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Updated: Jun 5, 2026

Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
ADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation
Geneviève Paulissen1, Natacha Rocks, Maud M Guéders
1Laboratory of Tumor and Development Biology, GIGA-Research (GIGA-I3 and GIGA-cancer), University of Liege and CHU of Liege, Sart-Tilman, Belgium.
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.
Insights
A disintegrin and metalloproteinase-8 (ADAM-8) promotes allergen-induced airway inflammation by increasing dendritic cell (DC) recruitment and chemokine production. Inhibiting ADAM-8 reduces inflammation in a mouse asthma model.
Area of Science:
- Immunology
- Respiratory Medicine
- Molecular Biology
Background:
- Asthma involves complex inflammatory pathways, with proteinases playing a key role.
- A disintegrin and metalloproteinases (ADAMs) are implicated in inflammatory processes.
- ADAM-8's specific role in allergic airway inflammation requires further investigation.
Purpose of the Study:
- To investigate the expression and function of ADAM-8 in a mouse model of allergen-induced airway inflammation.
- To determine the impact of ADAM-8 inhibition on inflammatory cell recruitment and mediator production.
Main Methods:
- Utilized a mouse model of allergen-induced airway inflammation.
- Assessed ADAM-8 expression in lung tissue and isolated dendritic cells (DCs).
- Employed anti-ADAM-8 antibody treatment and ADAM-8 knockout mice (ADAM-8(-/-)) to evaluate functional roles.
- Quantified inflammatory cells in bronchoalveolar lavage fluid (BALF) and peribronchial areas.
- Measured levels of chemokines CCL11 and CCL22.
Main Results:
- ADAM-8 expression was significantly increased in the lungs of allergen-exposed mice.
- Treatment with anti-ADAM-8 antibody or using ADAM-8(-/-) mice reduced acute airway inflammation.
- ADAM-8 depletion led to a significant decrease in CD11c(+) lung dendritic cells (DCs).
- Lower levels of CCL11 and CCL22 were observed in mice with reduced ADAM-8 activity.
Conclusions:
- ADAM-8 promotes allergen-induced acute airway inflammation.
- ADAM-8 appears to facilitate inflammation by enhancing DC recruitment and the production of CCL11 and CCL22.
- Targeting ADAM-8 may represent a therapeutic strategy for allergic airway diseases.
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