Comparison of basal and TNFa-induced ICAM-1 and VCAM-1 expression in various human endothelial cell types and smooth muscle cells

Adhesion molecules on endothelial cells (EC) mediate leukocyte extravasation. Previous studies suggest heterogeneity in the biological responses of EC derived from different vascular beds. In this study, we used a fluorescent ELISA to compare basal and tumor necrosis factor a- (TNFa) induction of intracellular adhesion rnolecule-1 (ICAM) and vascular cell adhesion molecule-1 (VCAM) in cultured human EC derived from aortae (HAEC), vena cavae (HVCEC) and microvascularure (HMVEC), and also in human vena cava smooth muscle cells (HVCSM). Both time- (0-24 hr) and dose-dependency (0-100 ng/ml) of TNFainduction were explored. In time-dependent studies, maximal TNFa-induced ICAM and VCAM levels were observed after 8 hr in all 4 cell types. Basal ICAM in HAEC was 2-3 fold higher than in HMVEC or HVCEC. Despite different basal levels, all three EC types exhibited similar maximal increases of ICAM ( 3-fold t), with TNFa-stimulation. In HVCSM, basal ICAM expression was undetectable, however, TNFa-treatment resulted in maximal ICAM levels that were 40-50% of EC maximal levels. In contrast, basal VCAM levels were similar in all EC types, as were TNFa-induced levels (6-fold t). Basal VCAM levels in HVCSM were the same as in EC, but were less responsive to TNFa-stimulation (2-fold ). Variant basal ICAM in EC might explain observed diversity in leukocyte/EC interactions in various vascular beds. Currently, we are comparing leukocyte binding to these diverse vascular cells.