Matsuno Osamu, Miyazaki Eishi, Nureki Shinichi, Ueno Takuya, Kumamoto Toshihide, Higuchi Yasunori
Division of Pulmonary Medicine, Department of Brain and Nerve Science, Oita University Faculty of Medicine, Hasama-machi, Oita 879-5593, Japan.
Immunol Lett. 2006 Jan 15;102(1):67-73. doi: 10.1016/j.imlet.2005.07.006. Epub 2005 Aug 2.
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.
解聚素和金属蛋白酶（ADAM）家族成员的特征是具有金属蛋白酶和解聚素结构域，它们是参与蛋白水解和细胞黏附的膜锚定糖蛋白。ADAM8在实验性小鼠哮喘肺中特异性诱导表达。为了评估哮喘发病机制中涉及的新途径，我们在小鼠哮喘模型中使用了ADAM8转基因小鼠（ATMS2）。在对照小鼠中观察到支气管血管周围和间质病变中有大量细胞浸润，而在ATMS2小鼠中则只有偶尔的浸润。血管细胞黏附分子（VCAM-1）通过α4β1整合素参与特异性嗜酸性粒细胞黏附。VCAM-1的脱落由ADAM8金属蛋白酶介导。在ATMS2刺激的人脐静脉内皮细胞中，VCAM-1的内皮细胞脱落增加。ADAM8介导的VCAM-1脱落可能对实验性哮喘的抑制很重要。我们的数据表明ADAM8是一个有用的治疗靶点。
