Antonio H. Miguel

Nrf2 Is a Key Transcription Factor That Regulates Antioxidant Defense in Macrophages and Epithelial Cells: Protecting against the Proinflammatory and Oxidizing Effects of Diesel Exhaust Chemicals

The proinflammatory effects of particulate pollutants, including diesel exhaust particles (DEP), are related to their content of redox cycling chemicals and their ability to generate oxidative stress in the respiratory tract. An antioxidant defense pathway, which involves phase II enzyme expression, protects against the pro-oxidative and proinflammatory effects of DEP. The expression of enzymes, including heme oxygenase-1 (HO-1) and GST, is dependent on the activity of a genetic antioxidant response element in their promoters. In this study we investigated the mechanism by which redox cycling organic chemicals, prepared from DEP, induce phase II enzyme expression as a protective response. We demonstrate that aromatic and polar DEP fractions, which are enriched in polycyclic aromatic hydrocarbons and quinones, respectively, induce the expression of HO-1, GST, and other phase II enzymes in macrophages and epithelial cells. We show that HO-1 expression is mediated through accumulation of the bZIP transcription factor, Nrf2, in the nucleus, and that Nrf2 gene targeting significantly weakens this response. Nrf2 accumulation and subsequent activation of the antioxidant response element is regulated by the proteasomal degradation of Nrf2. This pathway is sensitive to pro-oxidative and electrophilic DEP chemicals and is also activated by ambient ultrafine particles. We propose that Nrf2-mediated phase II enzyme expression protects against the proinflammatory effects of particulate pollutants in the setting of allergic inflammation and asthma.

Induction of Heme Oxygenase-1 Expression in Macrophages by Diesel Exhaust Particle Chemicals and Quinones via the Antioxidant-Responsive Element

Diesel exhaust particles (DEP) contain organic chemicals that contribute to the adverse health effects of inhaled particulate matter. Because DEP induce oxidative stress in the lung and in macrophages, effective antioxidant defenses are required. One type of defense is through the expression of the antioxidant enzyme, heme oxygenase I (HO-1). HO-1 as well as phase II detoxifying enzymes are induced via antioxidant response elements (ARE) in their promoters of that gene. We show that a crude DEP total extract, aromatic and polar DEP fractions, a benzo(a)pyrene quinone, and a phenolic antioxidant induce HO-1 expression in RAW264.7 cells in an ARE-dependent manner. N-acetyl cysteine and the flavonoid, luteolin, inhibited HO-1 protein expression. We also demonstrate that the same stimuli induce HO-1 mRNA expression in parallel with the activation of the SX2 enhancer of that gene. Mutation of the ARE core, but not the overlapping AP-1 binding sequence, disrupted SX2 activation. Finally, we show that biological agents, such as oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, could also induce HO-1 expression via an ARE-dependent mechanism. Prior induction of HO-1 expression, using cobalt-protoporphyrin, protected RAW264.7 cells against DEP-induced toxicity. Taken together, these data show that HO-1 plays an important role in cytoprotection against redox-active DEP chemicals, including quinones.

Determination of Four Quinones in Diesel Exhaust Particles, SRM 1649a, and Atmospheric PM2.5 Special Issue of Aerosol Science and Technology on Findings from the Fine Particulate Matter Supersites Program

Quinones are reactive organic compounds and are known to initiate reactions associated with many toxicological events. Their presence in air pollution has been demonstrated, but routine quantitative measurements are lacking. A quantitative method for the determination of four quinones was developed using diesel exhaust particles (DEP) and National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 1649a. The method was then used to analyze ambient air samples from different sites in Southern California. After extraction in dichloromethane, the target compounds were converted to their stable diacetyl derivatives and determined by electron impact GC-MS using selected ion monitoring. Calibration plots were obtained with deuterium-labeled internal standards. The four quinones, 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), 9,10-phenanthraquinone (9,10-PQ), and 9,10-anthraquinone (9,10-AQ), were quantified in DEP, in SRM 1649a, and in ambient air samples of PM2.5 collected in several rural and urban sampling locations upwind and downwind of major emission sources in Central Los Angeles. Mean concentration of individual target quinones ranged from 7.9–40.4 μg/g in the DEP, and from 5–730 pg/m3 in the PM2.5 samples. Precision (repeatability and reproducibility) varied from 2–22%. Further measurements of these species in future air samples should be considered in light of their potential health significance.

