Research Progress on Human Defensin 5_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Guangkuo , SU Yongping.

The State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Combined Injury, The Third Military Medical University, Chongqing 400038, China;

Corresponding author：

Keywords：

Paneth cells; Human defensin 5; Enterogenic infection

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ObjectiveTo review the characteristics of human defensin 5 (HD-5), including molecular structure, antibacterial activity and gene expression, and to show its development prospect as a new drug in the treatment of enterogenic infection. MethodsThe published papers about HD-5 were reviewed to summarize its research progress. ResultsBeing a 3-5 KDa cationic peptide rich in cysteine and arginine, especially without glycosylated side-chain, HD-5 plays its antibacterial role against positive and negative Gram’s bacterium, fungi, spirochete, protozoan and enveloped virus with the special active center composed of three disulfide bonds. HD-5 encoding gene alpha defensin 5 (DEFA5) localizes at the 8th chromosome P21-pter with 449 bp, which includes five pieces of sequence: 5′ untranslated region (1-40)，signal peptide (41-97), propiece (98-226), mature peptide (227-322)，and Poly A (433-438).ConclusionAs a broad-spectrum and effective endogenous antimicrobial peptide, HD-5 would be a promising alternative peptide against enterogenic infection if the accessibility to its mass production is settled.

Citation： LI Guangkuo,SU Yongping.. Research Progress on Human Defensin 5. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2004, 11(4): 373-376. doi: Copy

