, Sahly H, Harder J, et al. Lipid-specific membrane activity of human beta-defensin-3. Biochemistry. 2006;45(17):5663-5670.

[80] Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother. 2005;49(1):269-275.

[81] Sakamoto N, Mukae H, Fujii T, Ishii H, Yoshioka S, Kakugawa T, et al. Differential effects of alpha- and beta- defensin on cytokine production by cultured human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2005;288(3):L508-513.

[82] Rehaume LM, Hancock RE. Neutrophil-derived defensins as modulators of innate immune function. Crit Rev Immunol. 2008;28(3):185-200.

[83] Coffelt SB, Scandurro AB. Tumors sound the alarmin(s). Cancer Res. 2008;68(16):6482-6485.

[84] Liu HY, Collins QF, Moukdar F, Zhuo D, Han J, Hong T, et al. Suppression of hepatic glucose production by human neutrophil alpha-defensins through a signaling pathway distinct from insulin. J Biol Chem. 2008;283(18):12056-12063.

[85] Joseph G, Tarnow L, Astrup AS, Hansen TK, Parving HH, Flyvbjerg A, et al. Plasma alpha-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients. J Clin Endocrinol Metab. 2008;93(4):1470-1475.

[86] Saraheimo M, Forsblom C, Pettersson-Fernholm K, Flyvbjerg A, Groop PH, Frystyk J. Increased levels of alpha- defensin (-1, -2 and -3) in type 1 diabetic patients with nephropathy. Nephrol Dial Transplant. 2008;23(3):914-918.

[87] Kruse T, Kristensen HH. Using antimicrobial host defense peptides as anti-infective and immunomodulatory agents. Expert Rev Anti Infect Ther. 2008;6(6):887-895.

[88] Yang D, Chen Q, Chertov O, Oppenheim JJ. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol. 2000;68(1):9-14.

[89] Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, et al. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem. 1996;271(6):2935-2940.

[90] Tecle T, White MR, Gantz D, Crouch EC, Hartshorn KL. Human neutrophil defensins increase neutrophil uptake of influenza A virus and bacteria and modify virus-induced respiratory burst responses. J Immunol. 2007;178(12):8046-8052.

[91] Shi J, Aono S, Lu W, Ouellette AJ, Hu X, Ji Y, et al. A novel role for defensins in intestinal homeostasis: regulation of IL-1beta secretion. J Immunol. 2007;179(2):1245-1253.

[92] Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999;286(5439):525-528.

[93] Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000;12(2):121-127.

[94] Niyonsaba F, Hirata M, Ogawa H, Nagaoka I. Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells. Curr Drug Targets Inflamm Allergy. 2003;2(3):224-231.

[95] Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, et al. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science. 2002;298(5595):1025-1029.

[96] Funderburg N, Lederman MM, Feng Z, Drage MG, Jadlowsky J, Harding CV, et al. Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci USA. 2007;104(47):18631-18635.

[97] Klotman ME, Chang TL. Defensins in innate antiviral immunity. Nat Rev Immunol. 2006;6(6):447-456.

[98] Van Wetering S, Mannesse-Lazeroms SP, Van Sterkenburg MA, Daha MR, Dijkman JH, Hiemstra PS. Effect of defensins on interleukin-8 synthesis in airway epithelial cells. Am J Physiol. 1997;272(5 Pt 1):L888-896.

[99] Guo CJ, Tan N, Song L, Douglas SD, Ho WZ. Alpha-defensins inhibit HIV infection of macrophages through upregulation of CC-chemokines. Aids. 2004;18(8):1217-1218.

[100] Boniotto M, Jordan WJ, Eskdale J, Tossi A, Antcheva N, Crovella S, et al. Human beta-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells. Antimicrob Agents Chemother. 2006;50(4):1433-1441.

[101] Liu CY, Lin HC, Yu CT, Lin SM, Lee KY, Chen HC, et al. The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells. Life Sci. 2007;80(8):749-758.

[102] Narimatsu R, Wolday D, Patterson BK. IL-8 increases transmission of HIV type 1 in cervical explant tissue. AIDS Res Hum Retroviruses. 2005;21(3):228-233.

[103] Nassar T, Akkawi S, Bar-Shavit R, Haj-Yehia A, Bdeir K, Al-Mehdi AB, et al. Human alpha-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. Blood. 2002;100(12):4026-4032.

[104] Higazi AA, Nassar T, Ganz T, Rader DJ, Udassin R, Bdeir K, et al. The alpha-defensins stimulate proteoglycan­dependent catabolism of low-density lipoprotein by vascular cells: a new class of inflammatory apolipoprotein and a possible contributor to atherogenesis. Blood. 2000;96(4):1393-1398.

[105] Higazi AA, Ganz T, Kariko K, Cines DB. Defensin modulates tissue-type plasminogen activator and plasminogen binding to fibrin and endothelial cells. J Biol Chem. 1996;271(30):17650-17655.

