1 Endothelial cell-to-cell junctions. Structural characteristics and functional role in the regulation of vascular permeability and leukocyte extravasation

Abstract

Endothelial monolayer forms the main barrier to the passage of macromolecules and circulating cells from blood to tissues. This property is regulated by intercellular junctions. These are complex structures formed by transmembrane adhesive molecules linked to a network of cytoplasmic cytoskeletal proteins. Endothelial junctions vary in number and organization along the vascular tree. Some transmembrane components of endothelial junctions have recently been identified. One is specifically expressed by endothelial cells (cadherin-5) while others (such as PECAM-1 and integrins) are also present in other cell types. The mechanisms that regulate the opening and the closure of endothelial junctions are still obscure. It is possible that inflammatory agents increase permeability by binding to specific receptors on the endothelial membrane. This would lead to the generation of intracellular signals causing cytoskeletal reorganization and opening of interendothelial gaps. This general sequence of events, however, seems to follow specific routes for different stimuli. In fact, permeability-increasing agents differ in the type of intracellular second messenger they trigger, for the time course of their effect, and for their specificity for the endothelium of different vascular districts. Endothelial junctions also regulate leukocyte extravasation. Endothelial cells actively contribute to this process by expressing adhesive molecules on their surface and by releasing chemotactic cytokines. Once leukocytes have adhered to the endothelium, a coordinated opening of interendothelial junctions occurs. The mechanism by which this takes place is unknown but it might resemble that triggered by soluble inflammatory mediators.