title: Cholesterol metabolism in the macrophage. I. The regulation of cholesterol exchange.
abstract: The cholesterol metabolism of homogeneous populations of mouse peritoneal macrophages was evaluated under in vitro conditions. Macrophages are rich in free cholesterol and maintain a constant cholesterol to protein ratio (12 microg cholesterol/mg protein). No detectable cholesterol ester was present within the cell. More than 95% of total cholesterol was membrane associated and the majority was present in subcellular fractions containing lysosomes and plasma membrane. Less than 0.1% of cell cholesterol was synthesized from acetate-1-(14)C. During in vitro cultivation, macrophages rapidly exchanged their membrane cholesterol with that of lipoproteins of calf serum. About 30% of the cell cholesterol was exchanged per hour in 20% serum medium, and exchange was nearly complete by 5 hr. Exchange proceeded in a rapid exponential phase followed by a slower phase. Calculations based on a two compartment model indicated that the rapidly exchanging cholesterol compartment represented 60-70% of the total cell cholesterol, and the slowly exchanging compartment accounted for 30-40%. The relationship between serum lipoprotein concentration and exchange rate exhibited first-order kinetics. The rate was determined by thermal energy, in keeping with a Q(10) of 2, and an activation energy of 12 kcal/mole. Exchange was independent of bulk transport of lipoproteins by pinocytosis and phagocytosis, and was not linked to energy metabolism. The alpha-lipoproteins were the major class of proteins of calf serum participating in exchange.
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D001797:Blood Protein Electrophoresis; D002478:Cells, Cultured; D002498:Centrifugation; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004952:Esters / Q000032:analysis; D066298:In Vitro Techniques; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D013347:Subcellular Fractions / Q000378:metabolism; D013696:Temperature; D014316:Tritium
chemical_list: D004952:Esters; D008074:Lipoproteins; D014316:Tritium; D002784:Cholesterol; D000135:Acid Phosphatase