EphrinB-mediated reverse signalling controls junctional integrity and pro-inflammatory differentiation of endothelial cells
The EphB/ephrinB receptor-ligand system is pivotal for the development of the embryonic vasculature and for angiogenesis in the adult organism. We observed that (i) the expression of ephrinB2 and ephrinB1 is up-regulated in capillaries during inflammation, that (ii) these ligands are localised on th...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
01. Dezember 2017
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| In: |
Thrombosis and haemostasis
Year: 2014, Volume: 112, Issue: 07, Pages: 151-163 |
| ISSN: | 2567-689X |
| DOI: | 10.1160/TH13-12-1034 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1160/TH13-12-1034 Verlag, lizenzpflichtig, Volltext: http://www.thieme-connect.de/DOI/DOI?10.1160/TH13-12-1034 
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| Author Notes: | Hui Liu, Kavi Devraj, Kerstin Möller, Stefan Liebner, Markus Hecker, Thomas Korff |
| Summary: | The EphB/ephrinB receptor-ligand system is pivotal for the development of the embryonic vasculature and for angiogenesis in the adult organism. We observed that (i) the expression of ephrinB2 and ephrinB1 is up-regulated in capillaries during inflammation, that (ii) these ligands are localised on the luminal endothelial surface, and that (iii) they interact with the ephrinB-receptor EphB2 on monocyte/macrophages. This study delineates the impact of ephrinB-mediated reverse signalling on the integrity and proinflammatory differentiation of the endothelium. To this end, <i>in vitro</i> analyses with human cultured endothelial cells reveal that knockdown of ephrinB2 or ephrinB1 impairs monocyte transmigration through the endothelium. While ephrinB2 but not ephrinB1 interacts with PECAM-1 (CD31) in this context, reverse signalling by ephrinB1 but not ephrinB2 elicits a c-Jun N-terminal kinase (JNK)-dependent up-regulation of E-selectin expression. Furthermore, treatment of endothelial cells with soluble EphB2 receptor bodies or EphB2-overexpressing mouse myeloma cells links ephrinB2 to PECAM-1 and induces its Src-dependent phosphorylation while diminishing Src homology phosphotyrosyl phosphatase-2 (SHP-2) activity and increasing endothelial cell permeability. We conclude that extravasation of EphB2 positive leukocyte populations is facilitated by lowering the integrity of endothelial cell junctions and enhancing the pro-inflammatory phenotype of the endothelium through activation of ephrinB ligands. |
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| Item Description: | Elektronische Reproduktion der Druckausgabe Gesehen am 21.08.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2567-689X |
| DOI: | 10.1160/TH13-12-1034 |