Nakache M, Berg E L, Streeter P R, Butcher E C
Department of Pathology, Stanford University, California 94305.
Nature. 1989 Jan 12;337(6203):179-81. doi: 10.1038/337179a0.
Tissue position-dependent or address-dependent expression of cell adhesion molecules has been proposed to play a part in cellular positioning in a variety of systems, for example during neural development, the metastasis of neoplasms, and the tissue-specific homing of lymphocytes. The extravasation of blood-borne lymphocytes is regulated by interactions with the endothelium of specialised venules, such as the high endothelial venules (HEV) in organized lymph nodes and mucosal lymphoid tissues. At least three separate lymphocyte-HEV recognition systems have been described, one mediating tissue-selective lymphocyte interactions with HEV in peripheral lymph nodes, another in mucosal lymphoid organs, and a third in inflamed synovium. We have previously identified a tissue-specific 'vascular addressin' in the mouse which is selectively expressed by venules mediating lymphocyte-homing into mucosal tissues. To determine whether this addressin is a specific adhesion molecule for lymphocytes, we have isolated it by monoclonal antibody-affinity chromatography and inserted it into supported phospholipid planar membranes. Lymphocytes bind to membranes containing the addressin, but not to phospholipid bilayers or to control glycophorin-reconstituted membranes. Only those lymphocytes and lymphoma cell lines capable of binding to mucosal HEV adhere well to the isolated addressin; peripheral lymph node HEV-specific or HEV-non-binding cell lines do not bind. Binding is blocked by anti-addressin antibody MECA-367. We conclude that the mucosal vascular addressin is a tissue-specific endothelial cell-adhesion molecule for lymphocytes, and suggest that it could regulate lymphocyte traffic into mucosal tissues by mediating attachment of blood-borne cells to endothelium.
细胞黏附分子的组织位置依赖性或地址依赖性表达被认为在多种系统中的细胞定位过程中发挥作用，例如在神经发育、肿瘤转移以及淋巴细胞的组织特异性归巢过程中。血源性淋巴细胞的渗出是由与特殊小静脉内皮的相互作用所调节的，比如在有组织的淋巴结和黏膜淋巴组织中的高内皮小静脉（HEV）。至少已经描述了三种不同的淋巴细胞-HEV识别系统，一种介导外周淋巴结中淋巴细胞与HEV的组织选择性相互作用，另一种在黏膜淋巴器官中，第三种在炎症滑膜中。我们之前在小鼠中鉴定出一种组织特异性的“血管地址素”，它由介导淋巴细胞归巢至黏膜组织的小静脉选择性表达。为了确定这种地址素是否是淋巴细胞的特异性黏附分子，我们通过单克隆抗体亲和层析将其分离，并将其插入支持的磷脂平面膜中。淋巴细胞与含有该地址素的膜结合，但不与磷脂双层或对照糖蛋白重构膜结合。只有那些能够与黏膜HEV结合的淋巴细胞和淋巴瘤细胞系能很好地黏附于分离出的地址素；外周淋巴结HEV特异性或不与HEV结合的细胞系则不结合。结合被抗地址素抗体MECA-367阻断。我们得出结论，黏膜血管地址素是淋巴细胞的组织特异性内皮细胞黏附分子，并表明它可能通过介导血源性细胞与内皮的附着来调节淋巴细胞进入黏膜组织的运输。