1.	Ganz T, Selsted ME, Szklarek D, et al. Defensins. Natural peptide antibiotics of human neutrophils [J]. J Clin Invest, 1985; 76(4)∶1427.
2.	Rice WG, Ganz T, Kinkade JM Jr, et al. Defensinrich dense granules of human neutrophils [J]. Blood, 1987; 70(3)∶757.
3.	Lehrer RI, Ganz T, Selsted ME. Defensins: endogenous antibiotic peptides of animal cells [J]. Cell, 1991; 64(2)∶229.
4.	Ogata K, Linzer BA, Zuberi RI, et al. Activity of defensins from human neutrophilic granulocytes against Mycobacterium aviumMycobacterium intracellulare [J]. Infect Immun, 1992; 60(11)∶4720.
5.	Gabay JE, Almeida RP. Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin [J]. Curr Opin Immunol, 1993; 5(1)∶97.
6.	Jones DE, Bevins CL. Paneth cells of the human small intestine express an antimicrobial peptide gene [J]. J Biol Chem, 1992; 267(32)∶23216.
7.	Bevins CL, Jones DE, Dutra A, et al. Human enteric defensin genes: chromosomal map position and a model for possible evolutionary relationships [J]. Genomics, 1996; 31(1)∶95.
8.	Ghosh D, Porter E, Shen B, et al. Paneth cell trypsin is the processing enzyme for human defensin5 [J]. Nat Immunol, 2002; 3(6)∶583.
9.	Com E, Bourgeon F, Evrard B, et al. Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans [J]. Biol Reprod, 2003; 68(1)∶95.
10.	Porter EM, Poles MA, Lee JS, et al. Isolation of human intestinal defensins from ileal neobladder urine [J]. FEBS Lett, 1998; 434(3)∶272.
11.	Martin E, Ganz T, Lehrer RI. Defensins and other endogenous peptide antibiotics of vertebrates [J]. J Leukoc Biol, 1995; 58(2)∶128.
12.	Porter EM, Liu L, Oren A, et al. Localization of human intestinal defensin 5 in Paneth cell granules [J]. Infect Immun, 1997; 65(6)∶2389.
13.	Porter EM, van Dam E, Valore EV, et al. Broadspectrum antimicrobial activity of human intestinal defensin 5 [J]. Infect Immun, 1997; 65(6)∶2396.
14.	Lehrer RI, Barton A, Daher KA, et al. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity [J]. J Clin Invest, 1989 ; 84(2)∶553.
15.	Bevins CL, MartinPorter E, Ganz T. Defensins and innate host defence of the gastrointestinal tract [J]. Gut, 1999; 45(6)∶911.
16.	Ouellette AJ, Satchell DP, Hsieh MM, et al. Characterization of luminal paneth cell alphadefensins in mouse small intestine. Attenuated antimicrobial activities of peptides with truncated amino termini [J]. J Biol Chem, 2000; 275(43)∶33969.
17.	Ganz T. Microbiology: Gut defence [J]. Nature, 2003; 422(6931)∶478.
18.	Linzmeier R, Ho CH, Hoang BV, et al. A 450kb contig of defensin genes on human chromosome 8p23 [J]. Gene, 1999; 233(1-2)∶205.
19.	Ayabe T, Satchell DP, Wilson CL, et al. Secretion of microbicidal alphadefensins by intestinal Paneth cells in response to bacteria [J]. Nat Immunol, 2000; 1(2)∶113.
20.	Wilson CL, Ouellette AJ, Satchell DP, et al. Regulation of intestinal alphadefensin activation by the metalloproteinase matrilysin in innate host defense [J]. Science, 1999; 286(5437)∶113.
21.	Selsted ME, Miller SI, Henschen AH, et al. Enteric defensins: antibiotic peptide components of intestinal host defense [J]. J Cell Biol, 1992; 118(4)∶929.
22.	Salzman NH, Ghosh D, Huttner KM, et al. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin [J]. Nature, 2003; 422(6931)∶522.
23.	方文惠，姚永明，施国志，等. 肠源性防御素与肠道天然免疫 [J]. 解放军医学杂志， 2000； 25（6）∶463.
24.	Schonwetter BS, Stolzenberg ED, Zasloff MA. Epithelial antibiotics induced at sites of inflammation [J]. Science, 1995; 267(5204)∶1645.
25.	李全生，张肇达，陈晓理，等. 实验性胰腺炎小鼠小肠隐凹素4mRNA表达变化的研究 [J]. 四川大学学报（医学版）， 2003； 34（1）∶92.
26.	Cunliffe RN, Rose FR, Keyte J, et al. 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 [J]. Gut, 2001; 48(2)∶176.
27.	Shirafuji Y, Tanabe H, Satchell DP, et al. Structural determinants of procryptdin recognition and cleavage by matrix metalloproteinase7 [J]. J Biol Chem, 2003; 278(10)∶7910.
28.	Quayle AJ, Porter EM, Nussbaum AA, et al.. Gene expression, immunolocalization, and secretion of human defensin5 in human female reproductive tract [J]. Am J Pathol, 1998; 152(5)∶1247.
29.	Diamond G, Bevins CL. betaDefensins: endogenous antibiotics of the innate host defense response [J]. Clin Immunol Immunopathol, 1998; 88(3)∶221.
30.	Grandjean V, Vincent S, Martin L, et al.. Antimicrobial protection of the mouse testis: synthesis of defensins of the cryptdin family [J]. Biol Reprod, 1997; 57(5)∶1115.
31.	Frye M, Bargon J, Dauletbaev N, et al.. Expression of human alphadefensin 5 (HD5) mRNA in nasal and bronchial epithelial cells [J]. J Clin Pathol, 2000; 53(10)∶770.

