Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation.
Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has recently been reported to be increased in the bronchoalveolar lavage fluid (BALF) from asthmatic patients. To evaluate the role of MMP-8 in asthma, we measured MMP-8 expression in lung tissue in an OVA-sensitized mouse model of asthma and addressed the effect of MMP-8 deletion on allergen-induced bronchial inflammation. MMP-8 production was increased in lungs from C57BL/6 mice exposed to allergens. After allergen exposure, MMP-8(-/-) mice developed an airway inflammation characterized by an increased neutrophilic inflammation in BALF and an increased neutrophilic and eosinophilic infiltration in the airway walls. MMP-8 deficiency was associated with increased levels of IL-4 and anti-OVA IgE and IgG1 in BALF and serum, respectively. Although allergen exposure induced an enhancement of LPS-induced CXC chemokine, KC, and MIP-2 levels in BALF and lung parenchyma, no difference was observed between the two genotypes. Inflammatory cell apoptosis was reduced in the lungs from MMP-8(-/-) mice. For the first time, our study evidences an important role of MMP-8 in the control of neutrophilic and eosinophilic infiltration during allergen-induced lung inflammation, and demonstrates that the anti-inflammatory effect of MMP-8 is partly due to a regulation of inflammatory cell apoptosis.
Gueders
Maud M
MM
Department of Pneumology, Center for Biomedical Integrative Genoproteomic, University of Liege, Belgium.
Balbin
Milagros
M
Rocks
Natacha
N
Foidart
Jean-Michel
JM
Gosset
Philippe
P
Louis
Renaud
R
Shapiro
Steven
S
Lopez-Otin
Carlos
C
Noël
Agnes
A
Cataldo
Didier D
DD
D000485:Allergens / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D001980:Bronchi / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D014020:Tissue Extracts / Q000737:chemistry / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D018836:Inflammation Mediators; D014020:Tissue Extracts; D010047:Ovalbumin; D020784:Matrix Metalloproteinase 8