Overexpression of Uncoupling Protein 2 in THP1 Monocytes Inhibits β2 Integrin-Mediated Firm Adhesion and Transendothelial Migration

Je Won Ryu, Kyung Hee Hong, Jin Hee Maeng, Jae Bum Kim, Je Sang Ko, Joong Yeol Park, Ki Up Lee, Myeong Ki Hong, Seong Wook Park, You Ho Kim, Ki Hoon Han

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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-/-) 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 H2O 2-induced ROS production. THP1 monocytes with UCP2 overexpression showed lower intracellular calcium levels and less H2O 2-triggered intracellular calcium mobilization, and less protein and mRNA levels of β2 integrins, most notably CD11b. UCP2 overexpression reduced β2 integrin-mediated firm adhesion of monocytes to either tumor necrosis factor-α (TNF-α)-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-α and monocyte chemoattractant protein-1 (MCP-1), and reduced MCP-1-induced transmigration of monocytes through HAEC monolayers. Conclusions-Mitochondrial UCP2 in circulating monocytes may prevent excessive accumulation of monocytes/macrophages in the arterial wall, thereby reducing atherosclerotic plaque formation.

Original languageEnglish
Pages (from-to)864-870
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number5
DOIs
Publication statusPublished - 2004 May 1
Externally publishedYes

Keywords

  • Adhesion
  • Atherosclerosis
  • Integrins
  • Monocytes
  • UCP2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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