Upregulation of the Low Density Lipoprotein Receptor at the Blood-Brain Barrier: Intercommunications between Brain Capillary Endothelial Cells and Astrocytes

1987 ◽  
Vol 84 (1) ◽  
pp. 465-473
Author(s):  
Bénédicte Dehouck ◽  
Marie-Pierre Dehouck ◽  
Jean-Charles Fruchart ◽  
Roméo Cecchelli

In contrast to the endothelial cells in large vessels where LDL receptors are downregulated, brain capillary endothelial cells in vivo express an LDL receptor. Using a cell culture model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells and astrocytes, we observed that the capacity of endothelial cells to bind LDL is enhanced threefold when cocultured with astrocytes. We next investigated the ability of astrocytes to modulate endothelial cell LDL receptor expression. We have shown that the lipid requirement of astrocytes increases the expression of endothelial cell LDL receptors. Experiments with dialysis membranes of different pore size showed that this effect is mediated by a soluble factor(s) with relative molecular mass somewhere between 3,500 and 14,000. Substituting astrocytes with smooth muscle cells or brain endothelium with endothelium from the aorta or the adrenal cortex did not enhance the luminal LDL receptor expression on endothelial cells, demonstrating the specificity of the interactions. This factor(s) is exclusively secreted by astrocytes cocultured with brain capillary endothelial cells, but it also upregulates the LDL receptor on other cell types. This study confirms the notion that the final fine tuning of cell differentiation is under local control.

1994 ◽  
Vol 126 (2) ◽  
pp. 465-473 ◽  
Author(s):  
B Dehouck ◽  
M P Dehouck ◽  
J C Fruchart ◽  
R Cecchelli

In contrast to the endothelial cells in large vessels where LDL receptors are downregulated, brain capillary endothelial cells in vivo express an LDL receptor. Using a cell culture model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells and astrocytes, we observed that the capacity of endothelial cells to bind LDL is enhanced threefold when cocultured with astrocytes. We next investigated the ability of astrocytes to modulate endothelial cell LDL receptor expression. We have shown that the lipid requirement of astrocytes increases the expression of endothelial cell LDL receptors. Experiments with dialysis membranes of different pore size showed that this effect is mediated by a soluble factor(s) with relative molecular mass somewhere between 3,500 and 14,000. Substituting astrocytes with smooth muscle cells or brain endothelium with endothelium from the aorta or the adrenal cortex did not enhance the luminal LDL receptor expression on endothelial cells, demonstrating the specificity of the interactions. This factor(s) is exclusively secreted by astrocytes cocultured with brain capillary endothelial cells, but it also upregulates the LDL receptor on other cell types. This study confirms the notion that the final fine tuning of cell differentiation is under local control.


1996 ◽  
Vol 270 (4) ◽  
pp. H1149-H1158 ◽  
Author(s):  
L. Descamps ◽  
M. P. Dehouck ◽  
G. Torpier ◽  
R. Cecchelli

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) transferin (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 completely 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.


PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48428 ◽  
Author(s):  
Barbara Deracinois ◽  
Sophie Duban-Deweer ◽  
Gwënaël Pottiez ◽  
Roméo Cecchelli ◽  
Yannis Karamanos ◽  
...  

2009 ◽  
Vol 65 ◽  
pp. S150
Author(s):  
Yoshifumi Sonobe ◽  
Hideyuki Takeuchi ◽  
Kunio Kataoka ◽  
Hua Li ◽  
Shijie Jin ◽  
...  

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