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

Carole L. Wilson, Andre J. Ouellette, Donald P. Satchell, Tokiyoshi Ayabe, Yolanda S. López-Boado, Jennifer L. Stratman, Scott J. Hultgren, Lynn M. Matrisian, William C. Parks

Research output: Contribution to journalArticlepeer-review

862 Scopus citations

Abstract

Precursors of α-defensin peptides require activation for bactericidal activity. In mouse smart 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 maybe a common rote for this metalloproteinase in its numerous epithelial sites of expression.

Original languageEnglish
Pages (from-to)113-117
Number of pages5
JournalScience
Volume286
Issue number5437
DOIs
StatePublished - Oct 1 1999
Externally publishedYes

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