[106] Charp PA, Rice WG, Raynor RL, Reimund E, Kinkade JM, Jr., Ganz T, et al. Inhibition of protein kinase C by defensins, antibiotic peptides from human neutrophils. Biochem Pharmacol. 1988;37(5):951-956.

[107] Chang TL, Vargas J, Jr., DelPortillo A, Klotman ME. Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest. 2005;115(3):765-773.

[108] Nakashima H, Yamamoto N, Masuda M, Fujii N. Defensins inhibit HIV replication in vitro. Aids. 1993;7(8):1129.

[109] Furci L, Sironi F, Tolazzi M, Vassena L, Lusso P. Alpha-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4. Blood. 2007;109(7):2928-2935.

[110] Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, et al. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science. 2002;298(5595):995-1000.

[111] Chang TL, Francois F, Mosoian A, Klotman ME. CAF-mediated human immunodeficiency virus (HIV) type 1 transcriptional inhibition is distinct from alpha-defensin-1 HIV inhibition. J Virol. 2003;77(12):6777-6784.

[112] Wu Z, Cocchi F, Gentles D, Ericksen B, Lubkowski J, Devico A, et al. Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett. 2005;579(1):162-166.

[113] Territo MC, Ganz T, Selsted ME, Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest. 1989;84(6):2017-2020.

[114] Wang W, Owen SM, Rudolph DL, Cole AM, Hong T, Waring AJ, et al. Activity of alpha- and theta-defensins against primary isolates of HIV-1. J Immunol. 2004;173(1):515-520.

[115] Okrent DG, Lichtenstein AK, Ganz T. Direct cytotoxicity of polymorphonuclear leukocyte granule proteins to human lung-derived cells and endothelial cells. Am Rev Respir Dis. 1990;141(1):179-185.

[116] Van Wetering S, Mannesse-Lazeroms SP, Dijkman JH, Hiemstra PS. Effect of neutrophil serine proteinases and defensins on lung epithelial cells: modulation of cytotoxicity and IL-8 production. J Leukoc Biol. 1997;62(2):217-226.

[117] Tanabe H, Ouellette AJ, Cocco MJ, Robinson WE, Jr. Differential effects on human immunodeficiency virus type 1 replication by alpha-defensins with comparable bactericidal activities. J Virol. 2004;78(21):11622-11631.

[118] Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P, La Terra Maggiore GM, et al. Human {beta}-Defensins Suppress Human Immunodeficiency Virus Infection: Potential Role in Mucosal Protection. J Virol. 2005;79(22):14318-14329.

[119] Munk C, Wei G, Yang OO, Waring AJ, Wang W, Hong T, et al. The theta-defensin, retrocyclin, inhibits HIV-1 entry. AIDS Res Hum Retroviruses. 2003;19(10):875-881.

[120] Wang SZ, Smith PK, Lovejoy M, Bowden JJ, Alpers JH, Forsyth KD. The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis. Clin Exp Immunol. 1998;114(1):49-54.

[121] Gallo SA, Wang W, Rawat SS, Jung G, Waring AJ, Cole AM, et al. Theta-defensins prevent HIV-1 Env-mediated fusion by binding gp41 and blocking 6-helix bundle formation. J Biol Chem. 2006;281(27):18787-18792.

[122] Owen SM, Rudolph DL, Wang W, Cole AM, Waring AJ, Lal RB, et al. RC-101, a retrocyclin-1 analogue with enhanced activity against primary HIV type 1 isolates. AIDS Res Hum Retroviruses. 2004;20(11):1157-1165.

[123] Panyutich AV, Szold O, Poon PH, Tseng Y, Ganz T. Identification of defensin binding to C1 complement. FEBS Lett. 1994;356(2-3):169-173.

[124] Panyutich A, Ganz T. Activated alpha 2-macroglobulin is a principal defensin-binding protein. Am J Respir Cell Mol Biol. 1991;5(2):101-106.

[125] Mukae H, Iiboshi H, Nakazato M, Hiratsuka T, Tokojima M, Abe K, et al. Raised plasma concentrations of alpha- defensins in patients with idiopathic pulmonary fibrosis. Thorax. 2002;57(7):623-628.

[126] Ihi T, Nakazato M, Mukae H, Matsukura S. Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin Infect Dis. 1997;25(5):1134-1140.

[127] Panyutich AV, Panyutich EA, Krapivin VA, Baturevich EA, Ganz T. Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis. J Lab Clin Med. 1993;122(2):202-207.

[128] Gardner MS, Rowland MD, Siu AY, Bundy JL, Wagener DK, Stephenson JL. Comprehensive defensin assay for saliva. Anal Chem. 2009;81(2):557-566.

[129] Levinson P, Kaul R, Kimani J, Ngugi E, Moses S, Macdonald KS, et al. Levels of innate immune factors in genital fluids: association of alpha defensins and LL-37 with genital infections and increased HIV acquisition. AIDS. 2008.

