Endothelial cell expression of monocyte chemotactic protein-1, tissue factor, and thrombomodulin on hydrophilic plasma polymers

Endothelial cells (EC) from human aortas, microvessels, and pulmonary arter ies were examined for their expression and activity of monocyte chemotactic protein-1 (MCP-1), tissue factor, and thrombomodulin in response to tumor necrosis factor-alpha (TNF alpha) on the hydrophilic plasma polymers gamma- butyrolactone (GBL) and N-vinyl-2-pyrrolidone (NVP), along with a fibronect in (FN) control. RNAs isolated from EC grown on these substrates were subje cted to reverse ttanscription-polymerase chain reaction (RT-PCR) and dot-bl ot analysis. EC expression of MCP-1 and tissue factor was very low in the a bsence of TNFa but high for constitutively expressed thrombomodulin. TNF al pha induced EC expression and activity of MCP-1 and tissue factor and suppr essed that of thrombomodulin on all substrates. Greater differences were se en with regard to cell origin, but little difference was seen among substra tes. Basal secretion of MCP-1 was very low in aortic and pulmonary artery E C and even Less in microvascular EC. TNF alpha increased MCP-1 secretion si gnificantly in aortic and pulmonary artery EC but to a lesser extent in mic rovascular EC. In contrast, tissue factor expression was greater in pulmona ry artery EC compared to microvascular and aortic EC. Basal expression of t hrombomodulin was largely comparable for all three cell types grown on diff erent surfaces,but TNF alpha suppressed thrombomodulin to different extents depending on the origin of the EC; The activity of tissue factor and throm bomodulin and the secretion of MCP-1 by EC were largely correlated with the expression of these genes. We conclude that EC origin may be an important determinant of cellular function on hydrophilic plasma polymer substrates. However, the differences in cellular function due to variations in substrat e surface hydrophilicity could have been masked by the extracellular:matrix remodeling that presumably occurred during EC growth to confluence. (C) 20 00 John Wiley & Sons, Inc.