on December 15, 2005
Published online before print December 15, 2005, doi: 10.1161/01.ATV.0000200226.53994.09
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 17, 2005
Accepted on December 2, 2005
Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells
Wei-Yang Zhang *;
From the Department of Medicine (W.-Y.Z., E.S., Y.W., J.A., P.R.), Section of Metabolism, Endocrinology and Nutrition, Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Ariz; and The Biodesign Institute at Arizona State University (Z.L.), Tempe, Ariz.
* To whom correspondence should be addressed. E-mail: weiyang.zhang{at}med.va.gov.
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.
Key words: atherosclerosis • integrins • monocytes • nonesterified fatty acids • reactive oxygen species
This article has been cited by other articles:
 |
|
 |
|
  P. A. Permana, W. Zhang, M. Wabitsch, P. Fischer-Posovszky, W. C. Duckworth, and P. D. Reaven Pioglitazone reduces inflammatory responses of human adipocytes to factors secreted by monocytes/macrophages Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E1076 - E1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-Y. Zhang, E. A. Schwartz, P. A. Permana, and P. D. Reaven Pioglitazone Inhibits the Expression of Inflammatory Cytokines From Both Monocytes and Lymphocytes in Patients With Impaired Glucose Tolerance Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2312 - 2318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Alipour, A. J.H. H.M van Oostrom, A. Izraeljan, C. Verseyden, J. M. Collins, K. N. Frayn, T. W.M. Plokker, J. W. F. Elte, and M. Castro Cabezas Leukocyte Activation by Triglyceride-Rich Lipoproteins Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 792 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hagita, M. Osaka, K. Shimokado, and M. Yoshida Oxidative Stress in Mononuclear Cells Plays a Dominant Role in Their Adhesion to Mouse Femoral Artery After Injury Hypertension, March 1, 2008; 51(3): 797 - 802. [Abstract] [Full Text] [PDF]
|
|