Aho R, Jalkanen S, Kalimo H
Department of Pathology, University of Turku, Finland.
J Neuropathol Exp Neurol. 1994 May;53(3):295-302. doi: 10.1097/00005072-199405000-00011.
The cell adhesion molecule CD44 is expressed in the central nervous system, especially on glial cells in the white matter, the extracellular matrix of which also contains one of its ligands, hyaluronate. We investigated the role of CD44 and hyaluronate in the adhesion of human peripheral blood lymphocytes to myelinated areas of cerebellum by an in vitro binding assay. Hermes-1 epitope, which recognizes the hyaluronate binding site of CD44, and Hermes-3 epitope, involved in lymphocyte binding to mucosal high endothelial venules, were both immunohistochemically expressed in the white matter. No immunoreactivity was observed with mAb Var3.1, which sees variant forms of CD44 containing the exon v6 encoding region. The molecular weight analysis showed that CD44 of the white matter was identical to the major 90 kD form of CD44 present on lymphocytes. The binding of both T and B lymphocytes was significantly inhibited by pretreatment of both cells and sections with mAb Hermes-1 but not with Hermes-3. Digestion of the sections and/or lymphocytes with hyaluronidase also reduced lymphocyte binding. These findings implicate that CD44-hyaluronate mediates lymphocyte adhesion to the white matter and this interaction may be involved in the pathogenesis of inflammations and lymphomas of the central nervous system.
细胞粘附分子CD44在中枢神经系统中表达，尤其在白质中的神经胶质细胞上表达，其细胞外基质中还含有其配体之一透明质酸。我们通过体外结合试验研究了CD44和透明质酸在人外周血淋巴细胞与小脑有髓鞘区域粘附中的作用。识别CD44透明质酸结合位点的Hermes-1表位和参与淋巴细胞与粘膜高内皮微静脉结合的Hermes-3表位在白质中均通过免疫组织化学表达。用识别含编码区外显子v6的CD44变异形式的单克隆抗体Var3.1未观察到免疫反应性。分子量分析表明，白质中的CD44与淋巴细胞上存在的主要90kD形式的CD44相同。用单克隆抗体Hermes-1预处理细胞和切片可显著抑制T淋巴细胞和B淋巴细胞的结合，而用Hermes-3预处理则无此作用。用透明质酸酶消化切片和/或淋巴细胞也可减少淋巴细胞的结合。这些发现表明，CD44-透明质酸介导淋巴细胞与白质的粘附，这种相互作用可能参与中枢神经系统炎症和淋巴瘤的发病机制。
