Oxidative modification of low density lipoprotein by diesel exhaust particles

Oxidized low density lipoprotein (LDL) has a variety of hazardous influences on biological systems. Oxidative modification of LDL by diesel exhaust particles (DEP) was studied in vitro to assess its in vivo health effects. DEP suspensions (1, 10 and 100 micrograms/ml) were incubated for 1 h with LDL (1 mg protein/ml) at 37 degrees C. Conjugated diene formation and negative charges in LDL were increased by DEP-treatment in a dose-dependent manner. When native LDL and DEP-treated LDL (DEP-LDL) were incubated for 18 h with macrophage, J774A.1 cell at 37 degrees C, significantly more DEP-LDL was taken up into cells than native LDL. Accumulation of cholesterol ester in cells incubated with DEP-LDL was 4 to 8 times higher than that with native LDL while there was no significant difference between them in free cholesterol content. Incubation (18 h) of J774A.1 with DEP-LDL caused an increase in leakage of lactate dehydrogenase from cells in a DEP-concentration dependent manner, but the incubation with native LDL or DEP per se did not increase the leakage except at the highest concentration of DEP. These results suggest that DEP oxidatively modified LDL giving it cytotoxic, inflammatory and atherogenic properties characteristic of so-called oxidized LDL; these initial modifications of LDL may be one of the underlying mechanisms for diseases associated with DEP.