Matrix metalloproteinase-9 deficiency results in enhanced allergen-induced airway inflammation.
Matrix metalloproteinases (MMPs) are a large family of endopeptidases that proteolytically degrade extracellular matrix. Many different cells produce MMP-9, and levels have been shown to be up-regulated in patients with allergic asthma. The aim of this study was to investigate the in vivo role of MMP-9 during allergen-induced airway inflammation. Acute allergic pulmonary eosinophilia was established in MMP-9 knockout (KO) and wild-type (WT) control mice by sensitization and challenge with OVA. Cell recruitment was significantly increased in both bronchoalveolar lavage (BAL) and lung tissue compartments in MMP-9 KO mice compared with WT mice. This heightened cell recruitment was primarily due to increased eosinophils and Th2 cells in the BAL and lung tissue of MMP-9 KO mice in comparison with WT controls. Moreover, levels of the Th2 cytokines, IL-4 and IL-13, and the chemokines eotaxin/CCL11 and macrophage-derived chemokine/CCL22 were substantially increased in MMP-9 KO mice compared with WT after OVA challenge. Resolution of eosinophilia was similar between MMP-9 KO and WT mice, but Th2 cells persisted in BAL and lungs of MMP-9 KO mice for longer than in WT mice. Our results indicate that MMP-9 is critically involved in the recruitment of eosinophils and Th2 cells to the lung following allergen challenge, and suggest that MMP-9 plays a role in the development of Th2 responses to allergen.
McMillan
Sarah J
SJ
Division of Biomedical Sciences, Faculty of Medicine Imperial College, London, United Kingdom.
Kearley
Jennifer
J
Campbell
J Darren
JD
Zhu
Xing-Wu
XW
Larbi
Karen Y
KY
Shipley
J Michael
JM
Senior
Robert M
RM
Nourshargh
Sussan
S
Lloyd
Clare M
CM
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000485:Allergens; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin; D020780:Matrix Metalloproteinase 9