science20130118-3

来自奥地利科学与技术研究院的研究人员在小鼠皮肤中发现免疫细胞——树突细胞会沿着趋化因子CCL21固定的化学浓度梯度,定向迁移到淋巴管中。

-2013年1月18日《科学》

中文翻译


【题目】免疫树突细胞定向迁移机制

【译文】免疫细胞沿着趋化因子的化学浓度梯度定向迁移,这被认为是胚胎发育、癌症播散和免疫反应的关键。然而,这一观点仍然缺乏直接的活体实验证实。本研究检测到小鼠皮肤的趋化因子CCL21的内源性化学浓度梯度,发现它能引导树突细胞移向淋巴管。定量磁共振成像技术揭示淋巴管内皮细胞内聚集大量的CCL21,同时外淋巴间质内CCL21的化学浓度梯度急剧降低。这些化学浓度梯度与树突细胞的迁移模式相匹配,它引导树突细胞从长达90微米的距离外定向迁移到淋巴管中。组织间质中的CCL21可被硫酸乙酰肝素固定,实验性消除或扰乱CCL21的内源性化学浓度梯度会消除这种定向迁移。这些发现确定了趋化性这一概念的功能,即引导树突细胞沿着组织中固定的化学浓度梯度定向迁移。

英文原稿


[Title]: Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients

[Authors]: Michele Weber, Robert Hauschild, Jan Schwarz, Christine Moussion, Ingrid de Vries, Daniel F. Legler, Sanjiv A. Luther, Tobias Bollenbach, and Michael Sixt

[Abstract]: Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.  

原文地址

http://www.sciencemag.org/content/339/6117/328.short

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