Role of A Disintegrin And Metalloprotease-12 in Neutrophil Recruitment Induced by Airway Epithelium

• Published in: American journal of respiratory cell and molecular biology Vol. 41; no. 4; pp. 449 - 458
• Main Authors: Estrella, Cecilia, Rocks, Natacha, Paulissen, Genevieve, Quesada-Calvo, Florence, Noel, Agnes, Vilain, Eva, Lassalle, Philippe, Tillie-Leblond, Isabelle, Cataldo, Didier, Gosset, Philippe
• Format: Journal Article Web Resource
• Language: English
• Published: United States Am Thoracic Soc 01.10.2009; American Thoracic Society
• Subjects: ADAM Proteins - genetics; ADAM Proteins - physiology; ADAM-12; ADAM12 Protein; airway epithelial cell; Allergens - pharmacology; allergy; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Bronchi - pathology; CD47 Antigen - biosynthesis; CD47 Antigen - genetics; Cell Adhesion; Cells, Cultured - enzymology; Cells, Cultured - pathology; Chemokine CXCL1 - secretion; Chemotaxis, Leukocyte - physiology; Epithelial Cells - enzymology; Gene Expression Regulation; Humans; inflammation; Integrins - biosynthesis; Integrins - genetics; Interleukin-8 - secretion; Life sciences; Membrane Proteins - genetics; Membrane Proteins - physiology; neutrophil; Neutrophils - physiology; Receptor, Epidermal Growth Factor - physiology; Recombinant Fusion Proteins - physiology; Rhinitis, Allergic, Perennial - pathology; Rhinitis, Allergic, Seasonal - pathology; Sciences du vivant; Transfection; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1044-1549; 1535-4989; 1535-4989
• DOI: 10.1165/rcmb.2008-0124OC

Among proteases, metalloproteases are implicated in tissue remodeling, as shown in numerous diseases including allergy. ADAMs (A Disintegrin And Metalloprotease) metalloproteases are implicated in physiologic processes such as cytokine and growth factor shedding, cell migration, adhesion, or repulsion. Our aim was to measure ADAM-12 expression in airway epithelium and to define its role during the allergic response. To raise this question, we analyzed the ADAM-12 expression ex vivo after allergen exposure in patients with allergic rhinitis and in vitro in cultured primary human airway epithelial cells (AEC). Clones of BEAS-2B cells transfected with the full-length form of ADAM-12 were generated to study the consequences of ADAM-12 up-regulation on AEC function. After allergen challenge, a strong increase of ADAM-12 expression was observed in airway epithelium from patients with allergic rhinitis but not from control subjects. In contrast with the other HB-epidermal growth factor sheddases, ADAM-10 and -17, TNF-alpha in vitro increased the expression of ADAM-12 by AEC, an effect amplified by IL-4 and IL-13. Up-regulation of ADAM-12 in AEC increased the expression of alpha3 and alpha4 integrins and to the modulation of cell migration on fibronectin but not on collagen. Moreover, overexpression of ADAM-12 in BEAS-2B enhanced the secretion of CXCL1 and CXCL8 and their capacity to recruit neutrophils. CD47 was strongly decreased by ADAM-12 overexpression, a process associated with a reduced adhesion of neutrophils. These effects were mainly dependent on epidermal growth factor receptor activation. In summary, ADAM-12 is produced during allergic reaction by AEC and might increase neutrophil recruitment within airway mucosa.