Vascular Cell Adhesion Molecule-1 Expression and Signaling During Disease: Regulation by Reactive Oxygen Species and Antioxidants
- 15 September 2011
- journal article
- review article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 15 (6), 1607-1638
- https://doi.org/10.1089/ars.2010.3522
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. Antioxid. Redox Signal. 15, 1607–1638.Keywords
This publication has 329 references indexed in Scilit:
- Heparin II domain of fibronectin mediates contractility through an α4β1 co-signaling pathwayExperimental Cell Research, 2010
- VCAM‐1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis modelImmunology & Cell Biology, 2010
- Involvement of Galectin-3 with Vascular Cell Adhesion Molecule-1 in Growth Regulation of Mouse BALB/3T3 CellsOnline Journal of Public Health Informatics, 2009
- 18F-4V for PET–CT Imaging of VCAM-1 Expression in AtherosclerosisJACC: Cardiovascular Imaging, 2009
- Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma modelFree Radical Research, 2008
- Tocotrienols in health and disease: The other half of the natural vitamin E familyMolecular Aspects of Medicine, 2007
- Pulmonary CXCR2 regulates VCAM-1 and antigen-induced recruitment of mast cell progenitorsProceedings of the National Academy of Sciences of the United States of America, 2007
- Gαi2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasationProceedings of the National Academy of Sciences of the United States of America, 2007
- Genome sequence of the Brown Norway rat yields insights into mammalian evolutionNature, 2004
- The Pecking Order of Free Radicals and Antioxidants: Lipid Peroxidation, α-Tocopherol, and AscorbateArchives of Biochemistry and Biophysics, 1993