• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. May 1998; 152(5): 1247–1258.
PMCID: PMC1858596

Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract.

Abstract

This study describes the novel localization of the antimicrobial peptide human intestinal defensin-5 (HD-5) in female genital tract epithelia. Using a 3' rapid amplification of cDNA ends (RACE) protocol, HD-5 was cloned from a vaginal epithelial cell RNA preparation, and its identity was confirmed by sequencing. Tissue samples from multiple donors were subsequently screened for HD-5 expression by reverse transcription polymerase chain reaction. HD-5 message was invariantly expressed by normal vagina and ectocervix and inflamed fallopian tube, but variably expressed by normal endocervix, endometrium, and fallopian tube (60, 64, and 29% of specimens, respectively). Expression in endometrium was the highest during the early secretory phase of the menstrual cycle. Using immunohistochemistry and confocal microscopy, HD-5 peptide was localized in the upper half of the stratified squamous epithelium of the vagina and ectocervix, with the intensity of cellular staining increasing toward the lumen. In positive endocervix, endometrium, and fallopian tube specimens, HD-5 was located in apically oriented granules and on the apical surface of a proportion of columnar epithelial cells. Using Western blot analysis, secreted HD-5 was detected in cervicovaginal lavages, with the highest concentrations found during the secretory phase of the menstrual cycle. We hypothesize that HD-5 is an intrinsic component of the female urogenital innate immune defense system and that its expression may be modulated by hormonal and proinflammatory factors.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Paganini-Hill Annlia, Ross Ronald K, Henderson Brian E. Aspirin use and chronic diseases: Authors' reply. BMJ. 1990 Jan 13;300(6717):a117–117. [PMC free article]
  • Schumacher GF. Biochemistry of cervical mucus. Fertil Steril. 1970 Oct;21(10):697–705. [PubMed]
  • Schumacher GF, Kim MH, Hosseinian AH, Dupon C. Immunoglobulins, proteinase inhibitors, albumin, and lysozyme in human cervical mucus. I. Communication: hormonal profiles and cervical mucus changes--methods and results. Am J Obstet Gynecol. 1977 Nov 15;129(6):629–636. [PubMed]
  • Cohen MS, Britigan BE, French M, Bean K. Preliminary observations on lactoferrin secretion in human vaginal mucus: variation during the menstrual cycle, evidence of hormonal regulation, and implications for infection with Neisseria gonorrhoeae. Am J Obstet Gynecol. 1987 Nov;157(5):1122–1125. [PubMed]
  • Heinonen PK, Teisala K, Punnonen R, Miettinen A, Lehtinen M, Paavonen J. Anatomic sites of upper genital tract infection. Obstet Gynecol. 1985 Sep;66(3):384–390. [PubMed]
  • Cleary RE, Jones RB. Recovery of Chlamydia trachomatis from the endometrium in infertile women with serum antichlamydial antibodies. Fertil Steril. 1985 Aug;44(2):233–235. [PubMed]
  • Spence MR, Blanco LJ, Patel J, Brockman MT. A comparative evaluation of vaginal, cervical and peritoneal flora in normal, healthy women: a preliminary report. Sex Transm Dis. 1982 Jan-Mar;9(1):37–40. [PubMed]
  • Lehrer RI, Lichtenstein AK, Ganz T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol. 1993;11:105–128. [PubMed]
  • Yasin B, Harwig SS, Lehrer RI, Wagar EA. Susceptibility of Chlamydia trachomatis to protegrins and defensins. Infect Immun. 1996 Mar;64(3):709–713. [PMC free article] [PubMed]
  • Greenwald GI, Ganz T. Defensins mediate the microbicidal activity of human neutrophil granule extract against Acinetobacter calcoaceticus. Infect Immun. 1987 Jun;55(6):1365–1368. [PMC free article] [PubMed]
  • Aley SB, Zimmerman M, Hetsko M, Selsted ME, Gillin FD. Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides. Infect Immun. 1994 Dec;62(12):5397–5403. [PMC free article] [PubMed]
  • Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986 Dec;60(3):1068–1074. [PMC free article] [PubMed]
  • Valore EV, Ganz T. Posttranslational processing of defensins in immature human myeloid cells. Blood. 1992 Mar 15;79(6):1538–1544. [PubMed]
  • Liu L, Zhao C, Heng HH, Ganz T. The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry. Genomics. 1997 Aug 1;43(3):316–320. [PubMed]
  • Selsted ME, Szklarek D, Lehrer RI. Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect Immun. 1984 Jul;45(1):150–154. [PMC free article] [PubMed]
  • Patterson-Delafield J, Martinez RJ, Lehrer RI. Microbicidal cationic proteins in rabbit alveolar macrophages: a potential host defense mechanism. Infect Immun. 1980 Oct;30(1):180–192. [PMC free article] [PubMed]
  • Ouellette AJ, Greco RM, James M, Frederick D, Naftilan J, Fallon JT. Developmental regulation of cryptdin, a corticostatin/defensin precursor mRNA in mouse small intestinal crypt epithelium. J Cell Biol. 1989 May;108(5):1687–1695. [PMC free article] [PubMed]
  • Jones DE, Bevins CL. Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem. 1992 Nov 15;267(32):23216–23225. [PubMed]
