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Infect Immun, July 1998, p. 3255-3263, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Potential Role of Epithelial Cell-Derived Histone H1 Proteins in Innate Antimicrobial Defense in the Human Gastrointestinal Tract

F. R. A. J. Rose,1,2 K. Bailey,3 J. W. Keyte,3 W. C. Chan,4 D. Greenwood,5 and Y. R. Mahida1,2,*

Divisions of Gastroenterology1 and Microbiology,5 Departments of Biochemistry3 and Pharmaceutical Sciences,4 and Institute of Infections and Immunity,2 University of Nottingham, Nottingham, United Kingdom

Received 30 January 1998/Returned for modification 26 March 1998/Accepted 15 April 1998

In the human gastrointestinal tract, microorganisms are present in large numbers in the colon but are sparse in the proximal small intestine. In this study, we have shown that acid extracts of fresh human terminal ileal mucosal samples mediate antimicrobial activity. Following cation-exchange chromatography, one of the eluted fractions demonstrated antibacterial activity against bacteria normally resident in the human colonic lumen. This activity was further fractionated by reverse-phase high-performance liquid chromatography and identified as histone H1 and its fragments. We have also shown that in tissue sections, immunoreactive histone H1 is present in the cytoplasm of villus epithelial cells. In vitro culturing of detached (from the basement membrane) villus epithelial cells led to the release of antimicrobial histone H1 proteins, while the cells demonstrated ultrastructural features of programmed cell death. Our studies suggest that cytoplasmic histone H1 may provide protection against penetration by microorganisms into villus epithelial cells. Moreover, intestinal epithelial cells released into the lumen may mediate antimicrobial activity by releasing histone H1 proteins and their fragments.

* Corresponding author. Mailing address: Division of Gastroenterology, University Hospital, Queens Medical Centre, Nottingham NG7 2UH, United Kingdom. Phone: 115 970 9973. Fax: 115 942 2232. E-mail: muzyrm{at}mmn1.medical.nottingham.ac.uk.

Infect Immun, July 1998, p. 3255-3263, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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