Formation and transport of 2‐nitrofluoranthene and 2‐nitropyrene of photochemical origin in the troposphere

The occurrence of 2-nitrofluoranthene and 2-nitropyrene in particulate matter collected in urban, suburban, forest, and remote areas located in Europe, America, Asia, and Antarctica was investigated. The results obtained confirm the photochemical origin of these components by gas phase reactions with OH radicals and their ubiquitous occurrence in the troposphere. An important role in their formation and dispersion seems to be played by carbon particles.

Seasonal and Spatial Variation of Polycyclic Aromatic Hydrocarbons in Vapor-Phase and PM2.5 in Southern California Urban and Rural Communities

Fifteen priority polycyclic aromatic hydrocarbons (PAHs) were measured in two rural communities (Atascadero and Lompoc) located several hundred km northwest of Los Angeles and in four urban communities 40–100 km downwind of Los Angeles (San Dimas, Upland, Mira Loma, and Riverside), during all seasons, from May 2001 to July 2002. PM2.5 and vapor-phase PAHs were collected, on prebaked quartz fiber filters and PUF-XAD-4 resin, respectively, at 113 LPM, during 24 h periods, every eighth day, and quantified by HPLC-Fluorescence. At all sites vapor-phase PAHs contained > 99.9% of the total PAH mass and were dominated by naphthalene (NAP), which varied from about 60 ng m − 3 in Lompoc, a community with light traffic, to ∼580 ng m − 3 in Riverside, a community traversed by ∼200,000 vehicles day− 1. During summer pollution episodes in urban sites, NAP concentrations reached 7–30 times annual averages. Except for summer episodes, concentrations of low MW PAHs showed small seasonal variations (∼2 times higher in winter). Similar concentrations of particle-phase PAHs were observed at all sites except for Lompoc. Benzo[ghi]perylene (BGP), a marker of gasoline exhaust emissions, showed the highest concentration among particle-phase PAHs, varying from 23.3 pg m−3 in Lompoc to 193 pg m−3 in Mira Loma. Benzo[a]pyrene and indeno[1,2,3-cd]pyrene, found exclusively in the particle phase, were much higher in urban sites (∼40–100 pg m−3), than in Lompoc (∼12 pg m−3). Winter particle-phase PAHs were 2 to 14 times higher than summer levels. Particle-phase PAHs were negatively correlated with mean air temperature in urban sites (r = −0.50 to −0.75), probably resulting from surface inversions occurring during winter. The data suggest that in Southern California vehicular exhaust emissions are a major contributor to particle-phase PAHs.

Biomass burning in the Amazon: characterization of the ionic component of aerosols generated from flaming and smoldering rainforest and savannah.

Samples (170) of biomass combustion smoke were obtained in Brazilian tropical rainforest and savannah during August-September 1992. Speciation of the ionic fraction of fine (d d > 2 µm) mode particles was achieved using ion chromatography, and the data were interpreted according to geographical region, vegetation type, and phase of combustion. The species measured were CH_3COO^-, HCOO^-, CI^-, NO_3^-, SO_4^(2-), C_2O_4^(2-), PO_4^(3-), Na^+, NH_4^+, K^+, Mg^(2+), and Ca^(2+). Mean total ionic contents for the fine mode were 5.6% (Brasilia) and 2.2% (Rondonia) and for the coarse mode were 8.3% (Brasilia) and 13.7% (Rondonia). The fine mode ionic fraction was dominated by potassium, chloride, and sulfate, while calcium and acetate were important in the coarse mode. Highest ionic contributions were always observed during flaming combustion. Sources of aerosols were condensation/coagulation, release of partially combusted plant material, and suspension of soil particles.

Characterization of indoor air quality in the cities of sao paulo and rio de janeiro, Brazil.

