title: TNF-α-mediated adhesion of monocytes to endothelial cells-The role of ephrinA1.
abstract: The ligand ephrin A1 is more often discussed to play a role in the development of the atherosclerotic plaque and in this context especially in the monocyte adhesion to endothelial cells. As tumor necrosis factor-α (TNF-α) is known to induce monocyte adhesion to endothelium and ephrin A1 expression, the present study focuses on the involvement of ephrin A1 in TNF-α-mediated monocyte adhesion. The analysis of different members of the Eph/ephrin system in TNF-α-treated human umbilical vein endothelial cells (HUVEC) revealed that especially ephrinA1 was found to be highly regulated by TNF-α compared to other members of the Eph family. This effect is also present in arterial endothelial cells from the umbilical artery and from the coronary artery. This regulation is dependent on NFκB-activation as shown by the expression of a constitutive-active IκB-mutant. By using siRNA-mediated silencing and adenoviral overexpression of ephrinA1 in HUVEC, the involvement of ephrinA1 in the TNF-α triggered monocyte adhesion to endothelial cells could be demonstrated. In addition, these results could be verified by quantitative adhesion measurement using atomic force microscopy-based single-cell force spectroscopy and under flow conditions. Furthermore, this effect is mediated via the EphA4 receptor. EphrinA1 does not influence the mRNA or protein expression of the adhesion receptors VCAM-1 and ICAM-1 in endothelial cells. However, the surface presentation of these adhesion receptors is modulated in an ephrinA1-dependent manner. In conclusion, these data demonstrate that ephrinA1 plays an important role in the TNF-α-mediated adhesion of monocytes to endothelial cells, which might be of great importance in the context of atherosclerosis.
authors.affiliation: Internal Medicine and Cardiology, Heart Center Dresden, TU Dresden, Germany. Electronic address: georg.ende1@mailbox.tu-dresden.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Ende
authors.affiliation: Internal Medicine and Cardiology, Heart Center Dresden, TU Dresden, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Poitz
authors.affiliation: Internal Medicine and Cardiology, Heart Center Dresden, TU Dresden, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Wiedemann
authors.affiliation: Internal Medicine and Cardiology, Heart Center Dresden, TU Dresden, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Augstein
authors.affiliation: Institute for Biofunctional Polymer Materials Dresden, Leibniz Institute of Polymer Research, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Friedrichs
authors.affiliation: Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Germany.
authors.forename: Sindy
authors.initials: S
authors.lastname: Giebe
authors.affiliation: Internal Medicine, Department of Cardiology, Angiology and Pneumology, Magdeburg University, Magdeburg, Germany.
authors.forename: Sönke
authors.initials: S
authors.lastname: Weinert
authors.affiliation: Institute for Biofunctional Polymer Materials Dresden, Leibniz Institute of Polymer Research, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
authors.affiliation: Internal Medicine and Cardiology, Heart Center Dresden, TU Dresden, Germany.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
authors.affiliation: Internal Medicine and Cardiology, Heart Center Dresden, TU Dresden, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jellinghaus
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D004730:Endothelium, Vascular / Q000473:pathology; D036382:Ephrin-A1 / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D036382:Ephrin-A1; D008070:Lipopolysaccharides; D016328:NF-kappa B; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
keywords: Adhesion; Atherosclerosis; Endothelial cells; Monocytes; TNF-α