Potential key role of ADAM28 in airway remodeling following eosinophilic airway inflammation
G. Bendavid (1) (2), N. Rocks (2), P. Lefebvre (1), D. Cataldo (2) (3)
(1) ENT department, University Hospital of Liege, Belgium
(2) Laboratory of Tumor and Development Biology, GIGA-Research, University of Liege (ULiege), Belgium (3) Respiratory diseases department, University Hospital of Liege (CHU), Belgium
Introduction and aim:
Patients suffering from allergy may display an eosinophilic inflammation of the airways. A Disintegrin And Metalloproteinase (ADAM) might play important roles in allergic
inflammatory processes since they are able to cleave various modulators of inflammation. ADAM28 is expressed by epithelial cells in human tissues. ADAM28 influences lymphocyte adhesion and migration.
The aim of our research is to study the potential role of ADAM28 in eosinophilic airway inflammation.
Material and methods:
Human study: ADAM28 expression was quantified in nasal polyps from atopic patients and in sputum from asthmatics and compared with ADAM28 levels in healthy subjects.
Mouse study: A pulmonary allergic inflammation (ovalbumin (OVA) sensitization) was induced in BALB/c, ADAM28 knock-out (KO) and corresponding wild-type (WT). After ovalbumin exposure, ADAM28 expression was measured in lung tissues by RTPCR. Airway resistances were measured by using Flexivent®. Lung remodeling was evaluated using immunohistochemical staining. The numbers of inflammatory cells were analyzed in lung using fluorescence-activated cell sorting. Airway Inflammation was also evaluated using a staining-score.
Results:
ADAM28 expression was increased in nasal polyps from atopic patients as compared to controls. ADAM28 was also overexpressed in sputum from patients displaying asthma versus healthy subjects. In mice, ADAM28 expression was increased in lung parenchyma after OVA exposure. Interestingly, after OVA exposure, ADAM28 deficient mice recruited less activated lymphocytes in the airways and airway remodeling was decreased. This was accompanied by a significant decrease in airway resistance in KO animals.
Conclusions:
ADAM28 could play a key role in airway remodeling in the context of allergen-induced tissue eosinophilia.