Levels of several gas- and particle-phase substances present in indoor air in nonindustrial office workplaces and in restaurants was acquired during the Southeastern Brazil lndoor Air Quality Study (SEBIAQS) carried out in the summer of 1993. Simultaneous indoor and outdoor samples collected in 12 sites in the cities of Sao Paulo and Rio de Janeiro and in a rural area were analyzed for inhalable particulate matter (IPM dp < 15 µm), inhalable volatilizable particulate organic carbon, black (soot) carbon, trace metals, UV-RSP (d_(50) < 3.5 µm) as a marker for environmental tobacco smoke (ETS), formaldehyde, acetaldehyde, carbon monoxide, and nicotine. Indoor levels were generally higher. Alcohol-fueled vehicle emissions contributed to indoor acetaldehyde. The major sources of trace elements indoors and outdoors were respectively soil dust and combustion, resuspension, and vehicles. Dry deposition indoors was observed for S (mainly sulfate), AI, Fe, and Mn.

Atmospheric Distribution of Gas- and Particle-Phase Quinones in Southern California

Quinones are reactive organic compounds known to initiate reactions associated with a host of toxicological events. Their presence in different atmospheres has been demonstrated although their sources remain uncertain. As a result of their reactivity and instability during chemical analysis, only a limited number of studies have reported on atmospheric concentrations of quinones in ambient air. Furthermore, besides the limited information on quinones associated with particulate matter, no previous studies have quantified vapor-phase quinones. We report vapor- and particle-phase concentrations of 1,2- and 1,4-naphthoquinones (1,2-NQ, 1,4-NQ), 9,10-phenanthraquinone (9,10-PQ), and 9,10-anthraquinone (9,10-AQ), measured over a 5-year period in Southern California. The results showed that vapor-phase concentrations of the target quinones were in general higher than those in the particle-phase. Vapor-phase concentrations ranged from 80 pg/m 3 for the AQ to 1747 pg/m 3 for the 1,4-NQ, and the particle-phase concentrations between 13 pg/m 3 for the 1,2-NQ and 250 pg/m 3 for 9,10-AQ. The target quinones were found to be distributed between vapor- and particle-phase, with the exception of 9,10-PQ found only in the particle-phase. The differences observed in the concentrations among sites and seasons suggest different source contributions; source sites were dominated by primary sources, while downwind locations showed a high contribution from photochemical activity.

Measurements of semivolatile and particulate polycyclic aromatic hydrocarbons in a bus station and an urban tunnel in Salvador, Brazil

Motor vehicles constitute a significant source of polycyclic aromatic hydrocarbon (PAH) emissions to the atmosphere. Particle-phase priority pollutant PAH concentrations and total suspended particle mass (TSP) were measured in the Lapa bus station and the Americo Simas Tunnel, located in the city of Salvador, Brazil. Separate samples were collected at the bus station at different times of the day, including rush- and non-rush-hour periods. The highest concentrations for nearly all 16 priority PAHs measured at the bus station were observed at 18:30 h, with chrysene showing the highest mean value (26.6 ng m-3). The highest average PAH concentrations measured in the tunnel were observed for pyrene (79.4 +/- 11.5 ng m-3) followed by fluoranthene (39.0 +/- 5.2 ng m-3) and chrysene (28.0 +/- 4.17 ng m-3). TSP levels reached 423 micrograms m-3 in the bus station, and values as high as 2 mg m-3 in the tunnel. The measured Salvador tunnel PAH profiles are very similar to the Salvador bus station profiles, and are similar to PAH profiles reported for the Kojouike Tunnel, located in Kurashiki City, Japan, and the Caldecott Tunnel, located in Berkeley, California.

Carbonaceous Aerosol Sources in Rio de Janeiro

Aerosol carbon concentrations, organic / elemental speciation, and carbon isotopic composition data (13C/12C ratios and 14C content) are reported from the second Rio de Janeiro Aerosol Characterization Study (RIO-JACS II), along with supplemental meteorologic and inorganic aerosol data. These data and their diurnal and weekday / weekend variability are used to identify sources of carbonaceous aerosols in the urban Rio air basin. Specifically, contributions from biogenic sources, anthropogenic emissions (principally transportation sources), and sugar cane-derived alcohol-fueled vehicular emissions to aerosol carbon levels in Rio are estimated from measurements of carbon-14, organic and elemental carbon, and 13C/12C isotopic composition in total aerosol samples collected at two ambient Rio sites and in a heavily traveled tunnel. The major source of elemental (soot) carbon appears to be diesel vehicles, but secondary sources of both biogenic and fossil organic aerosol carbon are indicated.