ADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation

Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A Disintegrin And Metalloproteinases (ADAMs) displaying the ability to cleave membrane-bound mediators or cytokines appear to be key mediators in various inflammatory processes. In the present study, we have investigated ADAM-8 expression and production in a mouse model of allergen-induced airway inflammation. In allergen-exposed animals, increased expression of ADAM-8 was found in the lung parenchyma and in dendritic cells purified from the lungs. The potential role of ADAM-8 in the development of allergen-induced airway inflammation was further investigated by the use of an anti-ADAM-8 antibody and ADAM-8 knock-out animals. We observed a decrease in allergen-induced acute inflammation both in BALF and the peribronchial area in anti-ADAM-8 antibody-treated mice and in ADAM-8 deficient mice (ADAM-8-/-) after allergen exposure. ADAM-8 depletion led to a significant decrease of the CD11c+ lung dendritic cells. We also report lower levels of CCL11 and CCL22 production in antibody-treated mice and ADAM-8-/- mice that might be explained by decreased eosinophilic inflammation and lower numbers of dendritic cells, respectively. In conclusion, ADAM-8 appears to favour allergen-induced acute airway inflammation by promoting dendritic cell recruitment and CCL11 and CCL22 production