THE STUDY FOR ADHESION SYSTEMS OF LYMPHOCYTES AND CANCER CELLS TO LYMPHATIC ENDOTHELIUM

在癌细胞与淋巴管的粘附系统中，我们发现desmoplakin是淋巴内皮的特异性标记物（Ebata等人，2001年1a， b）。我们现在正在研究desmoplakin是否有助于口腔鳞状细胞癌与淋巴内皮的粘附。在淋巴细胞与淋巴管的粘附系统中，我们用人小肠检测了cys-cys （C-C）趋化因子配体21 （CCL21）在次级淋巴组织中的表达，以及toll样受体（TLR）2和TLR4的表达。这些表达在收集淋巴管中未被清楚检测到，但在中央乳管和固有层粘膜中表达CCL21的淋巴毛细血管中观察到TLRs 2和4的表达，而在血管中未被清楚观察到CCL21和TLRs的表达（Kuroshima et al., 2004a）。tlr感知病原体相关分子模式（PAMPs）并诱导细胞因子的产生。我们的研究结果表明，CCL21和TLRs 2和4的表达主要在小肠微循环的外周淋巴内皮中被诱导，并且淋巴内皮可能通过TLRs的表达促进淋巴细胞进入次级淋巴组织，PAMPs的参与导致趋化因子的诱导。在未发炎的人牙龈粘膜结缔组织乳头的所有淋巴毛细血管中均检测到CCL21的表达，而有两种类型的收集淋巴管表达CCL21和不表达CCL21。在炎症牙龈中，淋巴管未检测到CCL21的表达。没有血管表达CCL21。这些结果可能表明CCL21的表达主要在未发炎的牙龈粘膜微循环的外周淋巴内皮中被诱导，并且在发炎的条件下，CCL21的减少发生在淋巴内皮中（Kuroshima et al., 2004b）。

On the adhesion systems of cancer cells to lymphatic vessels we showed that desmoplakin is a specific marker for lymphatic endothelium (Ebata et al., 2001a, b). We are now investigating whether desmoplakin aids the adhesion of oral squamous cell carcinoma to lymphatic endothelium. On the adhesion systems of lymphocytes to lymphatic vessels we examined the expressions of cys-cys (C-C) chemokine ligand 21 (CCL21) expressing in secondary lymphoid tissues, and of toll-like receptor (TLR)2 and TLR4, using human small intestine. These expressions were not clearly detected on collecting lymphatic vessels but the expression of TLRs 2 and 4 was observed on the central lacteals and lymphatic capillaries expressing CCL21 in the lamina propria mucosae whereas the expression of CCL21 and TLRs was not clearly observed in blood vessels (Kuroshima et al., 2004a). The TLRs sense pathogen-associated molecular patterns (PAMPs) and induce cytokine production. Our results suggests that the expression of CCL21, and TLRs 2 and 4 is predominantly induced in the peripheral lymphatic endothelium of the small intestinal microcirculation, and that the lymphatic endothelium may contribute to allow lymphocytes to home into secondary lymphoid tissue through the expression of TLRs, PAMPs engagements of which result in the chemokine induction. In uninflamed human gingiva the CCL21 expression was detected on all lymphatic capillaries of the mucosal connective tissue papillae while there were two types of collecting lymphatic vessels expressing CCL21 or not. In inflamed gingiva no CCL21 expression was detected on lymphatic vessels. No blood vessels expressed CCL21. These results may suggest that the CCL21 expression is predominantly induced in the peripheral lymphatic endothelium of the uninflamed mucosal microcirculation of gingiva, and that under inflamed conditions a reduction of CCL21 occurs in lymphatic endothelium (Kuroshima et al., 2004b).