Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense.

Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, López-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC
Science. 1999 286 (5437): 113-7

PMID: 10506557 · DOI:10.1126/science.286.5437.113

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.

MeSH Terms (22)

Amino Acid Sequence Animals Catalysis Cytoplasmic Granules Escherichia coli Escherichia coli Infections Female Humans Immunity, Innate Immunity, Mucosal Intestinal Mucosa Intestine, Small Male Matrix Metalloproteinase 7 Metalloendopeptidases Mice Molecular Sequence Data Paneth Cells Protein Precursors Recombinant Fusion Proteins Salmonella typhimurium Tissue Extracts

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