CD11c/CD18 Expression Is Upregulated on Blood Monocytes During Hypertriglyceridemia and Enhances Adhesion to Vascular Cell Adhesion Molecule-1

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 31; no. 1; pp. 160 - 166
• Main Authors: Gower, R. Michael, Wu, Huaizhu, Foster, Greg A., Devaraj, Sridevi, Jialal, Ishwarlal, Ballantyne, Christie M., Knowlton, Anne A., Simon, Scott I.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2011; Lippincott Williams & Wilkins
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biological Transport; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; CD11c Antigen - blood; CD18 Antigens - blood; Cell Adhesion; Dietary Fats - administration & dosage; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Hypertriglyceridemia - blood; Hypertriglyceridemia - etiology; Hypertriglyceridemia - immunology; Inflammation - blood; Inflammation - etiology; Inflammation - immunology; Lipoproteins - blood; Low Density Lipoprotein Receptor-Related Protein-1 - blood; Male; Medical sciences; Microfluidic Analytical Techniques; Monocytes - immunology; Postprandial Period; Time Factors; Triglycerides - blood; Up-Regulation; Vascular Cell Adhesion Molecule-1 - metabolism; Vertebrates: cardiovascular system; Vascular cell adhesion molecule 1; Monocyte; Leukocyte; Metabolic diseases; Lipids; Cardiovascular disease; Hyperlipoproteinemia; Lipoprotein; Triglyceride; Enzymopathy; Vascular disease; Hypertriglyceridemia; adhesion molecules; Atherosclerosis; leukocytes; Dyslipemia
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.110.215434

OBJECTIVE—Atherosclerosis is associated with monocyte adhesion to the arterial wall that involves integrin activation and emigration across inflamed endothelium. Involvement of β2-integrin CD11c/CD18 in atherogenesis was recently shown in dyslipidemic mice, which motivates our study of its inflammatory function during hypertriglyceridemia in humans. METHODS AND RESULTS—Flow cytometry of blood from healthy subjects fed a standardized high-fat meal revealed that at 3.5 hours postprandial, monocyte CD11c surface expression was elevated, and the extent of upregulation correlated with blood triglycerides. Monocytes from postprandial blood exhibited an increased light scatter profile, which correlated with elevated CD11c expression and uptake of lipid particles. Purified monocytes internalized triglyceride-rich lipoproteins isolated from postprandial blood through low-density lipoprotein–receptor–related protein-1, and this also elicited CD11c upregulation. Laboratory-on-a-chip analysis of whole blood showed that monocyte arrest on a vascular cell adhesion molecule-1 (VCAM-1) substrate under shear flow was elevated at 3.5 hours and correlated with blood triglyceride and CD11c expression. At 7 hours postprandial, blood triglycerides decreased and monocyte CD11c expression and arrest on VCAM-1 returned to fasting levels. CONCLUSION—During hypertriglyceridemia, monocytes internalize lipids, upregulate CD11c, and increase adhesion to VCAM-1. These data suggest that analysis of monocyte inflammation may provide an additional framework for evaluating individual susceptibility to cardiovascular disease.