Dendritic cells lower the permeability of endothelial monolayers

Abstract

The permeability of cultured endothelial monolayers is higher than the permeability of endothelium in vivo. Co-culture with astrocytes can induce a tight, blood-brainbarrier phenotype in aortic endothelium in vitro. We hypothesized that dendritic cells, which reside in the intima of noncerebral 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 (S1P), which mediates the barrier-tightening effect of platelets, but inhibitors of S1P 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. © 2012 Biomedical Engineering Society.