Estradiol reduces basal and cytokine induced monocyte adhesion to endothelial cells

Objective: To investigate the effect of 17beta-estradiol (E-2) on binding of monocytes to human aortic endothelial cells (HAECs) with or without cytokine induction. Methods: Confluent monolayers of HAECs were incubated with or without E-2 for 48 h prior to the monocyte adhesion assay. In studies with cytokines, 1 ng/ml tumor necrosis factor-alpha (TNF-alpha), 20 U/ml interleukin-1beta (IL-1beta) or both were added to the culture medium for the final 24 or 4 h. For the measurement of monocyte adhesion, H-3-thymidine labeled human THP-1 monocytes (4 x 10(5) cells per well) were added to the confluent monolayer of HAECs and incubated at 37 degreesC for 90 min. The unbound THP-1 cells were removed by gentle washing, and bound cells were digested with NaOH and quantified by measuring radioactivity. Results: When HAECs were pretreated for 48 h with E-2 the basal adhesion of THP-1 cells was reduced by an average of 28%. Estrogen significantly reduced cytokine-induced adhesion by 30-35`o when the cytokines were added for 4 h. When the cytokine treatment was prolonged to 24 h, pretreatment of HAECs with E-2 had no effect on THP-1 cell adhesion. Conclusions: E-2 reduces basal and short-term cytokine induced monocyte binding to HAECs. Since monocyte adhesion to vascular endothelial cells is one of the initial steps in the pathogenesis of atherosclerosis, E-2 may mediate vascular protection by reducing monocyte-endothelial cell binding in the early stages of atherogenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.