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Neutrophil adhesion under flow conditions induces zyxin nuclear translocation in endothelial cells
Author(s) -
Bowley Erin Nicole,
Patel Kamala,
Colarusso Pina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1071.5
Subject(s) - focal adhesion , chromosomal translocation , microbiology and biotechnology , downregulation and upregulation , mechanotransduction , chemistry , biology , signal transduction , gene , biochemistry
High shear stress causes zyxin translocation from focal adhesions (FA) to stress fibers. We previously showed that leukocyte adhesion to stimulated endothelial cells (EC) activated mechanosensitive signaling pathways in ECs at low shear stress, which in turn modulated leukocyte transmigration. In this study, we examined the remodeling of the FA protein zyxin following neutrophil (PMN) adhesion under shear stress and determined if downregulating this protein altered PMN transmigration. Zyxin localized to FAs and stress fibers under static conditions. Buffer perfusion across TNFα‐stimulated ECs did not change zyxin localization at lower shear stresses, but resulted in modest nuclear translocation of zyxin at a shear stress of 4 dyne/cm 2 . In contrast, PMN recruitment to TNFα‐stimulated ECs resulted in a loss of zyxin from FAs and translocation of zyxin to the nucleus at shear stresses as low as 1 dyne/cm 2 . Translocation specifically occured in ECs with adherent PMNs and did not occur in ECs distant from regions containing adherent PMNs. Perfusion of fixed PMNs, which roll but to do not adhere or transmigrate, did not induce changes in zyxin localization. Finally, zyxin downregulation in ECs attenuated PMN transmigration. These data suggest that PMN trafficking across stimulated ECs leads to focal adhesion remodeling and that EC zyxin nuclear translocation during this process may play a potential role in gene transcription. Funding: Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research.