Chemicals in Diesel Exhaust Particles Generate Reactive Oxygen Radicals and Induce Apoptosis in Macrophages

Abstract

There is increasing evidence that particulate air pollutants, such as diesel exhaust particles (DEP), potentiate chronic inflammatory processes as well as acute symptomatic responses in the respiratory tract. The mechanisms of action as well as the cellular targets for DEP remain to be elucidated. We show in this paper that the phagocytosis of DEP by primary alveolar macrophages or macrophage cell lines, RAW 264.7 and THP-1, leads to the induction of apoptosis through generation of reactive oxygen radicals (ROR). This oxidative stress initiates two caspase cascades and a series of cellular events, including loss of surface membrane asymmetry and DNA damage. The apoptotic effect on macrophages is cell specific, because DEP did not induce similar effects in nonphagocytic cells. DEP that had their organic constituents extracted were no longer able to induce apoptosis or generate ROR. The organic extracts were, however, able to induce apoptosis. DEP chemicals also induced the activation of stress-activated protein kinases, which play a role in cellular apoptotic pathways. The injurious effects of native particles or DEP extracts on macrophages could be reversed by the antioxidant, N-acetyl-cysteine. Taken together, these data suggest that organic compounds contained in DEP may exert acute toxic effects via the generation of ROR in macrophages.

Motorcycle Exhaust Particles Induce Airway Inflammation and Airway Hyperresponsiveness in BALB/C Mice

“…The exhaust emitted from two-stroke motorcycle engines contained more hydrocarbons, both in quantity and species, than the diesel fuel (Chan and Nien, 1995;Jemma et al 1995). Studies also showed that although the chemical composition of MEP, in terms of PAH content, is similar to that of DEP, the percentages are different (Barfknecht et al, 1982;Hiura et al, 1999;Ueng et al, 2000). The PAHs composition found in DEP was: phenanthrene 52%, fluorenes 15%, naphthalene 13%, pyrene 10%, and fluoranthene 10% (Barfknecht et al 1982), and the composition found in MEP was: naphthalene 68%, anthracene 5%, acenaphthylene 4%, acenaphthene 4%, pyrene 4%, fluorine, 3%, fluoranthene 2%, and others 10%) (Ueng et al, 2000).…”

Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment

“…Recognizing the unique role of the mitochondria in energy metabolism and being a major target during energy depletion, it is not just hypothetical to link energy degeneration to mitochondria dysfunction. There are adequate evidences to support mitochondrial damage as a key event associated with chemical toxicity [144] , [145] , [10] , [146] , [147] . During pathological and ultrastructural damage in heart, mitochondrial swelling and cristae disorder was observed by Li et al [145] and in human SII-SYSY cells by Wang et al [146] .…”

“…Wei et al [148] also found abnormal alterations of alveolar macrophage mitochondrial structure such as swelling, cristae disorder, and vacuolation. Decreased mitochondrial membrane potential and increased O 2 radical could initiate apoptosis and down regulate ATP generation with evidence in RAW 264.7 and alveolar macrophage cells [144] , [149] . Mitochondrial swelling as well as disruption of cristae can cause membrane rupture and dysfunction [150] , [151] .…”

The stress-responsive cytotoxic effect of diesel exhaust particles on lymphatic endothelial cells

“…When exposed to DEPs, epithelial cell viability is compromised in the respiratory system 19 . In the case of alveolar macrophage, DEP exposure has induced the production of cytokines such as tumor necrosis factor-α (TNF-α), IL-1β, and IL-8 as well as cell apoptosis via mitochondrial dysfunction 20 , 21 . Additionally, portions of inhaled DEPs often translocate from the lungs to mediastinal lymph nodes and tend to activate dendritic cell (DC) function 22 .…”