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F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling
- Source :
- Nature Communications, 7:10493. Nature Publishing Group, Nature Communications, Heemskerk, N, Schimmel, L, Oort, C, Van Rijssel, J, Yin, T, Ma, B, Van Unen, J, Pitter, B, Huveneers, S, Goedhart, J, Wu, Y, Montanez, E, Woodfin, A & Van Buul, J D 2016, ' F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling ', Nature Communications . https://doi.org/10.1038/ncomms10493, Nature Communications, Vol 7, Iss 1, Pp 1-17 (2016), Nature Communications. Nature Publishing Group, Nature communications, 7. Nature Publishing Group, Dipòsit Digital de la UB, Universidad de Barcelona
- Publication Year :
- 2016
-
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.<br />Endothelial cells can support leukocyte extravasation without causing vascular leakage, but the exact mechanism underlying this process has not been fully elucidated. Here the authors show that it is regulated through actomyosin-based endothelial pore confinement, which requires local endothelial RhoA activation.
- Subjects :
- 0301 basic medicine
Cellular signal transduction
RHOA
Endothelium
Neutrophils
Science
Intercellular Adhesion Molecule-1
General Physics and Astronomy
Vascular permeability
Epithelial cells
General Biochemistry, Genetics and Molecular Biology
Article
Capillary Permeability
03 medical and health sciences
Mice
Vascular endothelial growth factors
medicine
Human Umbilical Vein Endothelial Cells
Leukocytes
Animals
Humans
ROCK1
Cytoskeleton
Cells, Cultured
Cèl·lules epitelials
Multidisciplinary
biology
Factor de creixement de l'endoteli vascular
Transendothelial and Transepithelial Migration
Transducció de senyal cel·lular
General Chemistry
Actin cytoskeleton
Leukocyte extravasation
Metabolisme
Actins
Cell biology
Mice, Inbred C57BL
Actin Cytoskeleton
030104 developmental biology
medicine.anatomical_structure
Metabolism
biology.protein
Endothelium, Vascular
rhoA GTP-Binding Protein
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, 7:10493. Nature Publishing Group, Nature Communications, Heemskerk, N, Schimmel, L, Oort, C, Van Rijssel, J, Yin, T, Ma, B, Van Unen, J, Pitter, B, Huveneers, S, Goedhart, J, Wu, Y, Montanez, E, Woodfin, A & Van Buul, J D 2016, ' F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling ', Nature Communications . https://doi.org/10.1038/ncomms10493, Nature Communications, Vol 7, Iss 1, Pp 1-17 (2016), Nature Communications. Nature Publishing Group, Nature communications, 7. Nature Publishing Group, Dipòsit Digital de la UB, Universidad de Barcelona
- Accession number :
- edsair.doi.dedup.....4ebd1b0857135b28e7f9c2fcfd551749