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

被引:173
作者
Cunliffe, RN
Rose, FRAJ
Keyte, J
Abberley, L
Chan, WC
Mahida, YR
机构
[1] Univ Nottingham, Div Gastroenterol, Nottingham NG7 2RD, England
[2] Univ Nottingham, Dept Biochem, Nottingham NG7 2RD, England
[3] Univ Nottingham, Dept Pharmaceut Sci, Nottingham NG7 2RD, England
关键词
inflammatory bowel disease; human defensin 5; Paneth cells;
D O I
10.1136/gut.48.2.176
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and aims-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.
引用
收藏
页码:176 / 185
页数:10
相关论文
共 32 条
  • [21] PODOLSKY DK, 1993, J BIOL CHEM, V268, P6694
  • [22] Localization of human intestinal defensin 5 in Paneth cell granules
    Porter, EM
    Liu, L
    Oren, A
    Anton, PA
    Ganz, T
    [J]. INFECTION AND IMMUNITY, 1997, 65 (06) : 2389 - 2395
  • [23] Broad-spectrum antimicrobial activity of human intestinal defensin 5
    Porter, EM
    vanDam, E
    Valore, EV
    Ganz, T
    [J]. INFECTION AND IMMUNITY, 1997, 65 (06) : 2396 - 2401
  • [24] Isolation of human intestinal defensins from ileal neobladder urine
    Porter, EM
    Poles, MA
    Lee, JS
    Naitoh, J
    Bevins, CL
    Ganz, T
    [J]. FEBS LETTERS, 1998, 434 (03): : 272 - 276
  • [25] Quayle AJ, 1998, AM J PATHOL, V152, P1247
  • [26] ROSE FRA, 1999, GASTROENTEROLOGY, V116, pC3935
  • [27] Potential role of epithelial cell-derived histone H1 proteins in innate antimicrobial defense in the human gastrointestinal tract
    Rose, FRAJ
    Bailey, K
    Keyte, JW
    Chan, WC
    Greenwood, D
    Mahida, YR
    [J]. INFECTION AND IMMUNITY, 1998, 66 (07) : 3255 - 3263
  • [28] ENTERIC DEFENSINS - ANTIBIOTIC PEPTIDE COMPONENTS OF INTESTINAL HOST DEFENSE
    SELSTED, ME
    MILLER, SI
    HENSCHEN, AH
    OUELLETTE, AJ
    [J]. JOURNAL OF CELL BIOLOGY, 1992, 118 (04) : 929 - 936
  • [29] Simon Gary L., 1995, P53
  • [30] PANETH AND GOBLET CELL RENEWAL IN MOUSE DUODENAL CRYPTS
    TROUGHTON, WD
    TRIER, JS
    [J]. JOURNAL OF CELL BIOLOGY, 1969, 41 (01) : 251 - +