Dendritic Cells Lower the Permeability of Endothelial Monolayers

The permeability of cultured endothelial monolayers is higher than the permeability of endothelium in vivo . Co-culture with astrocytes can induce a tight, blood-brain-barrier phenotype in aortic endothelium in vitro . We hypothesised that dendritic cells, which reside in the intima of non-cerebral arteries and have features in common with astrocytes, may also reduce the permeability of cultured aortic endothelium. The permeability of porcine aortic endothelial monolayers was reduced by non-contact co-culture with dendritic cells (but not with the peripheral blood monocytes from which they were derived) and by dendritic cell conditioned medium, indicating a soluble mediator. The reduction in permeability was similar to that obtained by co-culture with astrocytes; however, dendritic cells did not up-regulate P-glycoprotein and there was no synergy with the effect of chronic shear stress on permeability, contrary to observations with astrocytes. Endothelial permeability was reduced by sphingosine-1-phosphate, which mediates the barrier-tightening effect of platelets, but inhibitors of sphingosine-1-phosphate receptors did not block the effect of dendritic cells. Rates of endothelial mitosis and apoptosis were also unaffected by co-culture. Hence dendritic cells reduce permeability by different mechanisms from those mediating barrier-tightening effects of astrocytes and platelets, although factors mediating the permeability-lowering effects of chronic shear stress may be involved. We speculate that dendritic cells influence endothelial permeability in vivo .