Elevated concentrations of nonesterified fatty acids increase monocyte expression of CD11b and adhesion to endothelial cells

Wei Yang Zhang, Eric Schwartz, Yingjie Wang, Jeanne Attrep, Zhi Li, Peter Reaven

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Objective - Monocyte proinflammatory activity has been demonstrated in obesity, insulin resistance, and type 2 diabetes, metabolic conditions that are frequently associated with elevated levels of nonesterified fatty acids (NEFA). We therefore tested the hypothesis that NEFA may induce monocyte inflammation. Methods and Results - Monocytes exposed to NEFA for 2 days demonstrated a dose-related increase in intracellular reactive oxygen species (ROS) formation and adhesion to endothelial cells. All of these effects were inhibited by the coaddition of antioxidants such as glutathione or butylated hydroxytoluene, by inhibition of ROS generation by NADPH oxidase inhibitors, and by inhibition of protein kinase C, a recognized stimulator of NAPDH oxidase. Monocytes exposed to NEFA also demonstrated a significant increase in CD11b message expression. Stimulation of monocyte adhesion to endothelial cells by NEFA was inhibited by addition of neutralizing antibodies to either CD11b or CD18. Finally, surface expression of CD11b increased significantly on monocytes as measured by flow cytometry, after their incubation with NEFA. Conclusion - These studies indicate that elevated concentrations of NEFA may enhance integrin facilitated monocyte adhesion to endothelial cells and these effects appear mediated, in part, through activation of NADPH oxidase and oxidative stress.

Original languageEnglish (US)
Pages (from-to)514-519
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Atherosclerosis
  • Integrins
  • Monocytes
  • Nonesterified fatty acids
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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