Macrophages can decrease the level of cholesteryl ester hydroperoxides in low density lipoprotein.
Murine and human macrophages rapidly decreased the level of cholesteryl ester hydroperoxides in low density lipoprotein (LDL) when cultured in media non-permissive for LDL oxidation. This process was proportional to cell number but could not be attributed to the net lipoprotein uptake. Macrophage-mediated loss of lipid hydroperoxides in LDL appears to be metal ion-independent. Degradation of cholesteryl linoleate hydroperoxides was accompanied by accumulation of the corresponding hydroxide as the major product and cholesteryl keto-octadecadienoate as a minor product, although taken together these products could not completely account for the hydroperoxide consumption. Cell-conditioned medium possessed a similar capacity to remove lipid hydroperoxides as seen with cellular monolayers, suggesting that the activity is not an integral component of the cell but is secreted from it. The activity of cell-conditioned medium to lower the level of LDL lipid hydroperoxides is associated with its high molecular weight fraction and is modulated by the availability of free thiol groups. Cell-mediated loss of LDL cholesteryl ester hydroperoxides is facilitated by the presence of alpha-tocopherol in the lipoprotein. Together with our earlier reports on the ability of macrophages to remove peroxides rapidly from oxidized amino acids, peptides, and proteins as well as to clear selectively cholesterol 7-beta-hydroperoxide, results presented in this paper provide evidence of a potential protective activity of the cell against further LDL oxidation by removing reactive peroxide groups in the lipoprotein.
Baoutina
A
A
Cell Biology Group, The Heart Research Institute, Camperdown, New South Wales 2050, Australia. a.baoutina@hri.org.au
Dean
R T
RT
Jessup
W
W
D000818:Animals; D002452:Cell Count; D002460:Cell Line; D002478:Cells, Cultured; D002614:Chelating Agents / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000378:metabolism; D003553:Cystine / Q000494:pharmacology; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000378:metabolism
D002614:Chelating Agents; D002788:Cholesterol Esters; D003470:Culture Media; D006878:Hydroxides; D008077:Lipoproteins, LDL; D014810:Vitamin E; C081459:cholesteryl ester hydroperoxide; D003553:Cystine