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

关于癌细胞与淋巴管的黏附系统，我们发现桥粒蛋白是淋巴管内皮细胞的特异性标记物(Ebata等人，2001a，b)。我们现在正在研究桥粒蛋白是否有助于口腔鳞状细胞癌与淋巴管内皮细胞的黏附。在淋巴细胞与淋巴管的黏附系统上，我们用人小肠观察了次级淋巴组织中Cys-Cys(C-C)趋化因子配体21(CCL21)的表达，以及Toll样受体(TLR)2和TLR4的表达。这些表达在收集的淋巴管上未见明显表达，但在固有层表达CCL21的中央乳管和毛细淋巴管上可观察到TLR2和TLR4的表达，而在血管中未见CCL21和TLRs的表达(Kuroshima等，2004a)。TLRs可感知病原体相关分子模式(PAMPs)并诱导细胞因子的产生。我们的结果表明，CCL21和TLR2和TLR4的表达主要是在小肠微循环的外周淋巴管内皮细胞中诱导的，淋巴管内皮细胞可能通过TLRs的表达，PAMPs的参与导致趋化因子的诱导，帮助淋巴细胞归巢到次级淋巴组织中。在未发炎的人牙龈组织中，CCL21表达于粘膜结缔组织乳头的所有毛细淋巴管中，但有两种类型的集合性淋巴管表达CCL21。炎症牙周组织中淋巴管未见CCL21表达。无血管表达CCL21。这些结果可能表明CCL21的表达主要是在未发炎的牙龈粘膜微循环的外周淋巴管内皮细胞中诱导的，而在炎症条件下，CCL21的表达在淋巴管内皮细胞中发生减少(Kuroshima等人，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).