Role of ADAM8 in experimental asthma.
A disintegrin and metalloprotease (ADAM) family members, characterized by a metalloprotease and a disintegrin domain, are membrane-anchored glycoproteins involved in proteolysis and cell adhesion. ADAM8 is specifically induced in the experimental murine asthmatic lung. To evaluate novel pathways involved in asthma pathogenesis, using ADAM8 transgenic mice (ATMS2) in a murine model of asthma. Massive cellular infiltrates in peribronchovascular and interstitial lesions were observed in control mice, while in ATMS2 mice there were only occasional. Vascular cell adhesion molecule (VCAM-1) is involved in specific eosinophil adhesions via alpha4beta1 integrin. VCAM-1 shedding was mediated by the ADAM8 metalloprotease. Endothelial cell shedding of VCAM-1 was increased in ATMS2-stimulated human umbilical endothelial cells. ADAM8-mediated shedding of VCAM-1 might be important for the suppression of experimental asthma. Our data suggest that ADAM8 is a useful therapeutic target.
Matsuno
Osamu
O
Division of Pulmonary Medicine, Department of Brain and Nerve Science, Oita University Faculty of Medicine, Hasama-machi, Oita 879-5593, Japan. matsuno@med.oita-u.ac.jp
Miyazaki
Eishi
E
Nureki
Shinichi
S
Ueno
Takuya
T
Kumamoto
Toshihide
T
Higuchi
Yasunori
Y
D051722:ADAM Proteins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism* / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014470:Umbilical Cord / Q000187:drug effects / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4; D051722:ADAM Proteins; C489402:Adam8 protein, mouse