• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. Aug 2, 1992; 118(4): 929–936.
PMCID: PMC2289569

Enteric defensins: antibiotic peptide components of intestinal host defense

Abstract

Five intestinal defensins, termed cryptdins 1-5, have been purified from mouse small bowel, sequenced, and localized to the epithelium by immunohistochemistry. Although identified as members of the defensin peptide family by peptide sequencing, enteric defensins are novel in that four cryptdins have amino termini which are three to six residues longer than those of leukocyte-derived defensins. A fifth cryptdin is the first defensin to diverge from the previously invariant spacing of cysteines in the peptide structure. The most abundant enteric defensin, cryptdin-1, had antimicrobial activity against an attenuated phoP mutant of Salmonella typhimurium but was not active against the virulent wild-type parent. Immunohistochemical localization demonstrated that cryptdin-1, and probably cryptdins 2 and 3, occur exclusively in Paneth cells, where the peptides appear to be associated with cytoplasmic granules. Biochemical and immunologic analysis of the luminal contents of the small intestine suggest that cryptdin peptides are secreted into the lumen, similar to Paneth cell secretion of lysozyme. The presence of several enteric defensins in the intestinal epithelium, evidence of their presence in the lumen, and the antibacterial activity of cryptdin-1 suggest that these peptides contribute to the antimicrobial barrier function of the small bowel mucosa.

