Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/3269
Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation
English
Cataldo, Didier[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path. >]
Munaut, Carine[Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Foidart, Jean-Michel[Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement >]
Louis, Renaud[Université de Liège - ULg > Département des sciences cliniques > Pneumologie - Allergologie]
Noël, Agnès[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
[en] 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 allergenexposure.