Stolen Craig M, Marttila-Ichihara Fumiko, Koskinen Kaisa, Yegutkin Gennady G, Turja Raisa, Bono Petri, Skurnik Mikael, Hänninen Arno, Jalkanen Sirpa, Salmi Marko
Department of Medical Microbiology, MediCity Research Laboratory, National Public Health Institute, Turku University, 20520 Turku, Finland.
Immunity. 2005 Jan;22(1):105-15. doi: 10.1016/j.immuni.2004.12.006.
Leukocyte migration from the blood to tissues is a prerequisite for normal immune responses. We produced mice deficient in an endothelial cell-surface oxidase (amine oxidase, copper containing-3 [AOC3], also known as vascular adhesion protein-1 [VAP-1]) and found that this enzyme is needed for leukocyte extravasation in vivo. Real-time imaging shows that AOC3 mediates slow rolling, firm adhesion, and transmigration of leukocytes in vessels at inflammatory sites and lymphoid tissues. Absence of AOC3 results in reduced lymphocyte homing into lymphoid organs and in attenuated inflammatory response in peritonitis. These data alter the paradigm of leukocyte extravasation cascade by providing the first physiological proof for the concept that endothelial cell surface enzymes regulate the development of inflammatory reactions in vivo and suggest that this enzyme should be useful as an anti-inflammatory target.
白细胞从血液迁移到组织是正常免疫反应的前提条件。我们培育出了缺乏一种内皮细胞表面氧化酶（含铜胺氧化酶3 [AOC3]，也称为血管黏附蛋白-1 [VAP-1]）的小鼠，并发现这种酶是体内白细胞渗出所必需的。实时成像显示，AOC3介导炎症部位和淋巴组织血管中白细胞的缓慢滚动、牢固黏附和迁移。缺乏AOC3会导致淋巴细胞归巢至淋巴器官的能力下降，以及腹膜炎炎症反应减弱。这些数据通过为内皮细胞表面酶在体内调节炎症反应发展这一概念提供首个生理学证据，改变了白细胞渗出级联反应的范式，并表明这种酶有望成为一个抗炎靶点。
