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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

Nyckelord

Antioxidants/metabolism

Cells

Cultured

Humans

Isoenzymes/metabolism

Lipoproteins

LDL/*pharmacology

Macrophages/*drug effects/*metabolism

Oxidation-Reduction/drug effects

Reactive Oxygen Species/metabolism

Superoxide Dismutase/metabolism

Antioxidants/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)