UP-REGULATION OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR AT THE BLOOD-BRAIN-BARRIER - INTERCOMMUNICATIONS BETWEEN BRAIN CAPILLARY ENDOTHELIAL-CELLS AND ASTROCYTES

In contrast to the endothelial cells in large vessels where LDL recept ors are downregulated, brain capillary endothelial cells in vivo expre ss an LDL receptor. Using a cell culture model of the blood-brain barr ier consisting of a coculture of brain capillary endothelial cells and astrocytes, we observed that the capacity of endothelial cells to bin d LDL is enhanced threefold when cocultured with astrocytes. We next i nvestigated the ability of astrocytes to modulate endothelial cell LDL receptor expression. We have shown that the lipid requirement of astr ocytes increases the expression of endothelial cell LDL receptors. Exp eriments with dialysis membranes of different pore size showed that th is effect is mediated by a soluble factor(s) with relative molecular m ass somewhere between 3,500 and 14,000. Substituting astrocytes with s mooth muscle cells or brain endothelium with endothelium from the aort a or the adrenal cortex did not enhance the luminal LDL receptor expre ssion on endothelial cells, demonstrating the specificity of the inter actions. This factor(s) is exclusively secreted by astrocytes cocultur ed 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.