Chemicals in diesel exhaust particles generate reactive oxygen radicals and induce apoptosis in macrophages

There is increasing evidence that particulate air pollutants, such as diese l exhaust particles (DEP), potentiate chronic inflammatory processes as wel l as acute symptomatic responses in the respiratory tract. The mechanisms o f action as well as the cellular targets for DEP remain to be elucidated. W e show in this paper that the phagocytosis of DEP by primary alveolar macro phages or macrophage cell lines, RAW 264.7 and THP-1, leads to the inductio n of apoptosis through generation of reactive oxygen radicals (ROR), This o xidative stress initiates two caspase cascades and a series of cellular eve nts, including lass of surface membrane asymmetry and DNA damage. The apopt otic effect on macrophages is cell specific, because DEP did not induce sim ilar effects in nonphagocytic cells, DEP that had their organic constituent s extracted were no longer able to induce apoptosis or generate ROR, The or ganic extracts were, however, able to induce apoptosis. DEP chemicals also induced the activation of stress-activated protein kinases, which play a ro le in cellular apoptotic pathways. The injurious effects of native particle s or DEP extracts on macrophages could be reversed by the antioxidant, N-ac etyl-cyteine. Taken together, these data suggest that organic compounds con tained in DEP may exert acute toxic effects via the generation of ROR in ma crophages.