Paneth cell trypsin is the processing enzyme for human defensin-5

Dipankar Ghosh, Edith Porter, Bo Shen, Sarah K. Lee, Dennis Wilk, Judith Drazba, Satya P. Yadav, John W. Crabb, Tomas Ganz, Charles L Bevins

Research output: Contribution to journalArticle

333 Scopus citations

Abstract

The antimicrobial peptide human α-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 μg 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.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalNature Immunology
Volume3
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Ghosh, D., Porter, E., Shen, B., Lee, S. K., Wilk, D., Drazba, J., Yadav, S. P., Crabb, J. W., Ganz, T., & Bevins, C. L. (2002). Paneth cell trypsin is the processing enzyme for human defensin-5. Nature Immunology, 3(6), 583-590. https://doi.org/10.1038/ni797