Effects of tumor necrosis factor on receptor-mediated endocytosis and barrier functions of bovine brain capillary endothelial cell monolayers.

Tumor necrosis factor alpha (TNF-alpha) plays a crucial role in the pathogenesis of the central nervous system infections. In an in vitro reconstructed blood-brain barrier model, a significant dysregulation of receptor mediated endocytosis of low density lipoproteins (LDL) and transferrin (Tf) is demonstrated at delayed phase of direct TNF-alpha activation. Concomitant with the increase in LDL uptake, we demonstrate a decrease of Tf-receptor mediated endocytosis. The potential role of TNF action in the differential or opposite routing of macromolecules is also characterized by a stimulation of their transcytosis. These findings may provide a new insight into the inflammatory effect of TNF-alpha on brain capillary endothelial cells.