LIPOPOLYSACCHARIDE-INDUCED E-SELECTIN EXPRESSION REQUIRES CONTINUOUS PRESENCE OF LPS AND IS INHIBITED BY BACTERICIDAL PERMEABILITY-INCREASING PROTEIN/

Endothelial cells stimulated by LPS express E-selectin, which plays an important role in mediating neutrophil adhesion during inflammation. E-selectin is induced within 1-2 h, peaks at 4-6 h, and gradually retu rns to basal level by 24 h. rBPI(21), a recombinant N-terminal fragmen t of human bactericidal/permeability-increasing protein (BPI), inhibit ed LPS-induced E-selectin expression when added at the same time as, a nd up to 6 h after, LPS. Delayed administration of rBPI(21) also affec ted LPS-mediated activation of the nuclear factor, NF-kappa B. Two to 4 h following LPS addition to endothelial cells, when NF-kappa B was a lready activated, addition of rBPI(21) resulted in marked reduction of NF-kappa B detectable at 4 or 6 h. These results indicate that endoth elial activation requires continuous presence of LPS, and rBPI(21) act s to reverse LPS-mediated endothelial activation by interrupting the o n-going LPS signal.