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2016-01-27

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cc-by (c) Heemskerk, Niels et al., 2016
Please use this identifier to cite or link to this item: 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

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.

Subject

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

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

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Articles publicats en revistes (Ciències Fisiològiques)

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HEEMSKERK, Niels, et al. F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local rhoA signaling in vivo. Nature Communications. 2016. Vol. 7, num. 10493. ISSN 2041-1723. [consulted: 17 of August of 2026]. Available at: https://hdl.handle.net/2445/155800

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