Format

Send to

Choose Destination
J Cell Sci. 2014 Oct 15;127(Pt 20):4470-82. doi: 10.1242/jcs.154708. Epub 2014 Aug 8.

Actin-binding proteins differentially regulate endothelial cell stiffness, ICAM-1 function and neutrophil transmigration.

Author information

1
Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center and Swammerdam Institute of Life Sciences, University of Amsterdam, 1066 CX Amsterdam, The Netherlands a.schaefer@sanquin.nl p.hordijk@sanquin.nl.
2
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen 6525 GA, The Netherlands.
3
Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
4
Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center and Swammerdam Institute of Life Sciences, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
5
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Erratum in

  • J Cell Sci. 2014 Nov 15;127(22):4985.
  • J Cell Sci. 2014 Oct 15;127(Pt 20):doi/10.1242/jcs.164814.

Abstract

Chronic vascular inflammation is driven by interactions between activated leukocytes and the endothelium. Leukocyte β2-integrins bind to endothelial intercellular adhesion molecule 1 (ICAM-1), which allows leukocyte spreading, crawling and transendothelial migration. Leukocytes scan the vascular endothelium for permissive sites to transmigrate, which suggests that there is apical membrane heterogeneity within the endothelium. However, the molecular basis for this heterogeneity is unknown. Leukocyte adhesion induces ICAM-1 clustering, which promotes its association to the actin-binding proteins filamin B, α-actinin-4 and cortactin. We show that these endothelial proteins differentially control adhesion, spreading and transmigration of neutrophils. Loss of filamin B, α-actinin-4 and cortactin revealed adaptor-specific effects on a nuclear-to-peripheral gradient of endothelial cell stiffness. By contrast, increasing endothelial cell stiffness stimulates ICAM-1 function. We identify endothelial α-actinin-4 as a key regulator of endothelial cell stiffness and of ICAM-1-mediated neutrophil transmigration. Finally, we found that the endothelial lining of human and murine atherosclerotic plaques shows elevated levels of α-actinin-4. These results identify endothelial cell stiffness as an important regulator of endothelial surface heterogeneity and of ICAM-1 function, which in turn controls the adhesion and transmigration of neutrophils.

KEYWORDS:

Adhesion; Endothelium; Inflammation; Transmigration

PMID:
25107367
DOI:
10.1242/jcs.154708
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center