Human macrophages limit oxidation products in low density lipoprotein.
This study tested the hypothesis that human macrophages have the ability to modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular antioxidant defence system. While many studies have focused on macrophage LDL oxidation in atherosclerosis development, less attention has been given to the cellular antioxidant capacity of these cells. Compared to cell-free controls (6.2 +/- 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 +/- 0.4 nmol/mg LDL after 24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were 3.69 +/- 0.5 nmol/mg LDL in cell-free media, and 2.48 +/- 0.9 nmol/mg LDL in the presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7 +/- 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to cell-free incubation (105.0 +/- 14.1 nmol/mg LDL) (P = 0.005). The levels of lipid peroxides in oxLDL were 137.9 +/- 59.9 nmol/mg LDL and in cell-free media 242 +/- 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016). The increased levels of glutathione in oxLDL-treated macrophages were accompanied by enhanced catalase and glutathione peroxidase activities. Our results suggest that macrophages respond to oxidative stress by endogenous antioxidant activity, which is sufficient to decrease reactive oxygen species both in LDL and oxLDL. This may suggest that the antioxidant activity is insufficient during atherosclerosis development. Thus, macrophages may play a dual role in atherogenesis, i.e. both by promoting and limiting LDL-oxidation.
Hultén
Lillemor Mattsson
LM
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. Lillemor.Mattsson@wlab.gu.se
Ullström
Christina
C
Krettek
Alexandra
A
van Reyk
David
D
Marklund
Stefan L
SL
Dahlgren
Claes
C
Wiklund
Olov
O
D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D007527:Isoenzymes; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D013482:Superoxide Dismutase
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