Vascular Cell Adhesion Molecule-1 Expression and Signaling During Disease: Regulation by Reactive Oxygen Species and Antioxidants

Abstract

The endothelium is immunoregulatory in that inhibiting the function of vascular adhesion molecules blocks leukocyte recruitment and thus tissue inflammation. The function of endothelial cells during leukocyte recruitment is regulated by reactive oxygen species (ROS) and antioxidants. In inflammatory sites and lymph nodes, the endothelium is stimulated to express adhesion molecules that mediate leukocyte binding. Upon leukocyte binding, these adhesion molecules activate endothelial cell signal transduction that then alters endothelial cell shape for the opening of passageways through which leukocytes can migrate. If the stimulation of this opening is blocked, inflammation is blocked. In this review, we focus on the endothelial cell adhesion molecule, vascular cell adhesion molecule-1 (VCAM-1). Expression of VCAM-1 is induced on endothelial cells during inflammatory diseases by several mediators, including ROS. Then, VCAM-1 on the endothelium functions as both a scaffold for leukocyte migration and a trigger of endothelial signaling through NADPH oxidase-generated ROS. These ROS induce signals for the opening of intercellular passageways through which leukocytes migrate. In several inflammatory diseases, inflammation is blocked by inhibition of leukocyte binding to VCAM-1 or by inhibition of VCAM-1 signal transduction. VCAM-1 signal transduction and VCAM-1-dependent inflammation are blocked by antioxidants. Thus, VCAM-1 signaling is a target for intervention by pharmacological agents and by antioxidants during inflammatory diseases. This review discusses ROS and antioxidant functions during activation of VCAM-1 expression and VCAM-1 signaling in inflammatory diseases.

Two Faces of Vitamin E in the Lung

“…In contrast to the report of 1.4 mM plasma g-tocopherol in China (Figure 1B), another report indicates an average of 2.4 mM plasma g-tocopherol for a small group of tin miners in China (52), but it is not known whether tocopherol levels in this group of individuals differ from other areas in China. In the United States, the average human plasma g-tocopherol levels are two to five times higher than those of many European and Asian countries (Figure 1B), whereas the average human plasma a-tocopherol levels are relatively similar among these countries (28). This fivefold higher level of human plasma g-tocopherol is similar to the fivefold increase in plasma g-tocopherol in mice that increased allergic lung inflammation with g-tocopherol administration (8).…”

“…Moreover, g-tocopherol elevated lung eosinophil recruitment by 175%, and a-tocopherol reduced lung eosinophil recruitment by 65% (8). Interestingly, g-tocopherol negated the antiinflammatory benefit of a-tocopherol (8,28). In these mice, a-tocopherol blocked and g-tocopherol increased airway hyperresponsiveness (8).…”

“…We have previously provided rationale to explain these conflicting outcomes based on our observation of the differences of levels of vitamin E isoforms present in the study supplements, vehicles, and diets (6,28,29). We have additionally demonstrated opposing regulatory functions of a-tocopherol and g-tocopherol in mice and the mechanisms for anti-and proinflammatory functions of these tocopherols (7,8,28,30,31). …”

Characterization of Human Aortic Endothelial Cells, Endothelial Progenitor Cells, and Cardiomyocytes

“…ROS upregulate VCAM-1 expression in endothelial cells [30]; however, this was not observed in HCMs. H 2 O 2 increases the secretion of ICAM-1 in canine myocytes [31], which is consistent with the results of the present study.…”

Methods of Endothelial Function Assessment: Description and Applications

“…63 VCAM-1 also belongs to the immunoglobulin supergene family and is ligand to the very late antigen-4, a β-integrin found on the surface of mononuclear cells. 64 VCAM-1 expression is restricted to endothelial cells and occasional fusiform cells. In contrast to ICAM-1, which is produced in low concentrations, VCAM-1 is not expressed on healthy endothelial cells.…”