Receptor-mediated transcytosis of transferrin through blood-brain barrier endothelial cells
Receptor-mediated transcytosis of transferrin through blood-brain barrier endothelial cells
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DOI：
10.1152/ajpheart.1996.270.4.h1149
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发表时间：
1996-04-01
影响因子：
4.8
通讯作者：
Cecchelli, R
中科院分区：
文献类型：
--
作者：
Descamps, L;Dehouck, MP;Cecchelli, R
由牛脑毛细血管内皮细胞 (BBCEC) 和星形胶质细胞共培养组成的血脑屏障细胞培养模型已用于检查铁转运到大脑的机制。结合实验表明，BBCEC 每个细胞表达 35,000 个高亲和力（50% 受体饱和度时的浓度 = 11.3 +/- 2.1 nM）转铁蛋白 (Tf) 受体。与载脂蛋白转铁蛋白 (apoTf) 相比，我们观察到全转铁蛋白 (holoTf) 在 BBCEC 上的特异性转运。这种运输在低温下被完全抑制。此外，抗 Tf 受体抗体 (OX-26) 竞争性抑制 BBCEC 对 HoloTf 的摄取。脉冲追踪实验表明，只有 10% 的 Tf 被再循环到细胞的管腔侧，而大部分 Tf 被转胞吞到管腔侧；双标记实验清楚地表明铁可以穿过与 Tf 结合的 BBCEC。没有观察到 Tf 的内皮内降解，这表明通过 BBCEC 的内皮内途径绕过了溶酶体区室。这些结果清楚地表明，铁-Tf 复合物通过受体介导的途径转胞吞穿过脑毛细血管内皮细胞，而没有任何降解。
A cell culture model of the blood-brain barrier consisting of a coculture of bovine brain capillary endothelial cells (BBCECs) and astrocytes has been used to examine the mechanism of iron transport to the brain. Binding experiments showed that BBCECs express 35,000 high-affinity (concn at 50% receptor saturation = 11.3 +/- 2.1 nM) transferrin (Tf) receptors per cell. In contrast to apo-transferrin (apoTf), we observed a specific transport of holo-transferrin (holoTf) across BBCECs. This transport was inhibited completly at low temperature. Moreover, the anti-Tf receptor antibody (OX-26) competitively inhibited holoTf uptake by BBCECs. Pulse-chase experiments demonstrated that only 10% of Tf was recycled to the luminal side of the cells, whereas the majority of Tf was transcytosed to the abluminal side; double-labeling experiments clearly demonstrated that iron crosses BBCECs bound to Tf. No intraendothelial degradation of Tf was observed, suggesting that the intraendothelial pathway through BBCECs bypasses the lysosomal compartment. These results clearly show that the iron-Tf complex is transcytosed across brain capillary endothelial cells by a receptor-mediated pathway without any degradation.