title: Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading.
abstract: The influence of the hypercholesterolemia associated with atherosclerosis on monocytes is poorly understood. Monocytes are exposed to high concentrations of lipids, particularly cholesterol and lysophosphatidylcholine (lyso-PC). Indeed, in line with recent reports, we found that monocytes accumulate cholesteryl esters (CEs) in hypercholesterolemic mice, demonstrating the need for studies that analyze the effects of lipid accumulation on monocytes. Here we analyze the effects of cholesterol and lyso-PC loading in human monocytes and macrophages. We found that cholesterol acyltransferase and CE hydrolase activities are lower in monocytes. Monocytes also showed a different expression profile of cholesterol influx and efflux genes in response to lipid loading and a different pattern of lyso-PC metabolism. In monocytes, increased levels of CE slowed the conversion of lyso-PC into PC. Interestingly, although macrophages accumulated glycerophosphocholine, phosphocholine was the main water-soluble choline metabolite being generated in monocytes, suggesting a role for mono- and diacylglycerol in the chemoattractability of these cells. In summary, monocytes and macrophages show significant differences in lipid metabolism and gene expression profiles in response to lipid loading. These findings provide new insights into the mechanisms of atherosclerosis and suggest potentials for targeting monocyte chemotactic properties not only in atherosclerosis but also in other diseases.
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827.
authors.forename: Irene
authors.initials: I
authors.lastname: Fernandez-Ruiz
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Puchalska
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827.
authors.forename: Chandrakala Aluganti
authors.initials: CA
authors.lastname: Narasimhulu
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827.
authors.forename: Bhaswati
authors.initials: B
authors.lastname: Sengupta
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827 spartha@ucf.edu.
authors.forename: Sampath
authors.initials: S
authors.lastname: Parthasarathy
mesh_terms: D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D008244:Lysophosphatidylcholines; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase; D002794:Choline
keywords: atherosclerosis; dyslipidemias; foam cells; glycerophosphocholine; lysophosphatidylcholine; lysophospholipid; phosphocholine
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