ORIGINAL ARTICLE

Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa

R N Cunliffe¹, M Kamal¹, F R A J Rose¹, P D James², Y R Mahida¹

¹ Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK
² Department of Pathology, University Hospital

Correspondence to:
Correspondence to:
Professor Y R Mahida, Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK;
Yash.Mahida{at} nottingham.ac.uk

Background/Aims: The normal intestinal epithelium is increasingly being recognised as an important component of the mucosal innate protection against microorganisms. Human neutrophil defensins 1–3 (HNP 1–3) and lysozyme are components of the systemic innate immunity. The aim of this study was to investigate the expression of HNP 1–3 and lysozyme in normal and active inflammatory bowel disease (IBD) mucosa.

Methods: Mucosal tissue sections were studied by immunohistochemistry using antibodies to neutrophil defensins 1–3 and lysozyme. Extracts of purified intestinal epithelial cells were used for immunoblotting studies and antimicrobial activity against the phoP negative strain of Salmonella typhimurium.

Results: Surface epithelial cells strongly immunoreactive for neutrophil defensins and lysozyme were seen in active ulcerative colitis and Crohn's disease (but not normal or inactive IBD) mucosal samples. Many of these cells coexpressed both of the antimicrobial proteins. Immunoblotting studies confirmed the expression of neutrophil defensins in extracts of purified ulcerative colitis epithelial cells, which also demonstrated antimicrobial activity.

Conclusion: HNP 1–3 and lysozyme are expressed in surface enterocytes of mucosa with active IBD and they may play an important role in intestinal host defence against luminal microorganisms.

Keywords: innate immunity; antimicrobial peptides; defensins; lysozyme

Abbreviations: AU; PAGE, acid urea; polyacrylamide gel electrophoresis; CFU, colony forming units; HNP, human neutrophil defensin polypeptide; IBD, inflammatory bowel disease; IFT, intestinal trefoil factor; PBS, phosphate buffered saline; TSB, trypticase soy broth

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Wilson, C. L., Schmidt, A. P., Pirila, E., Valore, E. V., Ferri, N., Sorsa, T., Ganz, T., Parks, W. C. (2009). Differential Processing of {alpha}- and {beta}-Defensin Precursors by Matrix Metalloproteinase-7 (MMP-7). J. Biol. Chem. 284: 8301-8311 [Abstract] [Full Text]  
• Niklaus, A. L., Pollard, J. W. (2006). Mining the Mouse Transcriptome of Receptive Endometrium Reveals Distinct Molecular Signatures for the Luminal and Glandular Epithelium. Endocrinology 147: 3375-3390 [Abstract] [Full Text]  
• Wehkamp, J., Schmid, M., Fellermann, K., Stange, E. F. (2005). Defensin deficiency, intestinal microbes, and the clinical phenotypes of Crohn's disease. J. Leukoc. Biol. 77: 460-465 [Abstract] [Full Text]  
• Cunliffe, R. N., Mahida, Y. R. (2004). Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J. Leukoc. Biol. 75: 49-58 [Abstract] [Full Text]