Molecular characterization of lymphatic endothelial cells

Molecular characterization of lymphatic endothelial cells
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DOI:
10.1073/pnas.242401399
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发表时间:
2002-12-10
影响因子:
11.1
通讯作者:
Skobe, M
Skobe, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Podgrabinska, S;Braun, P;Skobe, M

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淋巴微血管系统是唯一适合于连续清除间质液和蛋白质,是白细胞和肿瘤细胞的重要入口点。淋巴管的特殊功能表明淋巴管和血管内皮的分子组成不同。然而,这两种细胞类型的差异程度仍不清楚,迄今为止,很少有真正特异于淋巴管内皮细胞的分子被鉴定出来。我们已经分离出初级淋巴和血液微血管内皮细胞从人类皮肤的淋巴标记物LYVE-1的免疫选择,并证明这两个细胞系表达不同的血管标记物和不同的生长因子和细胞外基质的反应。基因表达谱的比较微阵列分析揭示了一些独特的分子特性,区分淋巴和血液血管内皮。淋巴管内皮的分子特征似乎反映了毛细淋巴管的特征性功能和结构特征。将差异表达的基因分类为功能组揭示了特别高水平的涉及蛋白质分选和运输的基因,表明淋巴管内皮在分子的摄取和运输中比以前预期的更活跃的作用。大量的基因选择性表达的淋巴管内皮细胞的鉴定应促进发现迄今未知的淋巴管标记物,并提供了基础的分子机制的分析占毛细淋巴管的特征功能。
The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins and is an important entry point for leukocytes and tumor cells. Specialized functions of lymphatics suggest differences in the molecular composition of the lymphatic and blood vascular endothelium. However, the extent to which the two cell types differ is still unclear, and few molecules that are truly specific to lymphatic endothelial cells have been identified to date. We have isolated primary lymphatic and blood microvascular endothelial cells from human skin by immunoselection with the lymphatic marker LYVE-1 and demonstrate that the two cell lineages express distinct sets of vascular markers and respond differently to growth factors and extracellular matrix. Comparative microarray analysis of gene-expression profiles revealed a number of unique molecular properties that distinguish lymphatic and blood vascular endothelium. The molecular profile of lymphatic endothelium seems to reflect characteristic functional and structural features of the lymphatic capillaries. Classification of the differentially expressed genes into functional groups revealed particularly high levels of genes implicated in protein sorting and trafficking, indicating a more active role of lymphatic endothelium in uptake and transport of molecules than previously anticipated. The identification of a large number of genes selectively expressed by lymphatic endothelium should facilitate the discovery of hitherto unknown lymphatic vessel markers and provide a basis for the analysis of the molecular mechanisms accounting for the characteristic functions of lymphatic capillaries.