Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury

• Published in: Tissue barriers Vol. 3; no. 1-2; p. e974448
• Main Authors: Kása, Anita, Csortos, Csilla, Verin, Alexander D
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2015
• Subjects: acute lung injury; AJ, adherens junction; ALI, Acute Lung Injury; ARDS, Acute Respiratory Distress Syndrome; barrier function; CaD, caldesmon; calmodulin (CaM) dependent MLC kinase; CPI-17, PKC potentiated inhibitory protein of 17 kDa; cytoskeleton; EC, endothelial cells; endothelial junctions; GJ, gap junction; HSP-27, small heat shock actin-capping protein of 27 kDa; IL, interleukin; LPS, lipopolysaccharide; MLC, myosin light chain; MLCK, Ca; MLCP, myosin light chain phosphatase; MT, microtubules; MYPT1, myosin phosphatase targeting subunit 1; PKA, protein kinase A; PKC, protein kinase C; pulmonary endothelium; Review; SM, smooth muscle; thrombin; TJ, tight junction; TLR4, toll-like receptor 4; TNFα, tumor necrosis factor α; TJ, tight junction; thrombin; ARDS, Acute Respiratory Distress Syndrome; TNFα, tumor necrosis factor α; acute lung injury; endothelial junctions; MLCP, myosin light chain phosphatase; SM, smooth muscle; TLR4, toll-like receptor 4; MLCK, Ca2+/calmodulin (CaM) dependent MLC kinase; barrier function; HSP-27, small heat shock actin-capping protein of 27 kDa; PKC, protein kinase C; cytoskeleton; pulmonary endothelium; MLC, myosin light chain; MYPT1, myosin phosphatase targeting subunit 1; ALI, Acute Lung Injury; EC, endothelial cells; AJ, adherens junction; CPI-17, PKC potentiated inhibitory protein of 17 kDa; GJ, gap junction; IL, interleukin; LPS, lipopolysaccharide; MT, microtubules; PKA, protein kinase A; CaD, caldesmon
• ISSN: 2168-8362; 2168-8370; 2168-8370
• DOI: 10.4161/21688370.2014.974448

Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review.