  • Jones DE, Bevins CL. Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett. 1993 Jan 4;315(2):187–192. [PubMed]
  • Svinarich DM, Wolf NA, Gomez R, Gonik B, Romero R. Detection of human defensin 5 in reproductive tissues. Am J Obstet Gynecol. 1997 Feb;176(2):470–475. [PubMed]
  • Selsted ME, Miller SI, Henschen AH, Ouellette AJ. Enteric defensins: antibiotic peptide components of intestinal host defense. J Cell Biol. 1992 Aug;118(4):929–936. [PMC free article] [PubMed]
  • Porter EM, van Dam E, Valore EV, Ganz T. Broad-spectrum antimicrobial activity of human intestinal defensin 5. Infect Immun. 1997 Jun;65(6):2396–2401. [PMC free article] [PubMed]
  • Schonwetter BS, Stolzenberg ED, Zasloff MA. Epithelial antibiotics induced at sites of inflammation. Science. 1995 Mar 17;267(5204):1645–1648. [PubMed]
  • Diamond G, Jones DE, Bevins CL. Airway epithelial cells are the site of expression of a mammalian antimicrobial peptide gene. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4596–4600. [PMC free article] [PubMed]
  • Diamond G, Zasloff M, Eck H, Brasseur M, Maloy WL, Bevins CL. Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3952–3956. [PMC free article] [PubMed]
  • Selsted ME, Tang YQ, Morris WL, McGuire PA, Novotny MJ, Smith W, Henschen AH, Cullor JS. Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. J Biol Chem. 1993 Mar 25;268(9):6641–6648. [PubMed]
  • Harder J, Bartels J, Christophers E, Schröder JM. A peptide antibiotic from human skin. Nature. 1997 Jun 26;387(6636):861–861. [PubMed]
  • Bensch KW, Raida M, Mägert HJ, Schulz-Knappe P, Forssmann WG. hBD-1: a novel beta-defensin from human plasma. FEBS Lett. 1995 Jul 17;368(2):331–335. [PubMed]
  • Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell. 1997 Feb 21;88(4):553–560. [PubMed]
  • Zhao C, Wang I, Lehrer RI. Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett. 1996 Nov 4;396(2-3):319–322. [PubMed]
  • Pudney J, Anderson DJ. Immunobiology of the human penile urethra. Am J Pathol. 1995 Jul;147(1):155–165. [PMC free article] [PubMed]
  • Mok SC, Lo KW, Tsao SW. Direct cycle sequencing of mutated alleles detected by PCR single-strand conformation polymorphism analysis. Biotechniques. 1993 May;14(5):790–794. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Moll R, Levy R, Czernobilsky B, Hohlweg-Majert P, Dallenbach-Hellweg G, Franke WW. Cytokeratins of normal epithelia and some neoplasms of the female genital tract. Lab Invest. 1983 Nov;49(5):599–610. [PubMed]
  • Porter EM, Liu L, Oren A, Anton PA, Ganz T. Localization of human intestinal defensin 5 in Paneth cell granules. Infect Immun. 1997 Jun;65(6):2389–2395. [PMC free article] [PubMed]
  • Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. [PMC free article] [PubMed]
  • Barnathan ES, Raghunath PN, Tomaszewski JE, Ganz T, Cines DB, Higazi A al-R Immunohistochemical localization of defensin in human coronary vessels. Am J Pathol. 1997 Mar;150(3):1009–1020. [PMC free article] [PubMed]
  • Ouellette AJ, Selsted ME. Paneth cell defensins: endogenous peptide components of intestinal host defense. FASEB J. 1996 Sep;10(11):1280–1289. [PubMed]
  • Peeters T, Vantrappen G. The Paneth cell: a source of intestinal lysozyme. Gut. 1975 Jul;16(7):553–558. [PMC free article] [PubMed]
  • Mulherkar R, Rao RS, Wagle AS, Patki V, Deo MG. Enhancing factor, a Paneth cell specific protein from mouse small intestines: predicted amino acid sequence from RT-PCR amplified cDNA and its expression. Biochem Biophys Res Commun. 1993 Sep 30;195(3):1254–1263. [PubMed]
  • Zanetti M, Litteri L, Griffiths G, Gennaro R, Romeo D. Stimulus-induced maturation of probactenecins, precursors of neutrophil antimicrobial polypeptides. J Immunol. 1991 Jun 15;146(12):4295–4300. [PubMed]
  • Panyutich A, Shi J, Boutz PL, Zhao C, Ganz T. Porcine polymorphonuclear leukocytes generate extracellular microbicidal activity by elastase-mediated activation of secreted proprotegrins. Infect Immun. 1997 Mar;65(3):978–985. [PMC free article] [PubMed]
  • Russell JP, Diamond G, Tarver AP, Scanlin TF, Bevins CL. Coordinate induction of two antibiotic genes in tracheal epithelial cells exposed to the inflammatory mediators lipopolysaccharide and tumor necrosis factor alpha. Infect Immun. 1996 May;64(5):1565–1568. [PMC free article] [PubMed]
  • Stolzenberg ED, Anderson GM, Ackermann MR, Whitlock RH, Zasloff M. Epithelial antibiotic induced in states of disease. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8686–8690. [PMC free article] [PubMed]
  • Sánchez R, Villagrán E, Concha M, Cornejo R. Ultrastructural analysis of the attachment sites of Escherichia coli to the human spermatozoon after in vitro migration through estrogenic cervical mucus. Int J Fertil. 1989 Sep-Oct;34(5):363–367. [PubMed]
  • Friberg J, Fullan N. Attachment of Escherichia coli to human spermatozoa. Am J Obstet Gynecol. 1983 Jun 15;146(4):465–467. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Gene
    Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM
    OMIM record citing PubMed
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...