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 infiltra te is the induction of new endothelial cell surface proteins. Cytokine -induced expression of endothelial-leukocyte adhesion molecule-1 (E-se lectin or ELAM-1) may mediate neutrophil adhesion to endothelium, wher eas induced expression of vascular cell adhesion molecule (VCAM-1) may be important in the adhesion of mononuclear cells. Both the correspon ding genes are transcriptionally regulated by the inflammatory cytokin es. Structural analysis of the promoters of these genes reveals bindin g sites for the transcription factor nuclear factor kappaB (NF-kappaB) . Activation of the pleiotropic mediator NF-kappaB in endothelial cell s could coordinate the expression of numerous endothelial products tha t are important in endothelial activation, including some cell surface adhesion proteins, cytokines, growth factors, and components of the c oagulation system.