title: Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense.
abstract: Precursors of alpha-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT-/-) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT-/- mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT-/- mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.
authors.affiliation: Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson_c@kids.wustl.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Wilson
authors.forename: A J
authors.initials: AJ
authors.lastname: Ouellette
authors.forename: D P
authors.initials: DP
authors.lastname: Satchell
authors.forename: T
authors.initials: T
authors.lastname: Ayabe
authors.forename: Y S
authors.initials: YS
authors.lastname: López-Boado
authors.forename: J L
authors.initials: JL
authors.lastname: Stratman
authors.forename: S J
authors.initials: SJ
authors.lastname: Hultgren
authors.forename: L M
authors.initials: LM
authors.lastname: Matrisian
authors.forename: W C
authors.initials: WC
authors.lastname: Parks
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D003594:Cytoplasmic Granules / Q000201:enzymology; D004926:Escherichia coli / Q000254:growth & development; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D007421:Intestine, Small / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D008297:Male; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019879:Paneth Cells / Q000201:enzymology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000254:growth & development / Q000472:pathogenicity; D014020:Tissue Extracts / Q000494:pharmacology
chemical_list: D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D014020:Tissue Extracts; C059569:cryptdin; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7