Interaction of endothelial cells and neutrophils in vitro: kinetics of thrombomodulin, intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1): implications for the relevance as serological disease activity markers in vasculitides.

Abstract

Recently markers of endothelial cell activation or injury gained increasing interest as serological parameters of disease activation in vasculitides. Among these, soluble serum thrombomodulin, ICAM-1, VCAM-1 and E-selectin are of particular interest. However, only thrombomodulin showed the expected close correlation. The objective of this study was to investigate in vitro the kinetics of these endothelial cell receptors after interaction of unstimulated or cytokine-activated polymorphonuclear neutrophils (PMN) and endothelial cells in order to find evidence explaining these different clinical findings. Over the time period of up to 48 h of incubation the kinetics of thrombomodulin, ICAM-1, E-selectin, and VCAM-1 levels in the supernatant of endothelial cells in co-culture with neutrophils were determined in vitro by ELISA under basal and partially cytokine-activated (tumour necrosis factor-alpha) conditions. Increased levels of ICAM-1, E-selectin and VCAM-1 were already found due to cytokine activation of endothelial cells alone. This increase was augmented after coincubation with neutrophils. In contrast, a significant increase of thrombomodulin in the supernatant was only found due to cell injury after cell-cell interaction of cytokine-activated endothelial cells with neutrophils. In conclusion, this in vitro model of the kinetics of soluble endothelial cell receptors after cell-cell interaction of cytokine-activated PMN and endothelial cells underlines the advantage of thrombomodulin in contrast to the adhesion molecules as a marker of endothelial damage. Therefore, soluble thrombomodulin seems to be a promising, valuable serological disease activity marker in vasculitides.