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

淋巴细胞和癌细胞对淋巴内皮粘附系统的研究

基本信息

批准号：
12470379
负责人：
SAWA Yoshihiko
金额：
$ 9.92万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

项目摘要

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).

关于癌细胞与淋巴管的粘附系统，我们表明桥粒斑蛋白是淋巴管内皮的特异性标志物（Ebata等人，2001 a，B）。我们现在正在研究桥粒斑蛋白是否有助于口腔鳞状细胞癌与淋巴管内皮的粘附。在淋巴细胞与淋巴管的粘附系统上，我们使用人小肠检测了在次级淋巴组织中表达的cys-cys（C-C）趋化因子配体21（CCL 21）的表达，以及Toll样受体（TLR）2和TLR 4的表达。这些表达在集合淋巴管上未被清楚地检测到，但在粘膜固有层中表达CCL 21的中央乳糜管和毛细淋巴管上观察到TLR 2和4的表达，而在血管中未清楚地观察到CCL 21和TLR的表达（Kuroshima et al.，2004年a）。TLR感知病原体相关分子模式（PAMP）并诱导细胞因子产生。我们的研究结果表明，CCL 21，TLRs 2和4的表达主要是诱导在小肠微循环的外周淋巴管内皮细胞，淋巴管内皮细胞可能有助于允许淋巴细胞回家到次级淋巴组织通过表达TLRs，PAMPs的参与导致趋化因子的诱导。在未发炎的人牙龈中，在粘膜结缔组织乳头的所有毛细淋巴管上检测到CCL 21的表达，而有两种类型的集合淋巴管表达或不表达CCL 21。在发炎的牙龈中，在淋巴管上没有检测到CCL 21表达。无血管表达CCL 21。这些结果可能表明，CCL 21的表达主要在牙龈未发炎的粘膜微循环的外周淋巴内皮中诱导，并且在发炎条件下，淋巴内皮中发生CCL 21的减少（Kuroshima等人，2004年b）。