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    • 5. 发明申请
    • JAM-1 as ligand of the beta-2 integrin LFA-1
    • JAM-1作为β-2整合素LFA-1的配体
    • US20050025776A1
    • 2005-02-03
    • US10411397
    • 2003-04-11
    • Christian Weber
    • Christian Weber
    • A61K38/17A61K48/00C07K14/705G01N33/50A61K39/00
    • A61K38/1709A61K48/00C07K14/705G01N33/505
    • Inflammatory recruitment of leukocytes is governed by dynamic interactions of integrins with endothelial immunglobulin superfamily (IgSF) proteins. We have identified the IgSF member junctional adhesion molecule-1 (JAM-1) as a ligand of the β2 integrin lymphocyte function-associated antigen-1 (LFA-1). Under static and physiologic flow conditions, JAM-1 contributed to LFA-1-dependent transendothelial migration of T cells and neutrophils, and also to LFA-1-mediated arrest of T cells triggered by chemokines on endothelium co-stimulated with cytokines to re-distribute JAM-1 from the tight junctions. Transfectants expressing JAM-1 supported LFA-1-mediated adhesion of leukocytes which required the membrane-proximal Ig-like domain 2 of JAM-1. Thus, JAM-1 is a counter-receptor for LFA-1 ideally situated to guide and control transmigration during leukocyte recruitment.
    • 白细胞的炎症征募由整联蛋白与内皮免疫球蛋白超家族(IgSF)蛋白质的动态相互作用决定。 我们已经鉴定了IgSF成员连接粘附分子-1(JAM-1)作为β2整联蛋白淋巴细胞功能相关抗原-1(LFA-1)的配体。 在静态和生理流动条件下,JAM-1促成T细胞和嗜中性粒细胞的LFA-1依赖性内皮细胞迁移,并且还引起LFA-1介导的趋化因子对由细胞因子共刺激的内皮触发的T细胞的停止, 从紧密的路口分发JAM-1。 表达JAM-1的转染子支持LFA-1介导的白细胞粘附,其需要JAM-1的膜近端Ig样结构域2。 因此,JAM-1是LFA-1的反受体,理想地位于引导和控制白细胞募集过程中的迁移。