IST Austria (Institute of Science and Technology Austria), Klosterneuburg, Austria.
Science. 2013 Jan 18;339(6117):328-32. doi: 10.1126/science.1228456.
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.
趋化因子浓度梯度引导细胞的方向被认为对胚胎发育、癌症扩散和免疫反应至关重要。然而，这一概念在体内仍然缺乏直接的实验证实。在这里，我们在小鼠皮肤中鉴定出趋化因子 CCL21 的内源性梯度，并表明它们引导树突状细胞向淋巴管移动。定量成像显示 CCL21 在内皮细胞内有储存库，在淋巴管周围间质中呈陡峭下降的梯度。这些梯度与树突状细胞的迁移模式相匹配，它们从长达 90 微米的距离定向接近血管。间质中的 CCL21 固定在硫酸乙酰肝素上，其实验去定位或淹没内源性梯度会破坏定向迁移。这些发现从功能上确立了组织中沿着固定梯度的趋化性（定向迁移）的概念。
