Inhibition of Matrix Metalloproteinases Prevents Allergen-Induced Airway Inflammation in a Murine Model of Asthma
| Autor: | K, Kumagai, I, Ohno, S, Okada, Y, Ohkawara, K, Suzuki, T, Shinya, H, Nagase, K, Iwata, K, Shirato |
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| Rok vydání: | 1999 |
| Předmět: |
CD3 Complex
Ovalbumin Immunology Matrix Metalloproteinase Inhibitors Leukocyte Count Mice Administration Inhalation Animals Humans Immunology and Allergy Collagenases Lung Inflammation Mice Inbred BALB C Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinase-1 Metalloendopeptidases Allergens Asthma Recombinant Proteins Eosinophils Trachea Disease Models Animal Matrix Metalloproteinase 9 Gelatinases Matrix Metalloproteinase 2 Female Interleukin-5 Bronchoalveolar Lavage Fluid Protein Binding |
| Zdroj: | The Journal of Immunology. 162:4212-4219 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.162.7.4212 |
| Popis: | Although matrix metalloproteinases (MMPs) have been reported to play crucial roles in the migration of inflammatory cells through basement membrane components in vitro, the role of MMPs in the in vivo accumulation of the cells to the site of inflammation in bronchial asthma is still obscure. In this study, we investigated the role of MMPs in the pathogenesis of bronchial asthma, using a murine model of allergic asthma. In this model, we observed the increase of the release of MMP-2 and MMP-9 in bronchoalveolar lavage fluids after Ag inhalation in the mice sensitized with OVA, which was accompanied by the infiltration of lymphocytes and eosinophils. Administration of tissue inhibitor of metalloproteinase-2 to airways inhibited the Ag-induced infiltration of lymphocytes and eosinophils to airway wall and lumen, reduced Ag-induced airway hyperresponsiveness, and increased the numbers of eosinophils and lymphocytes in peripheral blood. The inhibition of cellular infiltration to airway lumen was observed also with tissue inhibitor of metalloproteinase-1 and a synthetic matrix metalloproteinase inhibitor. These data suggest that MMPs, especially MMP-2 and MMP-9, are crucial for the infiltration of inflammatory cells and the induction of airway hyperresponsiveness, which are pathophysiologic features of bronchial asthma, and further raise the possibility of the inhibition of MMPs as a therapeutic strategy of bronchial asthma. |
| Databáze: | OpenAIRE |
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