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

In contrast to the endothelial cells in large vessels where low densit y lipoprotein receptors are down regulated 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 e ndothelial cells and astrocytes, we observed that the capacity of endo thelial cells to bind LDL is enhanced 3 fold when cocultured with astr ocytes. We next investigated the ability of astrocytes to modulate end othelial cell LDL receptor expression. We have shown that the lipid re quirement of astrocytes increases the expression of endothelial cell L DL receptors. Experiments with dialysis membranes of different pore si ze showed that this effect is mediated by a soluble factor(s) with a m olecular mass somewhere between 3,500 and 14,000. Substituting astrocy tes with smooth muscle cells or brain endothelium with endothelium fro m the aorta or the adrenal cortex did not enhance the luminal LDL rece ptor expression on endothelial cells, demonstrating the specificity of the interactions. This study demonstrates that a crosstalk takes plac e between brain capillary endothelial cells and astrocytes. (C)1997, M edikal Press.