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Role of A Disintegrin And Metalloprotease-12 in Neutrophil Recruitment Induced by Airway Epithelium
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Role of A Disintegrin And Metalloprotease-12 in Neutrophil Recruitment Induced by Airway Epithelium
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Role of A Disintegrin And Metalloprotease-12 in Neutrophil Recruitment Induced by Airway Epithelium
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Journal Article
Role of A Disintegrin And Metalloprotease-12 in Neutrophil Recruitment Induced by Airway Epithelium
2009
Overview
Abstract
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-α 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 α3 and α4 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.
Publisher
Am Thoracic Soc,Oxford University Press,American Thoracic Society
Subject
/ ADAM-12
/ allergy
/ Biochemistry, biophysics & molecular biology
/ Biochimie, biophysique & biologie moléculaire
/ Cells, Cultured - enzymology
/ Chemotaxis, Leukocyte - physiology
/ Epithelial Cells - enzymology
/ Humans
/ Membrane Proteins - genetics
/ Membrane Proteins - physiology
/ Receptor, Epidermal Growth Factor - physiology
/ Recombinant Fusion Proteins - physiology
/ Rhinitis
/ Rhinitis, Allergic, Perennial - pathology
/ Rhinitis, Allergic, Seasonal - pathology
