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 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.
Laboratory of Tumor and Development Biology, GIGA-Research (GIGA-I3 and GIGA-cancer), University of Liege and CHU of Liege, Sart-Tilman, Belgium.
Geneviève
G
Paulissen
Natacha
N
Rocks
Maud M
MM
Guéders
Denis
D
Bedoret
Céline
C
Crahay
Florence
F
Quesada-Calvo
Jonathan
J
Hacha
Sandrine
S
Bekaert
Christophe
C
Desmet
Jean-Michel
JM
Foidart
Fabrice
F
Bureau
Agnès
A
Noel
Didier D
DD
Cataldo
D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D054413:Chemokine CCL11 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D014611:Vaccination
D000906:Antibodies; D015703:Antigens, CD; C515457:Ccl11 protein, mouse; C515483:Ccl22 protein, mouse; D054413:Chemokine CCL11; D054422:Chemokine CCL22; D016207:Cytokines; D008565:Membrane Proteins; D010047:Ovalbumin; D051722:ADAM Proteins; C489402:Adam8 protein, mouse