F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling

Niels Heemskerk, Lilian Schimmel, Chantal Oort, Jos van Rijssel, Taofei Yin, Bin Ma, Jakobus van Unen, Bettina Pitter, Stephan Huveneers, Joachim Goedhart, Yi Wu, Eloi Montanez, Abigail Woodfin and Jaap D. van Buul ()
Additional contact information
Niels Heemskerk: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam
Lilian Schimmel: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam
Chantal Oort: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam
Jos van Rijssel: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam
Taofei Yin: Genetics and Developmental Biology, Center for Cell Analyses and Modelling, University of Connecticut Health Centre
Bin Ma: Experimental Medicine and Pharmacology, Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London
Jakobus van Unen: Molecular Cytology, Swammerdam Institute for Life Sciences, University of Amsterdam
Bettina Pitter: Walter-Brendel-Center of Experimental Medicine Ludwig-Maximilians University
Stephan Huveneers: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam
Joachim Goedhart: Molecular Cytology, Swammerdam Institute for Life Sciences, University of Amsterdam
Yi Wu: Genetics and Developmental Biology, Center for Cell Analyses and Modelling, University of Connecticut Health Centre
Eloi Montanez: Walter-Brendel-Center of Experimental Medicine Ludwig-Maximilians University
Abigail Woodfin: Experimental Medicine and Pharmacology, Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London
Jaap D. van Buul: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract During immune surveillance and inflammation, leukocytes exit the vasculature through transient openings in the endothelium without causing plasma leakage. However, the exact mechanisms behind this intriguing phenomenon are still unknown. Here we report that maintenance of endothelial barrier integrity during leukocyte diapedesis requires local endothelial RhoA cycling. Endothelial RhoA depletion in vitro or Rho inhibition in vivo provokes neutrophil-induced vascular leakage that manifests during the physical movement of neutrophils through the endothelial layer. Local RhoA activation initiates the formation of contractile F-actin structures that surround emigrating neutrophils. These structures that surround neutrophil-induced endothelial pores prevent plasma leakage through actomyosin-based pore confinement. Mechanistically, we found that the initiation of RhoA activity involves ICAM-1 and the Rho GEFs Ect2 and LARG. In addition, regulation of actomyosin-based endothelial pore confinement involves ROCK2b, but not ROCK1. Thus, endothelial cells assemble RhoA-controlled contractile F-actin structures around endothelial pores that prevent vascular leakage during leukocyte extravasation.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms10493 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10493

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10493

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().