Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense.
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.
Wilson
C L
CL
Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson_c@kids.wustl.edu
Ouellette
A J
AJ
Satchell
D P
DP
Ayabe
T
T
López-Boado
Y S
YS
Stratman
J L
JL
Hultgren
S J
SJ
Matrisian
L M
LM
Parks
W C
WC
D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D003594:Cytoplasmic Granules / Q000201:enzymology; D004926:Escherichia coli / Q000254:growth & development; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D007421:Intestine, Small / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D008297:Male; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019879:Paneth Cells / Q000201:enzymology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000254:growth & development / Q000472:pathogenicity; D014020:Tissue Extracts / Q000494:pharmacology
D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D014020:Tissue Extracts; C059569:cryptdin; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7