Homocysteine at pathophysiological concentrations enhances binding of dendritic cells to endothelial cells mediated by DC-SIGN.
Elevated plasma homocysteine (Hcy) 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 Hcy 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 Hcy-stimulated DCs was assessed by Western blot and immunofluorescence staining. The presence of Hcy did not change the phenotype of immature and mature DCs. Hcy 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 Hcy in a concentration-dependent manner. Taken together, our results show for the first time that Hcy can potentiate the adhesion of DCs to ECs and migration by upregulating the expression of DC-SIGN on DCs, suggesting a novel role of Hcy in the pathogenesis of human vascular disease.
Li
Shan
S
Department of Cardiology, First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310003, People's Republic of China.
Zhu
Wei-guo
WG
Yan
Hui
H
Fan
Fang-yan
FY
Sun
Pei-yu
PY
Zhu
Jian-hua
JH
D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006710:Homocysteine / Q000502:physiology* / Q000633:toxicity; D006801:Humans; D037181:Lectins, C-Type / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D006710:Homocysteine; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin