Nature Immunology
3, 583 - 590 (2002)
Published online: 20 May 2002; | doi:10.1038/ni797
Paneth cell trypsin is the processing enzyme for human
defensin-5Dipankar Ghosh1, 2, Edith Porter3, 4, Bo Shen1, 5, Sarah K. Lee1, 2, Dennis Wilk1, 2, Judith Drazba2, Satya P. Yadav2, John W. Crabb2, 6, Tomas Ganz3
& Charles L. Bevins1, 2, 5, 71
Department of Immunology, The Cleveland Clinic
Foundation, 9500 Euclid Ave., Cleveland,
OH 44195, USA. 2
The Lerner Research Institute, The Cleveland
Clinic Foundation, 9500 Euclid Ave.,
Cleveland, OH 44195, USA. 3
Department of Medicine, UCLA School of
Medicine, 10833 Le Conte Ave., Los Angeles,
CA 90095, USA. 4
Department of Biological Sciences, California
State University, 5151 State University Dr., Los Angeles,
CA 90032, USA. 5
Department of Gastroenterology, The Cleveland
Clinic Foundation 9500 Euclid Ave.,
Cleveland, OH 44195, USA. 6
The Cole Eye Institute, The Cleveland Clinic
Foundation, 9500 Euclid Ave., Cleveland,
OH 44195, USA. 7
Department of Colorectal Surgery, The Cleveland
Clinic Foundation 9500 Euclid Ave.,
Cleveland, OH 44195, USA.
Correspondence should be addressed to Charles L. Bevins bevinsc@ccf.orgThe antimicrobial peptide human  -defensin 5 (HD5) is
expressed in Paneth cells, secretory epithelial cells in the small intestine.
Unlike other characterized defensins, HD5 is stored in secretory vesicles as a
propeptide. The storage quantities of HD5 are  90−450  g per
cm2 of mucosal surface area, which is sufficient to generate
microbicidal concentrations in the intestinal lumen. HD5 peptides isolated from
the intestinal lumen are proteolytically processed forms—HD5(56−94)
and HD5(63−94)—that are cleaved at the
Arg55-Ala56 and
Arg62-Thr63 sites, respectively. We show here
that a specific pattern of trypsin isozymes is expressed in Paneth cells, that
trypsin colocalizes with HD5 and that this protease can efficiently cleave HD5
propeptide to forms identical to those isolated in vivo. By acting as a
prodefensin convertase in human Paneth cells, trypsin is involved in the
regulation of innate immunity in the small intestine.
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