Full Text

The Full Text of this article is available as a PDF (4.0M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ouellette AJ, Miller SI, Henschen AH, Selsted ME. Purification and primary structure of murine cryptdin-1, a Paneth cell defensin. FEBS Lett. 1992 Jun 15;304(2-3):146–148. [PubMed]
  • Bjerknes M, Cheng H. The stem-cell zone of the small intestinal epithelium. I. Evidence from Paneth cells in the adult mouse. Am J Anat. 1981 Jan;160(1):51–63. [PubMed]
  • Cheng H, Merzel J, Leblond CP. Renewal of Paneth cells in the small intestine of the mouse. Am J Anat. 1969 Dec;126(4):507–525. [PubMed]
  • Daher KA, Lehrer RI, Ganz T, Kronenberg M. Isolation and characterization of human defensin cDNA clones. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7327–7331. [PMC free article] [PubMed]
  • Fields PI, Groisman EA, Heffron F. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science. 1989 Feb 24;243(4894 Pt 1):1059–1062. [PubMed]
  • Ganz T. Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytes. Infect Immun. 1987 Mar;55(3):568–571. [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]
  • Ganz T, Rayner JR, Valore EV, Tumolo A, Talmadge K, Fuller F. The structure of the rabbit macrophage defensin genes and their organ-specific expression. J Immunol. 1989 Aug 15;143(4):1358–1365. [PubMed]
  • Ganz T, Selsted ME, Lehrer RI. Defensins. Eur J Haematol. 1990 Jan;44(1):1–8. [PubMed]
  • Hammer MF, Schilling JW, Prager EM, Wilson AC. Recruitment of lysozyme as a major enzyme in the mouse gut: duplication, divergence, and regulatory evolution. J Mol Evol. 1987;24(3):272–279. [PubMed]
  • Hill CP, Yee J, Selsted ME, Eisenberg D. Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991 Mar 22;251(5000):1481–1485. [PubMed]
  • Kagan BL, Selsted ME, Ganz T, Lehrer RI. Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc Natl Acad Sci U S A. 1990 Jan;87(1):210–214. [PMC free article] [PubMed]
  • Kent SB. Chemical synthesis of peptides and proteins. Annu Rev Biochem. 1988;57:957–989. [PubMed]
  • Keshav S, Lawson L, Chung LP, Stein M, Perry VH, Gordon S. Tumor necrosis factor mRNA localized to Paneth cells of normal murine intestinal epithelium by in situ hybridization. J Exp Med. 1990 Jan 1;171(1):327–332. [PMC free article] [PubMed]
  • Lehrer RI, Barton A, Daher KA, Harwig SS, Ganz T, Selsted ME. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest. 1989 Aug;84(2):553–561. [PMC free article] [PubMed]
  • Lehrer RI, Ganz T, Selsted ME. Defensins: endogenous antibiotic peptides of animal cells. Cell. 1991 Jan 25;64(2):229–230. [PubMed]
  • Lehrer RI, Rosenman M, Harwig SS, Jackson R, Eisenhauer P. Ultrasensitive assays for endogenous antimicrobial polypeptides. J Immunol Methods. 1991 Mar 21;137(2):167–173. [PubMed]
  • Miller SI. PhoP/PhoQ: macrophage-specific modulators of Salmonella virulence? Mol Microbiol. 1991 Sep;5(9):2073–2078. [PubMed]
  • Miller SI, Kukral AM, Mekalanos JJ. A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5054–5058. [PMC free article] [PubMed]
  • Miller SI, Pulkkinen WS, Selsted ME, Mekalanos JJ. Characterization of defensin resistance phenotypes associated with mutations in the phoP virulence regulon of Salmonella typhimurium. Infect Immun. 1990 Nov;58(11):3706–3710. [PMC free article] [PubMed]
  • Ouellette AJ, Cordell B. Accumulation of abundant messenger ribonucleic acids during postnatal development of mouse small intestine. Gastroenterology. 1988 Jan;94(1):114–121. [PubMed]
  • Ouellette AJ, Lualdi JC. A novel mouse gene family coding for cationic, cysteine-rich peptides. Regulation in small intestine and cells of myeloid origin. J Biol Chem. 1990 Jun 15;265(17):9831–9837. [PubMed]
  • Ouellette AJ, Pravtcheva D, Ruddle FH, James M. Localization of the cryptdin locus on mouse chromosome 8. Genomics. 1989 Aug;5(2):233–239. [PubMed]
  • Pardi A, Hare DR, Selsted ME, Morrison RD, Bassolino DA, Bach AC., 2nd Solution structures of the rabbit neutrophil defensin NP-5. J Mol Biol. 1988 Jun 5;201(3):625–636. [PubMed]
  • Peeters T, Vantrappen G. The Paneth cell: a source of intestinal lysozyme. Gut. 1975 Jul;16(7):553–558. [PMC free article] [PubMed]
  • Pulkkinen WS, Miller SI. A Salmonella typhimurium virulence protein is similar to a Yersinia enterocolitica invasion protein and a bacteriophage lambda outer membrane protein. J Bacteriol. 1991 Jan;173(1):86–93. [PMC free article] [PubMed]
  • Satoh Y, Ishikawa K, Oomori Y, Yamano M, Ono K. Effects of cholecystokinin and carbamylcholine on Paneth cell secretion in mice: a comparison with pancreatic acinar cells. Anat Rec. 1989 Oct;225(2):124–132. [PubMed]
  • Selsted ME, Harwig SS. Purification, primary structure, and antimicrobial activities of a guinea pig neutrophil defensin. Infect Immun. 1987 Sep;55(9):2281–2286. [PMC free article] [PubMed]
  • Selsted ME, Harwig SS. Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide. J Biol Chem. 1989 Mar 5;264(7):4003–4007. [PubMed]
  • Sparkes RS, Kronenberg M, Heinzmann C, Daher KA, Klisak I, Ganz T, Mohandas T. Assignment of defensin gene(s) to human chromosome 8p23. Genomics. 1989 Aug;5(2):240–244. [PubMed]
  • SPEECE AJ. HISTOCHEMICAL DISTRIBUTION OF LYSOZYME ACTIVITY IN ORGANS OF NORMAL MICE AND RADIATION CHIMERAS. J Histochem Cytochem. 1964 May;12:384–391. [PubMed]
  • Staley MW, Trier JS. Morphologic heterogeneity of mouse Paneth cell granules before and after secretory stimulation. Am J Anat. 1965 Nov;117(3):365–383. [PubMed]
  • Troughton WD, Trier JS. Paneth and goblet cell renewal in mouse duodenal crypts. J Cell Biol. 1969 Apr;41(1):251–268. [PMC free article] [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...