Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma

KY Vermaelen, D Cataldo, K Tournoy… - The Journal of …, 2003 - journals.aai.org
KY Vermaelen, D Cataldo, K Tournoy, T Maes, A Dhulst, R Louis, JM Foidart, A Noël
The Journal of Immunology, 2003journals.aai.org
Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including
asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory
leukocytes across basement membranes. This study investigated the role of MMP-9 in
airway DC trafficking during allergen-induced airway inflammation. MMP-9 gene deletion
affected the trafficking of pulmonary DCs in a specific way: only the inflammatory
transmigration of DCs into the airway lumen was impaired, whereas DC-mediated transport …
Abstract
Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory leukocytes across basement membranes. This study investigated the role of MMP-9 in airway DC trafficking during allergen-induced airway inflammation. MMP-9 gene deletion affected the trafficking of pulmonary DCs in a specific way: only the inflammatory transmigration of DCs into the airway lumen was impaired, whereas DC-mediated transport of airway Ag to the thoracic lymph nodes remained unaffected. In parallel, the local production of the Th2-attracting chemokine CC chemokine ligand 17/thymus and activation-regulated chemokine, which was highly concentrated in purified lung DCs, fell short in the airways of allergen-exposed MMP-9−/− mice. This was accompanied by markedly reduced peribronchial eosinophilic infiltrates and impaired allergen-specific IgE production. We conclude that the specific absence of MMP-9 activity inhibits the development of allergic airway inflammation by impairing the recruitment of DCs into the airways and the local production of DC-derived proallergic chemokines.
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