title: 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.
abstract: OBJECTIVE
  Intestinal epithelial cell derived antimicrobial peptides of the defensin family may play a major role in host defence against microorganisms. Our aims were to (i) isolate, characterise, and investigate the processing of human defensin 5 (HD-5) in normal Paneth cells and (ii) investigate expression of HD-5 in active inflammatory bowel disease (IBD).
  
  
  METHODS
  Antiserum raised against chemically synthesised putative mature HD-5 was used for immunohistochemistry and purification of HD-5 from extracts of normal terminal ileal crypts.
  
  
  RESULTS
  In normal and Crohn's disease terminal ileum, HD-5 immunoreactivity was seen in Paneth cells and in some villous epithelial cells. Normal colonic mucosa did not express HD-5 but HD-5 immunoreactivity was seen in cells in the colonic crypt region of many IBD samples. N-terminal amino acid sequence analysis of HD-5 purified from normal terminal ileal Paneth cells consistently showed the predicted sequence of the precursor form of the peptide. Following stimulation of isolated intact normal terminal ileal crypts, a truncated form of HD-5, with the N-terminal sequence GEDNQLAIS, was detected in the supernatant.
  
  
  CONCLUSIONS
  (i) HD-5 is present only in the precursor form in normal terminal ileal Paneth cells and is processed to the mature form during and/or after secretion, (ii) some villous epithelial cells express HD-5, and (iii) HD-5 is expressed by metaplastic Paneth cells in the colon in IBD.
authors.affiliation: Division of Gastroenterology, University of Nottingham, UK.
authors.forename: R N
authors.initials: RN
authors.lastname: Cunliffe
authors.forename: F R
authors.initials: FR
authors.lastname: Rose
authors.forename: J
authors.initials: J
authors.lastname: Keyte
authors.forename: L
authors.initials: L
authors.lastname: Abberley
authors.forename: W C
authors.initials: WC
authors.lastname: Chan
authors.forename: Y R
authors.initials: YR
authors.lastname: Mahida
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015169:Colony Count, Microbial; D023082:Defensins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D004586:Electrophoresis; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000096:biosynthesis; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D019879:Paneth Cells / Q000378:metabolism*; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D020539:Sequence Analysis, Protein
chemical_list: D023082:Defensins; D007106:Immune Sera; D011498:Protein Precursors