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EPH receptor B2 stimulates human monocyte adhesion and migration independently of its EphrinB ligands
Author(s) -
Vreeken Dianne,
Bruikman Caroline Suzanne,
Cox Stefan Martinus Leonardus,
Zhang Huayu,
Lalai Reshma,
Koudijs Angela,
Zonneveld Anton Jan,
Hovingh Gerard Kornelis,
Gils Janine Maria
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.2a0320-283rr
Subject(s) - ephrin , erythropoietin producing hepatocellular (eph) receptor , monocyte , biology , microbiology and biotechnology , stimulation , receptor , adhesion , immunology , signal transduction , endocrinology , chemistry , biochemistry , organic chemistry , receptor tyrosine kinase
The molecular basis of atherosclerosis is not fully understood and mice studies have shown that Ephrins and EPH receptors play a role in the atherosclerotic process. We set out to assess the role for monocytic EPHB2 and its Ephrin ligands in human atherosclerosis and show a role for EPHB2 in monocyte functions independently of its EphrinB ligands. Immunohistochemical staining of human aortic sections at different stages of atherosclerosis showed that EPHB2 and its ligand EphrinB are expressed in atherosclerotic plaques and that expression proportionally increases with plaque severity. Functionally, stimulation with EPHB2 did not affect endothelial barrier function, nor did stimulation with EphrinB1 or EphrinB2 affect monocyte‐endothelial interactions. In contrast, reduced expression of EPHB2 in monocytes resulted in decreased monocyte adhesion to endothelial cells and a decrease in monocyte transmigration, mediated by an altered morphology and a decreased ability to phosphorylate FAK. Our results suggest that EPHB2 expression in monocytes results in monocyte accumulation by virtue of an increase of transendothelial migration, which can subsequently contribute to atherosclerotic plaque progression.