Role of A Disintegrin and Metalloprotease-12 in Neutrophil Recruitment Induced by Airway Epithelium.
Rocks, Natacha ; ; Paulissen, Geneviève et al
in American Journal of Respiratory Cell and Molecular Biology (2009), 41(4), 449-58
Among proteases, metalloproteases are implicated in tissue remodeling, as shown in numerous diseases including allergy. ADAMs (A Disintegrin And Metalloprotease) metalloproteases are implicated in ... [more ▼]
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. [less ▲]Detailed reference viewed: 61 (7 ULg)
L'asthme: une maladie de tout l'arbre aerien.
; Louis, Renaud ; et al
in Revue des Maladies Respiratoires (2009), 26(8), 851-8
Inflammation and remodelling are constant features of asthma. They are present throughout the whole bronchial tree, even in the small airways (less than 2 mm). The inflammatory cell infiltrate and ... [more ▼]
Inflammation and remodelling are constant features of asthma. They are present throughout the whole bronchial tree, even in the small airways (less than 2 mm). The inflammatory cell infiltrate and structural changes are, in most cases, identical. However, in severe asthma, nocturnal asthma and fatal asthma, the cellular infiltrate in the distal airways is more intense and the number of activated cells is increased. In fatal asthma there are major alterations in the distal airways involving the smooth muscle and the bronchial epithelium, and mucus hypersecretion leading to distal airway plugging. Thus the histopathological changes in the distal airways contribute to the most severe stages of asthma and should be targeted by treatment. Currently the non-invasive tools that reflect inflammation are unable to assess these changes in the distal airways. [less ▲]Detailed reference viewed: 42 (5 ULg)