IN-VITRO OXIDIZED HDL EXERTS A CYTOTOXIC EFFECT ON MACROPHAGES

The cytotoxic effect of native high density lipoprotein (n-HDL) and ox idised high density lipoprotein (ox-HDL) on macrophages was studied an d compared with that of low density lipoprotein (LDL). Copper-mediated oxidation of HDL and LDL was conducted in vitro and assessed by the a nalysis of conjugated dienes (CD). The kinetics of CD production durin g lipoprotein oxidation showed that HDL, relative to LDL, exhibited a shorter lag phase (47.7 +/- 17.8 vs. 82.9 +/- 24.5 min), higher diene production (242.2 +/- 23.0 vs. 210.4 +/- 14.9 nmol/mg lipid) and reach ed maximal diene concentration in less time (100.0 +/- 35.4 vs. 136.4 +/- 27.9 min). The maximal rate of CD production was 5.38 +/- 1.30 nmo l/mg lipid/min for HDL and 4.42 +/- 0.60 nmol/mg lipid/min for LDL. Vi tamin E concentration was higher in HDL than in LDL (2.76 +/- 0.41 vs. 2.19 +/- 0.33 mu g alpha-tocopherol equivalents/mg lipid). Ox-HDL and oxidised LDL (ox-LDL), under the same experimental conditions, were c ytotoxic to macrophages in a dose-dependent manner. At the same protei n, or total mass concentration, ox-HDL was less cytotoxic than ox-LDL. However, when both lipoproteins were compared at the same lipid or ch olesterol concentrations, ox-HDL was equally or more cytotoxic than ox -LDL. In conclusion; HDL is more susceptible to in vitro oxidation tha n LDL and the resultant modification of HDL converts this lipoprotein into a cytotoxic particle.