Regulation by Cytokines and Lipopolysaccharide of E-selectin Expression by Human Brain Microvessel Endothelial Cells in Primary Culture

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Abstract
E-selectin is an adhesion molecule expressed on endothelial cells after treatment with inflammatory agents in vitro and in inflammatory diseases in vivo. Interactions between leukocytes and endothelial cells are mediated partly through this adhesion molecule. In this study, the kinetic expression of E-selectin by human cerebral endothelium was studied under standard conditions and following treatment of primary cultures with bacterial lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). Surface expression of E-selectin was detected by immunocytochemistry, ELISA and immunoelectron microscopy. Untreated human cerebral endothelial cells constitutively expressed low levels of E-selectin. Treatment with LPS, TNF-α and IL-1β increased the mean level of E-selectin expression per cell and the percentage of cells expressing E-selectin, in a time- and concentration-dependent manner. E-selectin expression was maximal by 4 h post-stimulation and returned to unstimulated levels by 48 h. LPS and TNF-α were most effective followed by IL-1β, while the IFN-γ had no effect on E-selectin expression. Immunoelectron microscopy demonstrated that E-selectin was preferentially expressed on the apical surface of unstimulated and TNF-α treated cells. Cytokine stimulation induced a several-fold increase of E-selectin expression on the apical and to a lesser extent on the basal cell surface. Modulation of E-selectin expression on cerebral endothelium by inflammatory cytokines suggests a potentially important role of this adhesion molecule in the recruitment of leukocytes in central nervous system (CNS) inflammation.

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