Lysophosphatidylcholine (LPC) attenuates macrophage-mediated oxidation of LDL.
We have previously shown that paraoxonase 1 action on macrophages produced lysophosphatidylcholine (LPC) and significantly decreased cell-mediated LDL oxidation. Thus, in the present study, we questioned whether LPC can directly inhibit macrophage-mediated oxidation of LDL. Addition of increasing LPC concentrations (0-5 microM) to J774A.1 macrophages, mouse peritoneal macrophages (MPM), or to human monocytes-derived macrophages (HMDM) resulted in up to 83%, 67%, and 75% inhibition in cell-mediated oxidation of LDL, respectively. The mechanism for this LPC effect involves up to 60% inhibition of superoxide anion release from MPM in response to phorbol ester (PMA), 26% inhibition of PMA-induced NADPH oxidase activation (p47phox translocation from the cytosol to the plasma membrane), and a 2-fold stimulation of the macrophage paraoxonase 2 (PON2) lactonase activity. We thus conclude that inhibition of macrophage-mediated oxidation of LDL by LPC can contribute to attenuation of macrophage foam cell formation and atherosclerotic lesion development.
Rosenblat
Mira
M
The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel.
Oren
Roni
R
Aviram
Michael
M
D000818:Animals; D043303:Aryldialkylphosphatase / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010703:Phorbol Esters; D013481:Superoxides; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D043303:Aryldialkylphosphatase