BACKGROUND : Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and regulates the production of reactive oxygen species in macrophages. Selective genetic disruption of UCP2 in circulating leukocytes of LDLR(-/-) mice accelerated the formation of vulnerable plaque with excessive accumulation of macrophages. We therefore investigated whether the expression level of mitochondrial UCP2 influences the functional activities of circulating monocytes. RESULTS : Gene delivery of pcDNA encoding UCP2 to THP1 monocytes increased the amount of UCP2 protein 10 fold. The overexpression of UCP2 in THP1 monocytes significantly reduced expression levels of beta2 integrins (CD11a and CD11b) and adhesion molecules (VCAM-1 and ICAM-1). Accordingly, the chemokine-induced adhesion of THP1 monocytes on TNF-alpha-stimulated HAEC layer and ICAM-1-coated plate was markedly reduced by the UCP2 overexpression. Confocal image analysis after the staining with rhodamine-conjugated phalloidin showed that UCP2-overexpressed THP1 monocytes did not develope the cellular spreading triggered by the stimulation with TNF-alpha (10ng/ml/30min). Even though the functional expression level of CCR2, the dominant chemotaxis receptor on monocytes, was not affected by the overexpression of UCP2, the MCP-1-induced transmigration of monocytes through HAEC layer became less efficient by the UCP2 overexpression. When the controlled oxidative stress was given to THP1 monocytes by the incubation with 1-10 uM H2O2 for 1hour, transcripts of beta2-integrins(CD11a, CD11b, and, CD11c) and adhesion molecules (ICAM-1 and VCAM-1) in THP1 monocytes was increased significantly, which were all inhibited by the UCP2 overexpression. CONCLUSION : The enhanced expression of mitochondrial UCP2 in monocytes may prevent the excessive accumulation of monocytes/macrophages in the arterial wall, which is a prerequisite for the formation of vulnerable plaques.