HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

TNF-induced endothelial barrier disruption: beyond actin and Rho.

Abstract
The decrease of endothelial barrier function is central to the long-term inflammatory response. A pathological alteration of the ability of endothelial cells to modulate the passage of cells and solutes across the vessel underlies the development of inflammatory diseases such as atherosclerosis and multiple sclerosis. The inflammatory cytokine tumour necrosis factor (TNF) mediates changes in the barrier properties of the endothelium. TNF activates different Rho GTPases, increases filamentous actin and remodels endothelial cell morphology. However, inhibition of actin-mediated remodelling is insufficient to prevent endothelial barrier disruption in response to TNF, suggesting that additional molecular mechanisms are involved. Here we discuss, first, the pivotal role of Rac-mediated generation of reactive oxygen species (ROS) to regulate the integrity of endothelial cell-cell junctions and, second, the ability of endothelial adhesion receptors such as ICAM-1, VCAM-1 and PECAM-1, involved in leukocyte transendothelial migration, to control endothelial permeability to small molecules, often through ROS generation. These adhesion receptors regulate endothelial barrier function in ways both dependent on and independent of their engagement by immune cells, and orchestrate the crosstalk between leukocyte transendothelial migration and endothelial permeability during inflammation.
AuthorsB Marcos-Ramiro, D García-Weber, J Millán
JournalThrombosis and haemostasis (Thromb Haemost) Vol. 112 Issue 6 Pg. 1088-102 (Dec 2014) ISSN: 2567-689X [Electronic] Germany
PMID25078148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Actins
  • Cell Adhesion Molecules
  • Inflammation Mediators
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • rho GTP-Binding Proteins
Topics
  • Actins (metabolism)
  • Animals
  • Capillary Permeability
  • Cell Adhesion Molecules (metabolism)
  • Endothelial Cells (enzymology, immunology, metabolism, pathology)
  • Endothelium, Vascular (enzymology, immunology, metabolism, pathology)
  • Humans
  • Inflammation Mediators (immunology, metabolism)
  • Reactive Oxygen Species (metabolism)
  • Signal Transduction
  • Tumor Necrosis Factor-alpha (immunology, metabolism)
  • Vascular Remodeling
  • rho GTP-Binding Proteins (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: