EXPOSURE OF TUMOR-NECROSIS-FACTOR-ALPHA TO LUMINAL MEMBRANE OF BOVINE BRAIN CAPILLARY ENDOTHELIAL-CELLS COCULTURED WITH ASTROCYTES INDUCES A DELAYED INCREASE OF PERMEABILITY AND CYTOPLASMIC STRESS FIBER FORMATION OF ACTIN
EXPOSURE OF TUMOR-NECROSIS-FACTOR-ALPHA TO LUMINAL MEMBRANE OF BOVINE BRAIN CAPILLARY ENDOTHELIAL-CELLS COCULTURED WITH ASTROCYTES INDUCES A DELAYED INCREASE OF PERMEABILITY AND CYTOPLASMIC STRESS FIBER FORMATION OF ACTIN
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DOI：
10.1002/jnr.490410602
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发表时间：
1995-08-15
影响因子：
4.2
通讯作者：
TORPIER, G
中科院分区：
文献类型：
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作者：
DELI, MA;DESCAMPS, L;TORPIER, G
肿瘤坏死因子-α（TNF-α）是一种促炎细胞因子，长期以来一直被认为参与中枢神经系统感染和某些神经退行性疾病的发病机制。然而，在这些病理条件下，血脑屏障（BBB），血液循环和脑组织之间的活性界面的可能作用仍然未知。在我们的体外重建的BBB模型中，重组人TNF-α（浓度分别为50、250和500 U/ml）暴露于牛脑毛细血管内皮细胞（BBCEC）的管腔膜1小时，未显著改变蔗糖（m.w. 342 Da）或菊粉（m.w. 5 kDa），除了在2-4小时时最高剂量TNF-α的蔗糖渗透轻微降低（P < 0.05）。另一方面，在所有3种浓度的TNF-α（延迟相）激发1小时后16小时，两种标志物的BBCEC单层渗透性均诱导显著增加。这些变化的渗透性伴随着选择性重组的F-肌动蛋白丝成应力纤维，而波形蛋白的细胞内分布保持类似的控制。这些结果表明，BBCEC可以直接响应TNF-α的延迟增加的渗透性和重组的肌动蛋白丝。(C)1995 Wiley-Liss，Inc.
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has long been known to be involved in the pathogenesis of central nervous system infections and of certain neurodegenerative diseases. However, the possible role of the blood-brain barrier (BBB), the active interface between the blood circulation and brain tissue, remained unknown during these pathological conditions. In our in vitro reconstructed BBB model, 1-hr exposure of recombinant human TNF-alpha (in concentrations of 50, 250, and 500 U/ml, respectively) to the luminal membrane of bovine brain capillary endothelial cells (BBCEC) did not change significantly the transendothelial flux of either sucrose (m.w. 342 Da), or inulin (m.w. 5 kDa) up to 4 hr (early phase), except for a slight decrease (P < 0.05) in sucrose permeation at 2-4 hr with the highest dose of TNF-alpha. On the other hand, at 16 hr after the 1-hr challenge with TNF-alpha (delayed phase) at all 3 concentrations, significant increase was induced in the permeability of BBCEC monolayers for both markers. These changes of permeability were accompanied by a selective reorganization of F-actin filaments into stress fibers, while the intracellular distribution of vimentin remained similar to the control. These results suggest that BBCEC can respond directly to TNF-alpha by a delayed increase of permeability and reorganization of actin filaments. (C) 1995 Wiley-Liss, Inc.