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


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.
Zhang
Wei-Yang
WY
Department of Medicine, Carl T. Hayden Veterans Affairs Medical Center, Phoenix, AZ 85012, USA. weiyang.zhang@med.va.gov
Schwartz
Eric
E
Wang
Yingjie
Y
Attrep
Jeanne
J
Li
Zhi
Z
Reaven
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism*; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D006801:Humans; D007948:Leukemia, Monocytic, Acute; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013552:Swine; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000975:Antioxidants; D039481:CD11b Antigen; D018821:CD18 Antigens; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D019255:NADPH Oxidases; D011493:Protein Kinase C