诱导血脑屏障特性需要内皮细胞与星形胶质细胞的相互作用以及转化生长因子β。

Endothelial cell-astrocyte interactions and TGF beta are required for induction of blood-neural barrier properties.

作者信息

Garcia Claudia M, Darland Diane C, Massingham Lauren J, D'Amore Patricia A

机构信息

Biological and Biomedical Sciences Graduate Program, Harvard Medical School, Boston, MA, USA.

出版信息

Brain Res Dev Brain Res. 2004 Aug 18;152(1):25-38. doi: 10.1016/j.devbrainres.2004.05.008.

DOI:10.1016/j.devbrainres.2004.05.008

PMID:15283992

Abstract

We sought to establish a blood-neural barrier (BNB) model of astrocyte contact with endothelial cells (EC) to test the hypothesis that transforming growth factor beta (TGF beta) promotes an EC barrier-phenotype. Astrocyte-EC contact induced BNB properties in EC. Transendothelial resistance was augmented by direct contact between astrocytes-EC, but not by astrocyte-conditioned medium or astrocyte-EC coculture conditioned medium. Coculture of EC and astrocytes led to significant increase in endothelial occludin levels and junctional localization. EC gamma-glutamyl-transferase (GGT) activity was increased by direct contact with astrocytes, by conditioned medium from cocultures or by TGF beta1. Coculture inhibited EC proliferation with no effect on astrocyte proliferation. A neutralizing antibody to TGF beta decreased GGT activity in cocultures and increased cell number. Whereas total TGF beta was not significantly altered by coculture, activated TGF beta increased in astrocyte-EC cocultures. In summary, astrocyte-EC contact induces BNB characteristics in EC and locally activated TGF beta is responsible for part of the induction.

摘要

我们试图建立一种星形胶质细胞与内皮细胞（EC）接触的血神经屏障（BNB）模型，以验证转化生长因子β（TGFβ）促进EC屏障表型这一假说。星形胶质细胞与EC的接触诱导了EC的BNB特性。星形胶质细胞与EC的直接接触增强了跨内皮电阻，但星形胶质细胞条件培养基或星形胶质细胞与EC共培养条件培养基则无此作用。EC与星形胶质细胞共培养导致内皮闭合蛋白水平显著增加并定位于连接处。与星形胶质细胞直接接触、共培养条件培养基或TGFβ1均可增加ECγ-谷氨酰转移酶（GGT）活性。共培养抑制了EC增殖，对星形胶质细胞增殖无影响。抗TGFβ中和抗体降低了共培养中的GGT活性并增加了细胞数量。虽然共培养未显著改变总TGFβ水平，但星形胶质细胞与EC共培养中活化的TGFβ增加。总之，星形胶质细胞与EC的接触诱导了EC的BNB特性，局部活化的TGFβ是诱导作用的部分原因。