Endothelial Protrusions in Junctional Integrity and Barrier Function

Abstract

Endothelial cells of the microcirculation form a semi-permeable diffusion barrier between the blood and tissues. This permeability of the endothelium, particularly in the capillaries and postcapillary venules, is a normal physiological function needed for blood-tissue exchange in the microcirculation. During inflammation, microvascular permeability increases dramatically and can lead to tissue edema, which in turn can lead to dysfunction of tissues and organs. The molecular mechanisms that control the barrier function of endothelial cells have been under investigation for several decades, and remain an important topic due to the potential for discovery of novel therapeutic strategies to reduce edema. This review highlights current knowledge of the cellular and molecular mechanisms that lead to endothelial hyperpermeability during inflammatory conditions associated with injury and disease. This includes a discussion of recent findings demonstrating temporal protrusions by endothelial cells that may contribute to intercellular junction integrity between endothelial cells and affect the diffusion distance for solutes via the paracellular pathway.

A narrative review of changes in microvascular permeability after burn

“…The microvascular endothelial barrier is formed and maintained by the microvascular wall, which is composed of ECs, endothelial glycocalyx (EG), basement membrane (BM), and some auxiliary cells, which together constitute a single, tight, selective barrier (10).…”

“…Vascular ECs regulate various functions of blood vessels, including vascular smooth muscle tension, host defense response, angiogenesis, and tissue fluid hemostasis. Under the action of histamine, bradykinin, PAF, VEGF, and other inflammatory mediators or cytokines, the structural conformation of ECs changes to increase the permeability of the vascular endothelial barrier (10). The increased permeability of the vascular endothelial barrier leads to extravasation of blood components in the blood vessels, accumulation of albumin and plasma components in the interstitium, and the swelling or edema of interstitial tissues which is difficult to control.…”

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

“…The decrease in blood flow is a mechanical stimulus inducing the activation of the adhesion molecule PECAM, vascular endothelial growth factor (VEGF) receptors, and VE-cadherin, which results in the depolarization of the endothelial cell membrane and subsequent ROS generation. These events finally disrupt the integrity of the endothelial cell–cell junction and compromise the endothelial barrier, leading to hyperpermeability ( 141 ).…”

Intravital Imaging of Pulmonary Immune Response in Inflammation and Infection

“…Tabuchi et al demonstrated changes in pulmonary vessel diameters by injection of FITC-dextran into the jugular vein of mice (Tabuchi et al, 2008 ). Another study involved administration of intravenous FITC-albumin to enable measurement of microvascular leakage in rat mesentery through visualization of blood vessels (Alves et al, 2018 )In mice with GFP-labeled immune cell populations, blood vessels have been marked with Texas Red dextran for better contrast (Noda et al, 2014 ). Visualization of blood vessels and immune cells can be improved through application of novel labeling materials, proper combination of inflammation models, superior surgical methods, and advances in microscopic imaging.…”