Objective-Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and regulates production of reactive oxygen species in macrophages. Previous studies have shown that selective genetic disruption of UCP2 in bone marrow cells results in excess accumulation of monocytes/macrophages in the vascular wall of hypercholesterolemic low-density lipoprotein receptor-deficient (LDLR Ϫ/Ϫ ) mice. Here we investigated whether UCP2 regulates expression of genes involved in monocyte recruitment. Methods and Results-UCP2 overexpression in THP1 monocytes, which induced a 10-fold increase in mitochondrial UCP2 protein levels, reduced steady-state level of intracellular reactive oxygen species (ROS) and H 2 O 2 -induced ROS production. THP1 monocytes with UCP2 overexpression showed lower intracellular calcium levels and less H 2 O 2 -triggered intracellular calcium mobilization, and less protein and mRNA levels of  2 integrins, most notably CD11b. UCP2 overexpression reduced  2 integrin-mediated firm adhesion of monocytes to either tumor necrosis factor-␣ (TNF-␣)-stimulated human aortic endothelial cell (HAEC) monolayers or to plates coated with intercellular adhesion molecule-1, not vascular cell adhesion molecule-1. UCP2 overexpression also inhibited cell spreading and actin polymerization in monocytes treated with TNF-␣ and monocyte chemoattractant protein-1 (MCP-1), and reduced MCP-1-induced transmigration of monocytes through HAEC monolayers. Key Words: UCP2 Ⅲ monocytes Ⅲ integrins Ⅲ adhesion Ⅲ atherosclerosis A therosclerosis exhibits features of chronic inflammatory diseases. 1 Macrophages that are derived from recruited monocytes accumulate in the atheroma from the earliest stage of atherogenesis and play pivotal roles in development of atherosclerosis. The process of monocyte recruitment is complex. E-and P-selectins are involved in the initial reversible adherence of monocytes to the endothelial cell layer. 2 The following irreversible firm adhesion is mediated by monocyte integrins that recognize vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. 3 Monocytes express both  1 (CD49d/CD29) and  2 integrins (CD11a/CD18, CD11b/ CD18, and CD11c/CD18). 3 Firm adhesion of monocytes requires activation of integrins, which can be triggered by agonist-induced activation of G protein-coupled chemokine receptors. 4 Monocytes express CC chemokine receptor 2 (CCR2), which binds monocyte chemoattractant protein-1 (MCP-1), leading to  integrin-mediated firm adhesion and subsequent transmigration of adhered monocytes through the vascular endothelium. 5 Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family, and is ubiquitously expressed in various tissues and by monocytes and macrophages. UCP2 is located on the mitochondrial inner membrane. Uncoupling process by mitochondrial UCP2 dissipates the proton electrochemical gradient that builds up across the mitochondrial membrane and results in reduced ATP synthesis, greater heat gene...
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