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Regulation of Intestinal α-Defensin Activation by the Metalloproteinase Matrilysin in Innate Host Defense

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Science  01 Oct 1999:
Vol. 286, Issue 5437, pp. 113-117
DOI: 10.1126/science.286.5437.113

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Abstract

Precursors of α-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with α-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.

  • * To whom correspondence should be addressed. E-mail: wilson_c{at}kids.wustl.edu

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