Elucidation and Control of Adhesion Cascade in Lymphocyte Homing

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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.