Matrix Metalloproteinase-9 Deficiency Impairs Cellular Infiltration and Bronchial Hyperresponsiveness during Allergen-Induced Airway Inflammation

• Published in: The American journal of pathology Vol. 161; no. 2; pp. 491 - 498
• Main Authors: Cataldo, Didier D., Tournoy, Kurt G., Vermaelen, Karim, Munaut, Carine, Foidart, Jean-Michel, Louis, Renaud, Noël, Agnès, Pauwels, Romain A.
• Format: Journal Article Web Resource
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.08.2002; ASIP; American Society for Investigative Pathology
• Subjects: Allergens - immunology; Allergic diseases; Animals; Asthma - genetics; Asthma - metabolism; Asthma - pathology; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biological and medical sciences; Cell Movement - genetics; Chronic obstructive pulmonary disease, asthma; Immunopathology; Leukocytes, Mononuclear - pathology; Life sciences; Matrix Metalloproteinase 9 - deficiency; Matrix Metalloproteinase 9 - genetics; Medical sciences; Mice; Mice, Knockout; Ovalbumin - administration & dosage; Ovalbumin - immunology; Pneumology; Regular; Respiratory and ent allergic diseases; Sciences du vivant; Immunopathology; Allergy; Biochemical analysis; Respiratory disease; Enzyme; Pathogenesis; Deficiency; Rodentia; Metalloendopeptidases; Gelatinase B; Asthma; Peptidases; Pathology; Vertebrata; Infiltrate; Experimental disease; Mammalia; Mononuclear cell; Mouse; Bronchoalveolar lavage; Animal; Hydrolases; Obstructive pulmonary disease; Molecular biology
• ISSN: 0002-9440; 1525-2191; 1525-2191
• DOI: 10.1016/S0002-9440(10)64205-8

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.