title: Role of A disintegrin and metalloprotease-12 in neutrophil recruitment induced by airway epithelium.
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-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.
authors.affiliation: INSERM U774, Biomolecules and Pulmonary Inflammation, Institut Pasteur de Lille, 1 rue du Pr Calmette, BP245, 59019 Lille Cedex, France.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Estrella
authors.forename: Natacha
authors.initials: N
authors.lastname: Rocks
authors.forename: Geneviève
authors.initials: G
authors.lastname: Paulissen
authors.forename: Florence
authors.initials: F
authors.lastname: Quesada-Calvo
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Eva
authors.initials: E
authors.lastname: Vilain
authors.forename: Philippe
authors.initials: P
authors.lastname: Lassalle
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tillie-Leblond
authors.forename: Didier
authors.initials: D
authors.lastname: Cataldo
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000072199:ADAM12 Protein; D000485:Allergens / Q000494:pharmacology; D001980:Bronchi / Q000473:pathology*; D051928:CD47 Antigen / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion; D002478:Cells, Cultured / Q000201:enzymology / Q000473:pathology; D054360:Chemokine CXCL1 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004847:Epithelial Cells / Q000201:enzymology; D066246:ErbB Receptors / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012221:Rhinitis, Allergic, Perennial / Q000473:pathology*; D006255:Rhinitis, Allergic, Seasonal / Q000473:pathology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000485:Allergens; D051928:CD47 Antigen; C497894:CD47 protein, human; D054360:Chemokine CXCL1; D016023:Integrins; D016209:Interleukin-8; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human