Elucidation and Control of Adhesion Cascade in Lymphocyte Homing

前人和我们的工作表明，多种黏附分子参与淋巴结内淋巴细胞与HEV(高内皮微静脉)的相互作用，它们介导黏附级联，只有淋巴细胞才能在淋巴结内循环。在本研究中，我们寻找了L-选择素的配体，并研究了L-选择素在这一现象中的作用。主要研究结果如下：1.利用重组可溶性L-选择素，从大鼠淋巴结裂解液中获得180 kDa的分子。该分子与以往从分子大小判断的L-选择素配体如GlyCAM-1和CD34明显不同。纯化了180 kDa分子，并测定了其N-末端氨基酸序列。分析表明，该分子与主要表达于巨噬细胞的人甘露糖受体高度同源。用抗大鼠甘露糖受体的多克隆抗血清证实，甘露糖受体在巨噬细胞中表达，而在HEV中不表达。因此，180 kDa的分子可能参与了淋巴细胞与HEV之间的粘附级联反应。另外，我们还检测了L-选择素是否能传递信号，发现该分子确实能传递由外而内的信号，尽管细胞内只有13个氨基酸。这表明L-选择素存在一个具有信号转导能力的关联分子(S)。

Previous work by others and ourselves indicate that a variety of adhesion molecules are involved in the interaction between lymphocytes and HEV (high endothelial venules) in lymph nodes and that they mediate an adhesion cascade so that only lymphocytes can recirculate through lymph nodes. In this study, we searched for ligands for L-selectin and investigated the role of L-selectin in this phenomenon. Our results are summarized as follows ;1. By the use of recombinant soluble L-selectin, 180kDa molecule was obtained from rat lymph node lysates. This molecule is apparently different from previously identified L-selectin ligands such as GlyCAM-1 and CD34as judged by the molecular size.2. The 180kDa molecule was purified and its N-termnal amino acid sequence was determined.3. The analysis indicated that this molecule is hightly homologous to human mannose receptor which is mainly expressed in macrophages.4. By the use of polyclonal antiserum against rat mannose receptor, it was revealed that mannose receptor is expressed in medullary macrophages but not in HEV.Therefore, it is unlilely that the 180kDa molecule is involved in the adhesion cascade occurring between lymphocytes and HEV.Separately, we examined if L-selectin can transduce signal, and found out that this molecule can indeed transmit outside-in signal, although it has only 13 amino acid recidues intracellularly. This indicates that L-selectin has an associated molecule (s) with signal transducing ability.