Nandi Animesh, Estess Pila, Siegelman Mark
Laboratory of Molecular Pathology, Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Immunity. 2004 Apr;20(4):455-65. doi: 10.1016/s1074-7613(04)00077-9.
CD44 on activated T cells can initiate contact and mediate rolling on hyaluronan on endothelial cells. We have shown that the integrin VLA-4 is used preferentially over LFA-1 in conjunction with this rolling interaction for firm adhesion. Here, we show by coimmunoprecipitation and transfection studies that CD44 associates with VLA-4 but not LFA-1 on the plasma membrane of immune cells. Absence of the cytoplasmic portion of CD44 abrogates this coassociation and attendant firm adhesion. Moreover, in an in vivo model of lymphocyte homing, cells expressing only the truncated form of CD44 together with VLA-4 fail to traffic to an inflamed site, thereby defining a discrete biological role for the cytoplasmic domain. These studies demonstrate a molecular mechanism whereby coanchoring within a single bimolecular complex between a primary and secondary adhesion molecule regulates a cell's ability to firmly adhere, providing a fundamental alteration to the paradigm of leukocyte extravasation.
活化T细胞上的CD44可启动与内皮细胞上透明质酸的接触并介导滚动。我们已经表明，整合素VLA-4在这种滚动相互作用中比LFA-1更优先用于牢固黏附。在此，我们通过免疫共沉淀和转染研究表明，在免疫细胞质膜上，CD44与VLA-4而非LFA-1相关联。CD44细胞质部分的缺失消除了这种共关联及随之而来的牢固黏附。此外，在淋巴细胞归巢的体内模型中，仅表达截短形式的CD44与VLA-4的细胞无法迁移至炎症部位，从而确定了细胞质结构域的一个独特生物学作用。这些研究证明了一种分子机制，即一级和二级黏附分子之间在单个双分子复合物中的共同锚定调节细胞牢固黏附的能力，这为白细胞外渗范式带来了根本性改变。
