SELECTIVE-INHIBITION OF E-SELECTIN, ICAM-1, AND VCAM IN ENDOTHELIAL-CELLS

Endothelial cells, as they normally exist in the vasculature as quiesc ent cells, perform several functions. In an inflammatory response, end othelial cells are activated to up-regulate a number of genes, includi ng E-selectin (ELAM-1), VCAM-1, ICAM-1, interleukin (IL)-1, IL-8 and p lasminogen activator inhibitor-1 (PAI-1). Very little is known about f actors that regulate the activation process. We describe here that a h eat-stable protein, normally present in the alpha-globulin fraction of serum, inhibits induced expression of E-selectin, ICAM-1, and VCAM-1 in vitro and also impedes the accumulation of mRNA for these molecules . Inhibition of E-selectin, the only gene tested in this respect, is a t the level of transcription. At the same time, the alpha-globulins do not, under the same conditions, repress mRNA accumulation for IL-1, I L-8, or PAI-1. The effect of the inhibitor does not relate to constrai nts on function of nuclear-factor chi B, the induced activity of which is not interfered with at the early time points at which the suppress ion of these three genes is seen.