[130] Trabattoni D, Caputo SL, Maffeis G, Vichi F, Biasin M, Pierotti P, et al. Human alpha Defensin in HIV-Exposed But Uninfected Individuals. J Acquir Immune Defic Syndr. 2004;35(5):455-463.

[131] Kuhn L, Trabattoni D, Kankasa C, Semrau K, Kasonde P, Lissoni F, et al. Alpha-defensins in the prevention of HIV transmission among breastfed infants. J Acquir Immune Defic Syndr. 2005;39(2):138-142.

[132] Bosire R, John-Stewart GC, Mabuka JM, Wariua G, Gichuhi C, Wamalwa D, et al. Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission. AIDS Res Hum Retroviruses. 2007;23(2):198-203.

[133] Folkvord JM, Armon C, Connick E. Lymphoid follicles are sites of heightened human immunodeficiency virus type 1 (HIV-1) replication and reduced antiretroviral effector mechanisms. AIDS Res Hum Retroviruses. 2005;21(5):363-370.

[134] Venkataraman N, Cole AL, Svoboda P, Pohl J, Cole AM. Cationic polypeptides are required for anti-HIV-1 activity of human vaginal fluid. J Immunol. 2005;175(11):7560-7567.

[135] Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol. 2004;2(1):33-42.

[136] Plummer FA. Heterosexual transmission of human immunodeficiency virus type 1 (HIV): interactions of conventional sexually transmitted diseases, hormonal contraception and HIV-1. AIDS Res Hum Retroviruses. 1998;14 Suppl 1:S5-10.

[137] Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. Lancet. 1997;349(9069):1868-1873.

[138] Chesson HW, Pinkerton SD. Sexually transmitted diseases and the increased risk for HIV transmission: implications for cost-effectiveness analyses of sexually transmitted disease prevention interventions. J Acquir Immune Defic Syndr. 2000;24(1):48-56.

[139] Mabey D. Interactions between HIV infection and other sexually transmitted diseases. Trop Med Int Health. 2000;5(7):A32-36.

[140] Matsushita I, Hasegawa K, Nakata K, Yasuda K, Tokunaga K, Keicho N. Genetic variants of human beta-defensin- 1 and chronic obstructive pulmonary disease. Biochem Biophys Res Commun. 2002;291(1):17-22.

[141] Salvatore F, Scudiero O, Castaldo G. Genotype-phenotype correlation in cystic fibrosis: the role of modifier genes. Am J Med Genet. 2002;111(1):88-95.

[142] Vankeerberghen A, Scudiero O, De Boeck K, Macek M, Jr., Pignatti PF, Van Hul N, et al. Distribution of human beta-defensin polymorphisms in various control and cystic fibrosis populations. Genomics. 2005;85(5):574-581.

[143] Levy H, Raby BA, Lake S, Tantisira KG, Kwiatkowski D, Lazarus R, et al. Association of defensin beta-1 gene polymorphisms with asthma. J Allergy Clin Immunol. 2005;115(2):252-258.

[144] Dork T, Stuhrmann M. Polymorphisms of the human beta-defensin-1 gene. Mol Cell Probes. 1998;12(3):171-173.

[145] Braida L, Boniotto M, Pontillo A, Tovo PA, Amoroso A, Crovella S. A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated with HIV-1 infection in Italian children. AIDS. 2004;18(11):1598-1600.

[146] Milanese M, Segat L, Pontillo A, Arraes LC, de Lima Filho JL, Crovella S. DEFB1 gene polymorphisms and increased risk of HIV-1 infection in Brazilian children. Aids. 2006;20(12):1673-1675.

[147] Ricci E, Malacrida S, Zanchetta M, Montagna M, Giaquinto C, Rossi AD. Role of beta-Defensin-1 Polymorphisms in Mother-to-Child Transmission of Human Immunodeficiency Virus Type 1. J Acquir Immune Defic Syndr. 2009;51(1):13-9.

[148] Milanese M, Segat L, Crovella S. Transcriptional effect of DEFB1 gene 5' untranslated region polymorphisms. Cancer Res. 2007;67(12):5997; author reply 5997.

[149] Zapata W, Rodriguez B, Weber J, Estrada H, Quinones-Mateu ME, Zimermman PA, et al. Increased levels of human beta-defensins mRNA in sexually HIV-1 exposed but uninfected individuals. Curr HIV Res. 2008;6(6):531-538.

[150] Yang C, Boone L, Nguyen TX, Rudolph D, Limpakarnjanarat K, Mastro TD, et al. theta-Defensin pseudogenes in HIV-1-exposed, persistently seronegative female sex-workers from Thailand. Infect Genet Evol. 2005;5(1):11-15.

[151] de Leeuw E, Lu W. Human defensins: turning defense into offense? Infect Disord Drug Targets. 2007;7(1):67-70.

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Source: Alfano Massimo (ed.). Soluble Factors Mediating Innate Immune Responses to HIV Infection. Bentham Books,2010. — 159 p.. 2010
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