Vascular endothelial cells form a barrier between the blood or lymph at the apical side and the intima at the basolateral side. The endothelium is a single cell-thick sheet of endothelial cells with adjacent cells held together by junctional complexes. These complexes are composed of transmembrane adhesion proteins that mediate intercellular adhesion and are stabilized through interactions with the cytoskeleton.
Tight junctions are located near the apical surface of endothelial cells and are key to the barrier function of the endothelium. They prevent the passage of fluid, ions, and larger molecules from one side of the barrier to the other. Adherens junctions provide additional adhesive strength and are typically localized more toward the basolateral face of the epithelium. Adherens junction proteins transmit multiple signals into the cell and can regulate the signaling properties of other cell surface proteins. Focal adhesion complexes anchor endothelial cells to the extracellular matrix and also transduce signals into the cell. The control of focal adhesion function is important for regulating cell migration.
During inflammation, activated endothelial cells upregulate additional adhesion proteins on their apical face. These proteins mediate the rolling and tethering of circulating leukocytes to the endothelium. Leukocyte transmigration across the endothelium requires the regulated detachment of adhesion complex associations which allows leukocytes to reach the intima without disrupting endothelial barrier function.