A COMMON THEME IN ENDOTHELIAL ACTIVATION - INSIGHTS FROM THE STRUCTURAL-ANALYSIS OF THE GENES FOR E-SELECTIN AND VCAM-1

An important early step in the development of an inflammatory infiltrate is the induction of new endothelial cell surface proteins. Cytokine-induced expression of endothelial-leukocyte adhesion molecule-1 (E-selectin or ELAM-1) may mediate neutrophil adhesion to endothelium, whereas induced expression of vascular cell adhesion molecule (VCAM-1) may be important in the adhesion of mononuclear cells. Both the corresponding genes are transcriptionally regulated by the inflammatory cytokines. Structural analysis of the promoters of these genes reveals binding sites for the transcription factor nuclear factor kappaB (NF-kappaB). Activation of the pleiotropic mediator NF-kappaB in endothelial cells could coordinate the expression of numerous endothelial products that are important in endothelial activation, including some cell surface adhesion proteins, cytokines, growth factors, and components of the coagulation system.