1. ADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation.
- Author
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Paulissen G, Rocks N, Guéders MM, Bedoret D, Crahay C, Quesada-Calvo F, Hacha J, Bekaert S, Desmet C, Foidart JM, Bureau F, Noel A, and Cataldo DD
- Subjects
- ADAM Proteins antagonists & inhibitors, ADAM Proteins genetics, ADAM Proteins immunology, Animals, Antibodies immunology, Antibodies pharmacology, Antibodies therapeutic use, Antigens, CD genetics, Antigens, CD immunology, Asthma immunology, Asthma pathology, Bronchoalveolar Lavage Fluid cytology, Cell Count, Cell Movement genetics, Cell Movement immunology, Chemokine CCL11 metabolism, Chemokine CCL22 metabolism, Cytokines metabolism, Eosinophils metabolism, Eosinophils pathology, Gene Expression genetics, Inflammation immunology, Inflammation metabolism, Inflammation pathology, Inflammation prevention & control, Lung drug effects, Lung metabolism, Lung pathology, Macrophages, Alveolar metabolism, Macrophages, Alveolar pathology, Male, Membrane Proteins antagonists & inhibitors, Membrane Proteins genetics, Membrane Proteins immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Ovalbumin immunology, Vaccination, ADAM Proteins metabolism, Antigens, CD metabolism, Asthma metabolism, Membrane Proteins metabolism
- Abstract
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 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 DC 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 knockout 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 DC. We also report lower levels of CCL11 and CCL22 production in antibody-treated mice and ADAM-8- deficient mice that might be explained by decreased eosinophilic inflammation and lower numbers of DC, respectively. In conclusion, ADAM-8 appears to favour allergen-induced acute airway inflammation by promoting DC recruitment and CCL11 and CCL22 production., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2011
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