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Updated: Aug 11, 2026
Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 18, 2010
Matrix metalloproteinase-9 deficiency impairs host defense against abdominal sepsis
Rosemarijn Renckens1, Joris J T H Roelofs, Sandrine Florquin
1Laboratory 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
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.
Insights
Matrix metalloproteinase-9 (MMP-9) is crucial for controlling Escherichia coli peritonitis. MMP-9 deficiency impairs leukocyte migration, leading to increased bacterial load and organ damage, highlighting MMP-9
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Matrix metalloproteinase-9 (MMP-9) plays a role in extracellular matrix degradation and leukocyte migration.
- The specific role of MMP-9 in the innate immune response to bacterial peritonitis remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of MMP-9 in the host defense against Escherichia coli-induced peritonitis.
- To determine the impact of MMP-9 deficiency on bacterial clearance, immune cell recruitment, and organ damage.
Main Methods:
- Utilized gene-deficient (MMP-9(-/-)) and wild-type mice infected intraperitoneally with Escherichia coli.
- Quantified MMP-9 mRNA and protein levels.
- Assessed bacterial outgrowth, dissemination, cytokine and chemokine responses, leukocyte recruitment, and distant organ damage.
Main Results:
- MMP-9(-/-) mice exhibited reduced resistance to E. coli peritonitis, with increased bacterial outgrowth and dissemination.
- Leukocyte recruitment to the infection site was impaired in MMP-9(-/-) mice despite elevated local chemokine levels.
- MMP-9 deficiency led to more severe distant organ damage during infection.
Conclusions:
- MMP-9 is essential for an effective innate immune response to E. coli peritonitis.
- MMP-9 contributes to controlling bacterial infection by facilitating leukocyte migration and limiting tissue damage.
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