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

Precursors of alpha-defensin peptides require activation for bactericidal a ctivity. In mouse small intestine, matrilysin colocalized with alpha-defens ins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro se gment from cryptdin precursors. Matrilysin-deficient (MAT(-/-)) mice Lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide p reparations from MAT(-/-) mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent i n MAT(-/-) mice than in MAT(+/+) mice Thus, matrilysin functions in intesti nal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.