Active participation of endothelial cells in inflammation

Abstract

Leukocyte migration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules and then migrate across the vascular endothelium. Endothelial cell adhesion molecules and their counter-receptors on leukocytes generate intracellular signals. This review focuses on the active function of endothelial cells during leukocyte-endothelial cell interactions. We include a discussion of the "outside-in" signals in endothelial cells, which are stimulated by antibody cross-linking or leukocyte binding to platelet-endothelial cell adhesion molecule-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Some of these signals in endothelial cells have been demonstrated to actively participate in leukocyte migration. We suggest that some of the adhesion molecule signals, which have not been assigned a function, are consistent with signals that stimulate retraction of lateral junctions, stimulate endothelial cell basal surface adhesion, or induce gene expression.

Fig. 1

Stimulation of ICAM-1 and VCAM-1 activates “outside-in” signals, which are required for leukocyte migration. Intracellular calcium or PKC in brain endothelial cells is necessary for ICAM-1-dependent lymphocyte migration but not lymphocyte adhesion [46]. Antibody cross-linking of VCAM-1 or lymphocyte binding to VCAM-1 activates release of intracellular calcium, calcium channels, and Rac1, which are required for the VCAM-1 activation of endothelial cell nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [61]. This stimulation of NADPH oxidase is required for the VCAM-1-dependent activation of endothelial cell-associated matrix metalloproteinases (MMPs) [63]. VCAM-1-dependent lymphocyte migration requires VCAM-1-stimulated endothelial cell NADPH oxidase and endothelial cell-associated MMPs [60, 63]. ROS, Reactive oxygen species; JAMs, junctional adhesion molecules.