title: Paneth cell trypsin is the processing enzyme for human defensin-5.
abstract: The antimicrobial peptide human alpha-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 approximately 90 450 microg 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.
authors.affiliation: Department of Immunology, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Ghosh
authors.forename: Edith
authors.initials: E
authors.lastname: Porter
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Lee
authors.forename: Dennis
authors.initials: D
authors.lastname: Wilk
authors.forename: Judith
authors.initials: J
authors.lastname: Drazba
authors.forename: Satya P
authors.initials: SP
authors.lastname: Yadav
authors.forename: John W
authors.initials: JW
authors.lastname: Crabb
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D018928:Immunity, Mucosal; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D019879:Paneth Cells / Q000201:enzymology* / Q000276:immunology*; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014357:Trypsin / Q000378:metabolism*; D023084:alpha-Defensins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D020033:Protein Isoforms; D011498:Protein Precursors; D012333:RNA, Messenger; D023084:alpha-Defensins; D014357:Trypsin