Homocysteine at pathophysiological concentrations enhances binding of dendritic cells to endothelial cells mediated by DC-SIGN

Elevated plasma homocysteine (Hey) is an independent risk factor for atherosclerosis, which is recognized as inflammatory and immune responses. The purpose of this study was to investigate the effect of Hey on the interaction between dendritic cells (DCs) and endothelial cells (ECs) by upregulating the expression of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in cultured DCs. The immunophenotype of Hcy-treated DCs was monitored by flow cytometry. Then, they were coincubated with cultured human umbilical vein endothelial cells, and adhesion of DCs to ECs, and migration of DCs through an endothelial monolayer growing on the insert of a transwell plate, were assessed using a confocal microscope and a multi-detection microplate reader. The expression of DC-SIGN on Hey-stimulated DCs was assessed by Western blot and immunofluorescence staining. The presence of Hey did not change the phenotype of immature and mature DCs. Hey promoted adhesion of DCs to ECs and migration in a concentration-dependent fashion. This effect was inhibited by an anti-DC-SIGN monoclonal antibody. The expression of DC-SIGN on DCs was significantly upregulated by Hey in a concentration-dependent manner. Taken together, our results show for the first time that Hey can potentiate the adhesion of DCs to ECs and migration by upregulating the expression of DC-SIGN on DCs, suggesting a novel role of Hey in the pathogenesis of human vascular disease. (c) 2007 Elsevier B.V. All rights reserved.