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Ephrin-A1/EphA4-mediated adhesion of monocytes to endothelial cells.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2013 Oct; Vol. 1833 (10), pp. 2201-11. Date of Electronic Publication: 2013 May 23. - Publication Year :
- 2013
-
Abstract
- The Eph receptors represent the largest family of receptor tyrosine kinases. Both Eph receptors and their ephrin ligands are cell-surface proteins, and they typically mediate cell-to-cell communication by interacting at sites of intercellular contact. The major aim of the present study was to investigate the involvement of EphA4-ephrin-A1 interaction in monocyte adhesion to endothelial cells, as this process is a crucial step during the initiation and progression of the atherosclerotic plaque. Immunohistochemical analysis of human atherosclerotic plaques revealed expression of EphA4 receptor and ephrin-A1 ligand in major cell types within the plaque. Short-time stimulation of endothelial cells with the soluble ligand ephrin-A1 leads to a fourfold increase in adhesion of human monocytes to endothelial cells. In addition, ephrin-A1 further increases monocyte adhesion to already inflamed endothelial cells. EphrinA1 mediates its effect on monocyte adhesion via the activated receptor EphA4. This ephrinA1/EphA4 induced process involves the activation of the Rho signaling pathway and does not require active transcription. Rho activation downstream of EphA4 leads to increased polymerization of actin filaments in endothelial cells. This process was shown to be crucial for the proadhesive effect of ephrin-A1. The results of the present study show that ephrin-A1-induced EphA4 forward signaling promotes monocyte adhesion to endothelial cells via activation of RhoA and subsequent stress-fiber formation by a non-transcriptional mechanism.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Atherosclerosis genetics
Atherosclerosis pathology
Blotting, Western
Cell Proliferation
Cells, Cultured
Endothelium, Vascular cytology
Ephrin-A1 antagonists & inhibitors
Ephrin-A1 genetics
Ephrin-A4 antagonists & inhibitors
Ephrin-A4 genetics
Flow Cytometry
Humans
Immunoenzyme Techniques
Immunoprecipitation
Lipoproteins, LDL genetics
Lipoproteins, LDL metabolism
Macrophages cytology
Macrophages metabolism
Monocytes cytology
RNA, Messenger genetics
RNA, Small Interfering genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
rhoA GTP-Binding Protein genetics
rhoA GTP-Binding Protein metabolism
Atherosclerosis metabolism
Cell Adhesion
Endothelium, Vascular metabolism
Ephrin-A1 metabolism
Ephrin-A4 metabolism
Monocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1833
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 23707953
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2013.05.017