Astrocyte-mediated induction of alkaline phosphatase activity in human umbilical cord vein endothelium: an in vitro model.

The blood-brain barrier, localized in the endothelium of the cerebral capillaries, is characterized by the existence of tight junctions, a low mitochondrial density, a low number of vesicles and a high activity of certain enzymes like alkaline phosphatase and gamma-glutamyl transpeptidase. Astroglial cells secrete a product that induces brain microvessel endothelial cells to differentiate into endothelial cells with blood-brain barrier properties. If rat astrocytes were grown together with human umbilical cord vein endothelial cells in a co-culture system in which there is no cellular contact between both cell types, alkaline phosphatase activity was induced in the endothelial cells after three days of co-culturing. If the endothelial cells were cultured in astrocyte conditioned medium, alkaline phosphatase activity was also induced, and preliminary results showed that formation of tight junctions occurred after five days. These observations support the hypothesis that astrocytes induce the differentiation of non-blood-brain barrier endothelial cells into endothelial cells with blood-brain barrier properties, in this study based on alkaline phosphatase-activity induction and induction of tight junction formation. These inductive processes are produced by a soluble factor released by the astrocytes.