Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation.
We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and their corresponding wild-type (WT) littermates. After a single intraperitoneal sensitization to ovalbumin, the mice were exposed daily either to ovalbumin (1%) or phosphate-buffered saline aerosols from days 14 to 21. Significantly less peribronchial mononuclear cell infiltration of the airways and less lymphocytes in the bronchoalveolar lavage fluid were detected in challenged MMP-9(-/-) as compared to WT mice. In contrast, comparable numbers of bronchoalveolar lavage fluid eosinophils were observed in both genotypes. After allergen exposure, the WT mice developed a significant airway hyperresponsiveness to carbachol whereas the MMP-9(-/-) mice failed to do so. Allergen exposure induced an increase of MMP-9-related gelatinolytic activity in WT lung extracts. Quantitative reverse transcriptase-polymerase chain reaction showed increased mRNA levels of MMP-12, MMP-14, and urokinase-type plasminogen activator after allergen exposure in the lung extracts of WT mice but not in MMP-9-deficient mice. In contrast, the expression of tissue inhibitor of metalloproteinases-1 was enhanced after allergen exposure in both groups. We conclude that MMP-9 plays a key role in the development of airway inflammation after allergen exposure.
Cataldo
Didier D
DD
Department of Respiratory Diseases and Laboratory of Biology of Tumours and Development, University of Liege, Liege, Belgium. didier.cataldo@ulg.ac.be
Tournoy
Kurt G
KG
Vermaelen
Karim
K
Munaut
Carine
C
Foidart
Jean-Michel
JM
Louis
Renaud
R
Noël
Agnès
A
Pauwels
Romain A
RA
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
D000485:Allergens; D010047:Ovalbumin; D020780:Matrix Metalloproteinase 9