Please use this identifier to cite or link to this item:
Title: F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local rhoA signaling in vivo
Author: Heemskerk, Niels
Schimmel, Lilian
Oort, Chantal
Yin, Taofei
Ma, Bin
Van Unen, Jakobus
Pitter, Bettina
Huveneers, Stephan
Goedhart, Joachim
Wu, Yi
Montañez, Eloi
Woodfin, Abigail
Van Buul, Jaap D.
Van Rijssel, Jos
Keywords: Metabolisme
Transducció de senyal cel·lular
Factor de creixement de l'endoteli vascular
Cèl·lules epitelials
Cellular signal transduction
Vascular endothelial growth factors
Epithelial cells
Issue Date: 27-Jan-2016
Publisher: Nature Publishing Group
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.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2016, vol. 7, p. 10493
Related resource:
ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

Files in This Item:
File Description SizeFormat 
697741.pdf3.8 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons