title: Matrix metalloproteinase-9 deficiency impairs host defense against abdominal sepsis.
abstract: Matrix metalloproteinase (MMP)-9 is involved in extracellular matrix degradation and leukocyte migration. To determine the role of MMP-9 in the innate immune response to peritonitis, MMP-9 gene-deficient (MMP-9(-/-)) and normal wild-type mice were i.p. infected with Escherichia coli. MMP-9 mRNA and pro-MMP-9 protein levels increased rapidly upon induction of peritonitis. Although MMP-9(-/-) neutrophils showed a normal phagocytosis of E. coli in vitro, MMP-9(-/-) mice displayed a reduced resistance against E. coli peritonitis, as indicated by an enhanced bacterial outgrowth in the peritoneal cavity and increased dissemination of the infection. Furthermore, the cytokine response to LPS was not influenced by MMP-9 deficiency. However, during E. coli peritonitis, MMP-9(-/-) mice showed much higher peritoneal chemokine and cytokine levels compared with wild-type mice. Despite the increased local chemokine concentrations, MMP-9(-/-) mice displayed a diminished recruitment of leukocytes to the site of infection, indicating that cellular migration was impaired. Moreover, MMP-9(-/-) mice developed more severe distant organ damage during infection. These data suggest that MMP-9 is an essential component of an effective host response to E. coli peritonitis.
authors.affiliation: Laboratory of Experimental Internal Medicine, Academic Medical Center Rm. G2-132, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. r.renckens@amc.uva.nl
authors.forename: Rosemarijn
authors.initials: R
authors.lastname: Renckens
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: H Roger
authors.initials: HR
authors.lastname: Lijnen
authors.forename: Cornelis
authors.initials: C
authors.lastname: van't Veer
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000005:Abdomen / Q000473:pathology*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011014:Pneumonia / Q000201:enzymology / Q000473:pathology; D018805:Sepsis / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D020780:Matrix Metalloproteinase 9