Picker L J, Nakache M, Butcher E C
Department of Pathology, Stanford University School of Medicine, California.
J Cell Biol. 1989 Aug;109(2):927-37. doi: 10.1083/jcb.109.2.927.
A 90-kD lymphocyte surface glycoprotein, defined by monoclonal antibodies of the Hermes series, is involved in lymphocyte recognition of high endothelial venules (HEV). Lymphocyte gp90Hermes binds in a saturable, reversible fashion to the mucosal vascular addressin (MAd), a tissue-specific endothelial cell adhesion molecule for lymphocytes. We and others have recently shown that the Hermes antigen is identical to or includes CD44 (In[Lu]-related p80), human Pgp-1, and extracellular matrix receptor III-molecules reportedly expressed on diverse cell types. Here, we examine the relationship between lymphoid and nonlymphoid Hermes antigens using serologic, biochemical, and, most importantly, functional assays. Consistent with studies using mAbs to CD44 or Pgp-1, mAbs against five different epitopes on lymphocyte gp90Hermes reacted with a wide variety of nonhematolymphoid cells in diverse normal human tissues, including many types of epithelium, mesenchymal elements such as fibroblasts and smooth muscle, and a subset of glia in the central nervous system. To ask whether these non-lymphoid molecules might also be functionally homologous to lymphocyte homing receptors, we assessed their ability to interact with purified MAd using fluorescence energy transfer techniques. The Hermes antigen isolated from both glial cells and fibroblasts--which express a predominant 90-kD form similar in relative molecular mass, isoelectric point, and protease sensitivity to lymphocyte gp90Hermes--was able to bind purified MAd. In contrast, a 140-160-kD form of the Hermes antigen isolated from squamous epithelial cells lacked this capability. Like lymphocyte binding to mucosal HEV, the interaction between glial gp90Hermes and MAd is inhibited by mAb Hermes-3, but not Hermes-1, suggesting that similar molecular domains are involved in the two binding events. The observation that the Hermes/CD44 molecules derived from several nonlymphoid cell types display binding domains homologous to those of lymphocyte homing receptors suggests that these glycoproteins represent a novel type of cell adhesion/recognition molecule (H-CAM) potentially mediating cell-cell or cell-matrix interactions in multiple tissues.
一种由Hermes系列单克隆抗体所界定的90-kD淋巴细胞表面糖蛋白，参与淋巴细胞对高内皮微静脉（HEV）的识别。淋巴细胞gp90Hermes以可饱和、可逆的方式与黏膜血管地址素（MAd）结合，MAd是一种淋巴细胞的组织特异性内皮细胞黏附分子。我和其他人最近表明，Hermes抗原与CD44（In[Lu]相关的p80）、人Pgp-1以及据报道在多种细胞类型上表达的细胞外基质受体III分子相同或包含这些分子。在这里，我们使用血清学、生物化学以及最重要的功能测定来研究淋巴样和非淋巴样Hermes抗原之间的关系。与使用抗CD44或Pgp-1单克隆抗体的研究一致，针对淋巴细胞gp90Hermes上五个不同表位的单克隆抗体与多种正常人体组织中的多种非血液淋巴样细胞发生反应，包括许多类型的上皮细胞、间充质成分如成纤维细胞和平滑肌，以及中枢神经系统中的一部分神经胶质细胞。为了探究这些非淋巴样分子是否也在功能上与淋巴细胞归巢受体同源，我们使用荧光能量转移技术评估了它们与纯化的MAd相互作用的能力。从神经胶质细胞和成纤维细胞中分离出的Hermes抗原——它们表达一种在相对分子质量、等电点和蛋白酶敏感性方面与淋巴细胞gp90Hermes相似的主要90-kD形式——能够结合纯化的MAd。相比之下，从鳞状上皮细胞中分离出的140 - 160-kD形式的Hermes抗原缺乏这种能力。与淋巴细胞与黏膜HEV的结合一样，神经胶质gp90Hermes与MAd之间的相互作用被单克隆抗体Hermes-3抑制，但不被Hermes-1抑制，这表明相似的分子结构域参与了这两种结合事件。源自几种非淋巴样细胞类型的Hermes/CD44分子显示出与淋巴细胞归巢受体同源的结合结构域，这一观察结果表明这些糖蛋白代表了一种新型的细胞黏附/识别分子（H-CAM），可能在多种组织中介导细胞间或细胞与基质的相互作用。
