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Elucidation and Control of Adhesion Cascade in Lymphocyte Homing

淋巴细胞归巢中粘附级联的阐明和控制

基本信息

批准号：
05454214
负责人：
MIYASAKA Masayuki
金额：
$ 4.1万
依托单位：
Osaka University (1994-1995)Tokyo Metropolitan Organization for Medical Research (1993)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

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.

其他人和我们以前的工作表明，各种粘附分子参与淋巴结中淋巴细胞和HEV（高内皮微静脉）之间的相互作用，并且它们介导粘附级联反应，使得只有淋巴细胞可以通过淋巴结再循环。在这项研究中，我们寻找L-选择素的配体，并研究L-选择素在这种现象中的作用。我们的研究结果总结如下：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。从分子大小上看，该分子与以前鉴定的L-选择素配体如GlyCAM-1和CD 34明显不同.纯化了180 kDa的分子，并测定了其N端氨基酸序列.分析表明，该分子与主要在巨噬细胞中表达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，发现甘露糖受体在骨髓巨噬细胞中表达，而在戊型肝炎病毒中不表达。因此，180 kDa的分子参与淋巴细胞与戊型肝炎病毒之间的粘附级联反应是不可能的。另外，我们检测了L-选择素是否可以阻断信号，发现该分子确实可以传递由外向内的信号，尽管它只有13个氨基酸在细胞内重复。这表明L-选择素具有信号转导能力的相关分子。