Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier
Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier
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DOI：
10.1074/jbc.274.11.7011
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发表时间：
1999-03-12
影响因子：
4.8
通讯作者：
Pierce, A
中科院分区：
文献类型：
--
作者：
Fillebeen, C;Descamps, L;Pierce, A
乳铁蛋白（Lf）是一种铁结合蛋白，参与宿主对感染和严重炎症的防御;它在神经退行性疾病期间在大脑中积累。在确定Lf在脑组织中的功能之前，我们研究了它的起源，并在这里证明它穿过血脑屏障。使用血脑屏障的体外模型来检查Lf转运到脑的机制。我们报告说，分化的牛脑毛细血管内皮细胞表现出特定的高（Kd = 37.5 nM; n = 90，000/细胞）和低（Kd = 2 μ M; n = 900，000网站/细胞）的亲和力结合位点。只有后者存在于未分化的细胞。表面结合的Lf仅被分化的细胞群体内化，从而得出Lf受体在细胞分化过程中获得的结论。然后通过受体介导的过程发生特定的单向运输，没有明显的内皮内降解。我们进一步报告，铁可以通过牛脑毛细血管内皮细胞作为一个复杂的Lf，最后，我们表明，低密度脂蛋白受体相关蛋白可能参与了这一过程，因为它的特异性拮抗剂，受体相关蛋白，抑制70%的Lf运输。
Lactoferrin (Lf) is an iron-binding protein involved in host defense against infection and severe inflammation; it accumulates in the brain during neurodegenerative disorders. Before determining Lf function in brain tissue, we investigated its origin and demonstrate here that it crosses the blood-brain barrier. An in vitro model of the blood-brain barrier was used to examine the mechanism of Lf transport to the brain. We report that differentiated bovine brain capillary endothelial cells exhibited specific high (K-d = 37.5 nM; n = 90,000/cell) and low (K-d = 2 mu M; n = 900,000 sites/cell) affinity binding sites. Only the latter were present on nondifferentiated cells. The surface-bound Lf was internalized only by the differentiated cell population leading to the conclusion that Lf receptors were acquired during cell differentiation. A specific unidirectional transport then occurred via a receptor-mediated process with no apparent intraendothelial degradation. We further report that iron may cross the bovine brain capillary endothelial cells as a complex with Lf, Finally, we show that the low density lipoprotein receptor-related protein might be involved in this process because its specific antagonist, the receptor-associated protein, inhibits 70% of Lf transport.