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2016-01-27

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cc-by (c) Heemskerk, Niels et al., 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/155800

F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local rhoA signaling in vivo

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https://doi.org/10.1038/ncomms10493

Resum

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.

Matèries

Metabolisme, Transducció de senyal cel·lular, Factor de creixement de l'endoteli vascular, Cèl·lules epitelials

Matèries (anglès)

Metabolism, Cellular signal transduction, Vascular endothelial growth factors, Epithelial cells

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Col·leccions

Articles publicats en revistes (Ciències Fisiològiques)

Citació

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. F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local rhoA signaling in vivo. _Nature Communications_. 2016. Vol. 7, núm. 10493. [consulta: 21 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/155800]

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