The Dual Effect of the Particulate and Organic Components of Diesel Exhaust Particles on the Alteration of Pulmonary Immune/Inflammatory Responses and Metabolic Enzymes

Abstract

Exposure to diesel exhaust particles (DEP) is an environmental and occupational health concern. This review examines the cellular actions of the organic and the particulate components of DEP in the development of various lung diseases. Both the organic and the particulate components cause oxidant lung injury. The particulate component is known to induce alveolar epithelial damage, alter thiol levels in alveolar macrophages (AM) and lymphocytes, and activate AM in the production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The organic component, on the other hand, is shown to generate intracellular ROS, leading to a variety of cellular responses including apoptosis. There are a number of differences between the biological actions exerted by these two components. The organic component is responsible for DEP induction of cytochrome P450 family 1 enzymes that are critical to the polycyclic aromatic hydrocarbons (PAH) and nitro-PAH metabolism in the lung as well as in the liver. The particulate component, on the other hand, causes a sustained down-regulation of CYP2B1 in the rat lung. The significance of this effect on pulmonary metabolism of xenobiotics and endobiotics remains to be seen, but may prove to be an important factor governing the interplay of the pulmonary metabolic and inflammatory systems. Long-term exposures to various particles including DEP, carbon black (CB), TiO2, and washed DEP devoid of the organic content, have been shown to produce similar tumorigenic responses in rodents. There is a lack of correlation between tumor development and DEP chemical-derived DNA adduct formation. But the organic component has been shown to generate ROS that produce 8-hydroxydeoxyguanosine (8-OHdG) in cell culture. The organic, but not the particulate, component of DEP suppresses the production of pro-inflammatory cytokines by AM and the development of Th1 cell-mediated immunity. The mechanism for this effect is not yet clear, but may involve the induction of heme oxygenase-1 (HO-1), a cellular genetic response to oxidative stress. Both the organic and the particulate components of DEP enhance respiratory allergic sensitization. Part of the DEP effects may be due to a depletion of glutathione in lymphocytes. The organic component, which is shown to induce IL-4 and IL-10 productions, may skew the immunity toward Th2 response, whereas the particulate component may stimulate both the Th1 and Th2 responses. In conclusion, the literature shows that the particulate and organic components of DEP exhibit different biological actions but both involve the induction of cellular oxidative stress. Together, these effects inhibit cell-mediated immunity toward infectious agents, exacerbate respiratory allergy, cause DNA damage, and under long-term exposure, induce the development of lung tumors.

Oxidative Stress, Inflammatory Biomarkers, and Toxicity in Mouse Lung and Liver after Inhalation Exposure to 100% Biodiesel or Petroleum Diesel Emissions

“…While D100 exposure resulted in inducing both Th1 (e.g., IFNγ,TNF-α) and Th2 (e.g., IL-6, IL-10) types of immune responses to a similar extent, B100 CE favored the Th2 type of response ( Figure 3B). This is further corroborated by studies where elevated levels of oxidative stress, as seen upon B100 exposure, were associated with the release of IL-4/IL-10 cytokines (Ma et al, 2002), which suppress Th1 response (IFNγ, TNF-α) and trigger Th2 responses (IL-6, IL-10). Thus, the increased post combustion organic component of BD (Graboski et al, 2003), as well as the elevated oxidative stress responses upon B100 CE exposure, may serve as the basis for these differential immune effects exhibited by BD and D (Figure 3).…”

Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location

“…45 and 46), and can damage DNA. Other factors that may contribute to oxidative stress include changes in metabolism or inflammation in mice exposed to particulate air pollution (44). It is unclear whether ROS generated elsewhere in the body leads to oxidative stress and DNA strand breaks in gametes.…”

“…Strand breaks may reflect exposure to agents that generate reactive oxygen species (ROS), which can be produced by exposure to particulate matter, PAHs (reviewed in ref. 44), or metals (reviewed in refs. 45 and 46), and can damage DNA.…”

Health Survey on Workers and Residents Near the Municipal Waste and Industrial Waste Incinerators in Korea.

“…The association of MDA as biomarker of lipid peroxidation and PCDD/Fs were significant, because PCDD/Fs are lipid soluble. Oxidative damage may inhibit cell-mediated immunity toward infectious agents, exacerbate respiratory allergy, cause DNA damage, and under longterm exposure, induce the development of tumors [41][42][43][44][45] .…”