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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Catalysis
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Cytoplasmic Granules / enzymology
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Escherichia coli / growth & development
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Escherichia coli Infections / immunology
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Escherichia coli Infections / microbiology
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Female
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Humans
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Immunity, Innate*
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Immunity, Mucosal*
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Intestinal Mucosa / enzymology
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Intestinal Mucosa / immunology
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Intestinal Mucosa / microbiology
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Intestine, Small / enzymology
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Intestine, Small / immunology*
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Intestine, Small / microbiology
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Male
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Matrix Metalloproteinase 7
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Metalloendopeptidases / genetics
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Metalloendopeptidases / metabolism*
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Mice
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Molecular Sequence Data
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Paneth Cells / enzymology
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Recombinant Fusion Proteins / metabolism
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Salmonella typhimurium / growth & development
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Salmonella typhimurium / pathogenicity
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Tissue Extracts / pharmacology
Substances
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Protein Precursors
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Recombinant Fusion Proteins
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Tissue Extracts
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cryptdin
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Metalloendopeptidases
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Matrix Metalloproteinase 7