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Alpha-defensins in the gastrointestinal tract
1Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, UK. rnc@nildram.co.uk
Molecular Immunology
|October 22, 2003
Summary
Human Defensin 5 (HD-5) is expressed in Paneth cells and villous epithelial cells, with processing occurring after secretion. In inflammatory bowel disease, HD-5 and Human Neutrophil Peptides (HNP) show altered expression, suggesting a role in host defense.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- The human intestinal tract harbors a vast bacterial flora, necessitating robust defense mechanisms.
- Antimicrobial peptides, particularly defensins, are crucial for innate immunity at mucosal surfaces.
- Human alpha-defensins (HD-5, HD-6) are expressed in intestinal Paneth cells, contributing to gut mucosal defense.
Purpose of the Study:
- To investigate the expression and localization of Human Defensin 5 (HD-5) in the human intestinal tract.
- To characterize the processing and antimicrobial activity of HD-5.
- To examine the expression of HD-5 and Human Neutrophil Peptides (HNP) in inflammatory bowel disease (IBD).
Main Methods:
- Chemical synthesis of mature HD-5 and generation of polyclonal antiserum.
- Immunohistochemistry to detect HD-5 expression in normal and inflamed intestinal tissues.
- Purification and characterization of native HD-5 using chromatography, N-terminal sequencing, and mass spectrometry.
- Antimicrobial assays to assess HD-5 activity.
- Stimulation of Paneth cell granule secretion to study HD-5 processing.
- Analysis of HNP expression in normal and IBD intestinal mucosa.
Main Results:
- HD-5 is expressed in Paneth cells and villous epithelial cells of the normal duodenum, jejunum, and ileum, but not the stomach or colon.
- In gastritis, Crohn's disease, and ulcerative colitis, HD-5 is found in metaplastic Paneth cells.
- HD-5 is stored as an inactive precursor in Paneth cells; partial processing to an active form occurs post-secretion.
- HNP are expressed by neutrophils in normal mucosa but by epithelial cells and neutrophils in active IBD.
- Antimicrobial assays showed the precursor form of HD-5 lacks activity against Salmonella.
Conclusions:
- HD-5 plays a role in intestinal innate immunity, with its expression and processing altered in inflammatory conditions.
- Partial processing of HD-5 occurs during or after secretion, potentially generating an active antimicrobial peptide.
- Altered expression of HD-5 and HNP in IBD suggests their involvement in host defense against microbial invasion during inflammation.