TOXICITY OF OXIDIZED LOW-DENSITY-LIPOPROTEIN TOWARDS MOUSE PERITONEAL-MACROPHAGES INVITRO

The addition of cupric sulphate-oxidised low density lipoprotein (oxLDL) to mouse peritoneal macrophage (MPM) cultures caused toxicity towards the cells, measured by tritiated adenine release. The degree of toxicity increased with increasing concentrations of oxLDL up to 18 h incubation with MPM, after which the toxicity appeared to be independent of the concentration of oxLDL used. Toxicity was significantly reduced when vitamin E in the form of D,L-alpha-tocopherol was added to the LDL before the artificial oxidation, but vitamin E had no effect on the toxicity when added alongside the oxLDL in the culture medium. However, if the MPM were pre-incubated for 24 h with 80 muM vitamin E, there was a significant reduction in the level of toxicity up to 6 h in culture with oxLDL. There was a strong correlation (r = 0.81) between the degree of oxidation of the LDL, measured as thiobarbituric-reactive substances, and the corresponding toxicity. This indicated that the more oxidised the LDL was, the more toxic it was to the macrophages. Native LDL also led to toxicity, but only after a time-lag of 20 h. Again, this toxicity was decreased by pre-incubation of the MPM with vitamin E, but not by addition of vitamin E at the same time as LDL. The findings suggest that oxLDL is capable of contributing to the onset of necrosis during atherogenesis and that the oxidative capacity of the macrophage foam cells themselves might contribute to the process.