Aurrand-Lions Michel, Lamagna Chrystelle, Dangerfield John P, Wang Shijun, Herrera Pedro, Nourshargh Sussan, Imhof Beat A
Department of Pathology and Immunology, Medical University Center, Geneva, Switzerland.
J Immunol. 2005 May 15;174(10):6406-15. doi: 10.4049/jimmunol.174.10.6406.
Leukocyte recruitment from blood to inflammatory sites occurs in a multistep process that involves discrete molecular interactions between circulating and endothelial cells. Junctional adhesion molecule (JAM)-C is expressed at different levels on endothelial cells of lymphoid organs and peripheral tissues and has been proposed to regulate neutrophil migration by its interaction with the leukocyte integrin Mac-1. In the present study, we show that the accumulation of leukocytes in alveoli during acute pulmonary inflammation in mice is partially blocked using neutralizing Abs against JAM-C. To confirm the function of JAM-C in regulating leukocyte migration in vivo, we then generated a strain of transgenic mice overexpressing JAM-C under the control of the endothelial specific promotor Tie2. The transgenic animals accumulate more leukocytes to inflammatory sites compared with littermate control mice. Intravital microscopy shows that this is the result of increased leukocyte adhesion and transmigration, whereas rolling of leukocytes is not significantly affected in transgenic mice compared with littermates. Thus, JAM-C participates in the later steps of the leukoendothelial adhesion cascade.
白细胞从血液募集到炎症部位的过程分多个步骤进行，涉及循环细胞与内皮细胞之间离散的分子相互作用。连接黏附分子（JAM）-C在淋巴器官和外周组织的内皮细胞上有不同程度的表达，有人提出它通过与白细胞整合素Mac-1相互作用来调节中性粒细胞迁移。在本研究中，我们发现，使用抗JAM-C的中和抗体可部分阻断小鼠急性肺部炎症期间肺泡中白细胞的积聚。为了证实JAM-C在体内调节白细胞迁移的功能，我们随后构建了一种在内皮细胞特异性启动子Tie2控制下过表达JAM-C的转基因小鼠品系。与同窝对照小鼠相比，转基因动物在炎症部位积聚了更多白细胞。活体显微镜检查显示，这是白细胞黏附和迁移增加的结果，而与同窝小鼠相比，转基因小鼠中白细胞的滚动未受到显著影响。因此，JAM-C参与了白细胞-内皮细胞黏附级联反应的后期步骤。
