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静脉注射免疫球蛋白 (IVIg) 与低密度脂蛋白受体相关蛋白 1 之间的相互作用:是否在血脑屏障的胞转作用中有一定作用?

Interaction between intravenous immunoglobulin (IVIg) and the low-density lipoprotein receptor-related protein 1: a role for transcytosis across the blood brain barrier?

机构信息

Department of Research and Development, Héma-Québec, Québec, Canada.

出版信息

J Neuroimmunol. 2012 Oct 15;251(1-2):39-44. doi: 10.1016/j.jneuroim.2012.06.009. Epub 2012 Jul 15.

DOI:10.1016/j.jneuroim.2012.06.009
PMID:22796178
Abstract

Intravenous immunoglobulin (IVIg) is a therapeutic preparation of plasma-derived human IgG and is increasingly used for the treatment of several neurological inflammatory disorders. However, it is not clear whether the IgG molecules contained in IVIg can actually cross the BBB in treated patients. We recently showed that LRP1, an endocytic receptor involved in transcytosis of several proteins across the BBB was able to interact with IVIg. In the present study, we show that LRP1 is involved in IVIg internalization inside living cells. Our data also suggest that following internalization, IVIg is recycled to the cell surface, raising the possibility that LRP1 can mediate IVIg transcytosis across the BBB. Finally, we show that IVIg-LRP1 interaction leads to LRP1 tyrosine phosphorylation.

摘要

静脉注射免疫球蛋白(IVIg)是一种源自血浆的人 IgG 治疗制剂,越来越多地用于治疗几种神经炎症性疾病。然而,目前尚不清楚 IVIg 中所含的 IgG 分子是否能真正穿过治疗患者的 BBB。我们最近发现,LRP1 是一种参与几种蛋白穿过 BBB 的胞吞作用的内吞受体,能够与 IVIg 相互作用。在本研究中,我们发现 LRP1 参与了 IVIg 在活细胞内的内化。我们的数据还表明,内化后,IVIg 被循环到细胞表面,这增加了 LRP1 介导 IVIg 穿过 BBB 的可能性。最后,我们发现 IVIg-LRP1 相互作用导致 LRP1 酪氨酸磷酸化。

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