Elevated concentrations of nonesterified fatty acids increase monocyte expression of CD11b and adhesion to endothelial cells.
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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. CONCLUSIONS: 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.
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In vitro studies have implicated these lipids (and in some experiments lipolysis of triglyceride) in inflammation, expression of adhesion molecules, and promotion of coagulation.
“In vitro studies have implicated these lipids (and in some experiments lipolysis of triglyceride) in inflammation (147), expression of adhesion molecules (148), and promotion of coagulation (149).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [147]
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- Authors
- Zhang, W.-Y., Schwartz, E., Wang, Y., Attrep, J., Li, Z., & Reaven, P.
- Affiliations
- Carl T. Hayden Veterans Affairs Medical Center (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2006-03
- Volume
- 26
- Issue
- 3
- Pages
- 514-519
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2116862225
- Cited by
- 70
- References
- 21
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 6 · 2012: 5
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Office of Research and Development
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- free fatty acids, monocytes, CD11b, monocyte adhesion, endothelial cells, reactive oxygen species, NADPH oxidase, oxidative stress, protein kinase C, integrins, CD18, inflammation, obesity, insulin resistance, type 2 diabetes
- MeSH terms
- Animals, Antibodies, Monoclonal, Antioxidants, Aorta, Cell Adhesion, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Fatty Acids, Nonesterified, Humans, Leukemia, Monocytic, Acute, Monocytes, Protein Kinase C, Swine, Vasculitis, Oxidative Stress, CD18 Antigens, NADPH Oxidases, CD11b Antigen, Endothelial Cells, Cell Line, Tumor, Atherosclerosis
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