1. Ganz T, Selsted ME, Szklarek D, et al. Defensins. Natural peptide antibiotics of human neutrophils [J]. J Clin Invest, 1985; 76(4)∶1427.
2. Rice WG, Ganz T, Kinkade JM Jr, et al. Defensinrich dense granules of human neutrophils [J]. Blood, 1987; 70(3)∶757.
3. Lehrer RI, Ganz T, Selsted ME. Defensins: endogenous antibiotic peptides of animal cells [J]. Cell, 1991; 64(2)∶229.
4. Ogata K, Linzer BA, Zuberi RI, et al. Activity of defensins from human neutrophilic granulocytes against Mycobacterium aviumMycobacterium intracellulare [J]. Infect Immun, 1992; 60(11)∶4720.
5. Gabay JE, Almeida RP. Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin [J]. Curr Opin Immunol, 1993; 5(1)∶97.
6. Jones DE, Bevins CL. Paneth cells of the human small intestine express an antimicrobial peptide gene [J]. J Biol Chem, 1992; 267(32)∶23216.
7. Bevins CL, Jones DE, Dutra A, et al. Human enteric defensin genes: chromosomal map position and a model for possible evolutionary relationships [J]. Genomics, 1996; 31(1)∶95.
8. Ghosh D, Porter E, Shen B, et al. Paneth cell trypsin is the processing enzyme for human defensin5 [J]. Nat Immunol, 2002; 3(6)∶583.
9. Com E, Bourgeon F, Evrard B, et al. Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans [J]. Biol Reprod, 2003; 68(1)∶95.
10. Porter EM, Poles MA, Lee JS, et al. Isolation of human intestinal defensins from ileal neobladder urine [J]. FEBS Lett, 1998; 434(3)∶272.
11. Martin E, Ganz T, Lehrer RI. Defensins and other endogenous peptide antibiotics of vertebrates [J]. J Leukoc Biol, 1995; 58(2)∶128.
12. Porter EM, Liu L, Oren A, et al. Localization of human intestinal defensin 5 in Paneth cell granules [J]. Infect Immun, 1997; 65(6)∶2389.
13. Porter EM, van Dam E, Valore EV, et al. Broadspectrum antimicrobial activity of human intestinal defensin 5 [J]. Infect Immun, 1997; 65(6)∶2396.
14. Lehrer RI, Barton A, Daher KA, et al. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity [J]. J Clin Invest, 1989 ; 84(2)∶553.
15. Bevins CL, MartinPorter E, Ganz T. Defensins and innate host defence of the gastrointestinal tract [J]. Gut, 1999; 45(6)∶911.
16. Ouellette AJ, Satchell DP, Hsieh MM, et al. Characterization of luminal paneth cell alphadefensins in mouse small intestine. Attenuated antimicrobial activities of peptides with truncated amino termini [J]. J Biol Chem, 2000; 275(43)∶33969.
17. Ganz T. Microbiology: Gut defence [J]. Nature, 2003; 422(6931)∶478.
18. Linzmeier R, Ho CH, Hoang BV, et al. A 450kb contig of defensin genes on human chromosome 8p23 [J]. Gene, 1999; 233(1-2)∶205.
19. Ayabe T, Satchell DP, Wilson CL, et al. Secretion of microbicidal alphadefensins by intestinal Paneth cells in response to bacteria [J]. Nat Immunol, 2000; 1(2)∶113.
20. Wilson CL, Ouellette AJ, Satchell DP, et al. Regulation of intestinal alphadefensin activation by the metalloproteinase matrilysin in innate host defense [J]. Science, 1999; 286(5437)∶113.
21. Selsted ME, Miller SI, Henschen AH, et al. Enteric defensins: antibiotic peptide components of intestinal host defense [J]. J Cell Biol, 1992; 118(4)∶929.
22. Salzman NH, Ghosh D, Huttner KM, et al. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin [J]. Nature, 2003; 422(6931)∶522.
23. 方文惠，姚永明，施国志，等. 肠源性防御素与肠道天然免疫 [J]. 解放军医学杂志， 2000； 25（6）∶463.
24. Schonwetter BS, Stolzenberg ED, Zasloff MA. Epithelial antibiotics induced at sites of inflammation [J]. Science, 1995; 267(5204)∶1645.
25. 李全生，张肇达，陈晓理，等. 实验性胰腺炎小鼠小肠隐凹素4mRNA表达变化的研究 [J]. 四川大学学报（医学版）， 2003； 34（1）∶92.
26. Cunliffe RN, Rose FR, Keyte J, et al. 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 [J]. Gut, 2001; 48(2)∶176.
27. Shirafuji Y, Tanabe H, Satchell DP, et al. Structural determinants of procryptdin recognition and cleavage by matrix metalloproteinase7 [J]. J Biol Chem, 2003; 278(10)∶7910.
28. Quayle AJ, Porter EM, Nussbaum AA, et al.. Gene expression, immunolocalization, and secretion of human defensin5 in human female reproductive tract [J]. Am J Pathol, 1998; 152(5)∶1247.
29. Diamond G, Bevins CL. betaDefensins: endogenous antibiotics of the innate host defense response [J]. Clin Immunol Immunopathol, 1998; 88(3)∶221.
30. Grandjean V, Vincent S, Martin L, et al.. Antimicrobial protection of the mouse testis: synthesis of defensins of the cryptdin family [J]. Biol Reprod, 1997; 57(5)∶1115.
31. Frye M, Bargon J, Dauletbaev N, et al.. Expression of human alphadefensin 5 (HD5) mRNA in nasal and bronchial epithelial cells [J]. J Clin Pathol, 2000; 53(10)∶770.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Progress on Human Defensin 5

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