Cell-induced copper ion-mediated low density lipoprotein oxidation increases during in vivo monocyte-to-macrophage differentiation.
Macrophage activation is associated with the production and release of reactive oxygen species (ROS), which are capable of mediating oxidative modification of low-density lipoprotein (LDL). In the present study we questioned whether cellular capacity to oxidize LDL increases during in vivo monocyte/macrophage maturation. We developed a novel model for macrophage maturation in vivo using mouse peritoneal macrophages (MPMs) harvested at increasing intervals after intraperitoneal thioglycollate injection. Macrophage maturation was evidenced by a progressive increase in cellular size, density, granulation, and expression of cell surface markers CD11b and CD36, and by a gradual decrement in myeloperoxidase activity. Cellular capacity to stimulate copper ion-mediated oxidation of LDL increased gradually by up to 2-fold during in vivo macrophage maturation in Balb/C mice, similar to the pattern observed during 1,25-dihydroxyvitamin D3-induced in vitro differentiation of the PLB-985 cell line. These effects were attributed to a gradual increase in production of ROS by up to 9-fold. The mechanism for the increase in cellular oxidative stress during macrophage maturation could be related, at least in part, to NADPH oxidase activation, as demonstrated by a gradual increase over time in p47phox expression (mRNA and protein) and in its translocation to the plasma membrane. In conclusion, in vivo monocyte-to-macrophage differentiation is associated with increased cell capacity to oxidize LDL, which may represent a protective mechanism for rapid removal of atherogenic LDL from extracellular spaces in the arterial wall.
Fuhrman
Bianca
B
Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel 31096. fuhrman@tx.technion.ac
Shiner
Maayan
M
Volkova
Nina
N
Aviram
Michael
M
D000818:Animals; D000838:Anions / Q000378:metabolism; D001158:Arteries / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis / Q000378:metabolism; D018955:CD36 Antigens / Q000096:biosynthesis / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D003300:Copper / Q000378:metabolism*; D004950:Esterases / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007477:Ions / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010537:Peritoneum / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides; D013864:Thioglycolates / Q000378:metabolism; D013997:Time Factors
D000838:Anions; D039481:CD11b Antigen; D018955:CD36 Antigens; D007477:Ions; D008077:Lipoproteins, LDL; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D013864:Thioglycolates; D013481:Superoxides; D003300:Copper; D009195:Peroxidase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D004950:Esterases; D002117:Calcitriol; D010100:Oxygen