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Gelatinase B/matrix metalloproteinase-9 contributes to cellular infiltration in a murine model of zymosan peritonitis.
- Source :
-
Immunobiology [Immunobiology] 2006; Vol. 211 (3), pp. 137-48. Date of Electronic Publication: 2006 Feb 03. - Publication Year :
- 2006
-
Abstract
- Murine zymosan-induced peritonitis represents a well-defined model of acute inflammation. However, the molecular mechanisms by which leukocytes degrade basement membranes during extravasation into the peritoneum are not clear. Gelatinase B (MMP-9) is thought to participate in cellular migration, yet its role in leukocyte transmigration through endothelia during inflammation remains controversial. The aim of the present study was to evaluate the role of MMP-9 in the cell influx during zymosan-induced experimental peritonitis. In zymosan-treated Balb/c mice MMP-9 and its natural inhibitor (tissue inhibitor of metalloproteinase 1 - TIMP-1) were present in the peritoneal fluid and plasma at the time of peritoneal neutrophil (polymorphonuclear leukocyte - PMN) infiltration and persisted there until the time of monocytes/macrophages influx. To probe the function of gelatinases, gelatinase B-deficient mice (MMP-9(-/-)) were used as well as Balb/c mice treated with cyclic CTTHWGFTLC (INH), a specific peptide inhibitor of gelatinases. The studies revealed that in either group of mice deprived of MMP-9 activity, PMN infiltration was impaired at the time of their maximal extravasation (6h) while tumor necrosis factor alpha (TNF-alpha), cytokine-induced neutrophil chemoattractant (KC) and interleukin 10 (IL-10) levels were not changed. At later stages (24 h post-zymosan) a significant increase in PMNs was observed in MMP-9(-/-) mice, but not in the inhibitor-treated mice, in comparison to their respective controls. Moreover, intraperitoneal (i.p.) injection of recombinant mouse pro-MMP-9 induced leukocyte accumulation in peritoneum. Collectively, the findings indicate that gelatinase B participates in leukocyte transmigration; however, its function can be compensated by other mechanisms.
- Subjects :
- Animals
Chemokines metabolism
Disease Models, Animal
Enzyme Precursors administration & dosage
Enzyme Precursors genetics
Enzyme Precursors physiology
Male
Matrix Metalloproteinase 9 administration & dosage
Matrix Metalloproteinase 9 genetics
Matrix Metalloproteinase Inhibitors
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Peritonitis pathology
Recombinant Proteins administration & dosage
Recombinant Proteins genetics
Recombinant Proteins metabolism
Tissue Inhibitor of Metalloproteinase-1 metabolism
Cell Movement drug effects
Cell Movement physiology
Matrix Metalloproteinase 9 physiology
Neutrophils enzymology
Neutrophils pathology
Peritonitis chemically induced
Peritonitis enzymology
Zymosan toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0171-2985
- Volume :
- 211
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Immunobiology
- Publication Type :
- Academic Journal
- Accession number :
- 16530081
- Full Text :
- https://doi.org/10.1016/j.imbio.2005.08.004