Winnie Kam

Glutamatergic Neurons in Rodent Models Respond to Nanoscale Particulate Urban Air Pollutants in Vivo and in Vitro

Background: Inhalation of airborne particulate matter (PM) derived from urban traffic is associated with pathology in the arteries, heart, and lung; effects on brain are also indicated but are less documented. Objective: We evaluated rodent brain responses to urban nanoscale (< 200 nm) PM (nPM). Methods: Ambient nPM collected near an urban freeway was transferred to aqueous suspension and reaerosolized for 10-week inhalation exposure of mice or directly applied to rat brain cell cultures. Results: Free radicals were detected by electron paramagnetic resonance in the nPM 30 days after initial collection. Chronic inhalation of reaerosolized nPM altered selected neuronal and glial activities in mice. The neuronal glutamate receptor subunit (GluA1) was decreased in hippocampus, whereas glia were activated and inflammatory cytokines were induced [interleukin-1α (IL-1α), tumor necrosis factor-α (TNFα)] in cerebral cortex. Two in vitro models showed effects of nPM suspensions within 24–48 hr of exposure that involved glutamatergic functions. In hippocampal slice cultures, nPM increased the neurotoxicity of NMDA (N-methyl-d-aspartic acid), a glutamatergic agonist, which was in turn blocked by the NMDA antagonist AP5 [(2R)-amino-5-phosphonopentanoate]. In embryonic neuron cultures, nPM impaired neurite outgrowth, also blocked by AP5. Induction of IL-1α and TNFα in mixed glia cultures required higher nPM concentrations than did neuronal effects. Because conditioned media from nPM-exposed glia also impaired outgrowth of embryonic neurites, nPM can act indirectly, as well as directly, on neurons in vitro. Conclusions: nPM can affect embryonic and adult neurons through glutamatergic mechanisms. The interactions of nPM with glutamatergic neuronal functions suggest that cerebral ischemia, which involves glutamatergic excitotoxicity, could be exacerbated by nPM.

Chemical characterization and redox potential of coarse and fine particulate matter (PM) in underground and ground-level rail systems of the Los Angeles Metro.

A campaign was conducted to assess personal exposure of coarse (2.5 μm < d(p) < 10 μm) and fine (d(p) < 2.5 μm) PM for two lines of the L.A. Metro-a subway (red) and light-rail (gold) line. Concurrent measurements were taken at University of Southern California (USC) to represent ambient conditions. A comprehensive chemical analysis was performed including total and water-soluble metals, inorganic ions, elemental and organic carbon, and organic compounds. Mass balance showed that in coarse PM, iron makes up 27%, 6%, and 2% of gravimetric mass for the red line, the gold line, and USC, respectively; in fine PM, iron makes up 32%, 3%, and 1%. Ambient air is the primary source of inorganic ions and organic compounds for both lines. Noncrustal metals, particularly Cr, Mn, Co, Ni, Mo, Cd, and Eu, were elevated for the red line and, to a lesser degree, the gold line. Mo exhibited the greatest crustal enrichment factors. The enriched species were less water-soluble on the red line than corresponding species on the gold line. Bivariate analysis showed that reactive oxygen species (ROS) activity is strongly correlated with water-soluble Fe (R(2) = 0.77), Ni (R(2 )= 0.95), and OC (R(2 )= 0.92). A multiple linear regression model (R(2) = 0.94, p < 0.001) using water-soluble Fe and OC as predictor variables was developed to explain the variance in ROS. In addition, PM from the red line generates 65% and 55% more ROS activity per m(3) of air than PM from USC and the gold line, respectively; however, one unit of PM mass from the gold line may be as intrinsically toxic as one unit of PM from the red line.

Characterization of organic, metal and trace element PM2.5 species and derivation of freeway-based emission rates in Los Angeles, CA.

On-road particulate matter (PM) was collected during a sampling campaign in March-April of 2011 on two major Los Angeles freeways, I-710 and Route 110. I-710 is a major route for heavy-duty vehicles (HDVs) traveling to and from the Ports of Long Beach and Los Angeles, while Route 110 has a much lower HDV fraction -3.9% versus 11.4%. Two sets of samples were collected for each roadway, each set representing approximately 50°h of on-road sampling. Concurrent sampling at a fixed site at the University of Southern Californias (USC) downtown Los Angeles campus provided estimates of urban background levels. Chemical analysis was performed for elemental carbon (EC), organic carbon (OC), polycyclic aromatic hydrocarbons (PAHs), hopanes and steranes, and metals and trace elements. Freeway-based emission rates (ERs) - mass per kilometer of freeway per hour - were calculated using mass concentrations, fuel characteristics, and traffic flow rates. These ERs are presented such that freeways could be treated as a line source of emissions for use in predictive models of population exposure for nearby communities. This data could also be used to assess the exposure of commuters to traffic-related PM2.5 emissions. ERs are compared to data from a previous fixed-site roadside study of I-710 as well as to reconstructed values from a tunnel study. ERs were generally lower (or comparable) on the gasoline-vehicle dominated freeway (Route 110) than the freeway with more diesel trucks (I-710), with EC and pyrene being notably lower on Route 110, findings consistent with the Route 110s lower HDV fraction. We found EC emission rates decreased over time suggesting that efforts to reduce diesel emissions from HDVs at the Ports of Los Angeles and Long Beach have been successful. While ERs for most of the organic species were within the range of values reported by previous studies, the present study found much higher ERs for metals and trace elements. This suggests that the sampling methods employed in this campaign are more efficient at capturing particles from sources such as resuspended road dust and wear from tires and brakes, which are usually not included in traditional sampling methodologies for assessing vehicular emissions (e.g. dynamometer studies).

Atmospheric ultrafine particles promote vascular calcification via the NF-κB signaling pathway

Exposure to atmospheric fine particulate matter (PM(2.5)) is a modifiable risk factor of cardiovascular disease. Ultrafine particles (UFP, diameter <0.1 μm), a subfraction of PM(2.5), promote vascular oxidative stress and inflammatory responses. Epidemiologic studies suggest that PM exposure promotes vascular calcification. Here, we assessed whether UFP exposure promotes vascular calcification via NF-κB signaling. UFP exposure at 50 μg/ml increased alkaline phosphatase (ALP) activity by 4.4 ± 0.2-fold on day 3 (n = 3, P < 0.001) and matrix calcification by 3.5 ± 1.7-fold on day 10 (n = 4, P < 0.05) in calcifying vascular cells (CVC), a subpopulation of vascular smooth muscle cells with osteoblastic potential. Treatment of CVC with conditioned media derived from UFP-treated macrophages (UFP-CM) also led to an increase in ALP activities and matrix calcification. Furthermore, both UFP and UFP-CM significantly increased NF-κB activity, and cotreatment with an NF-κB inhibitor, JSH23, attenuated both UFP- and UFP-CM-induced ALP activity and calcification. When low-density lipoprotein receptor-null mice were exposed to UFP at 359.5 μg/m(3) for 10 wk, NF-κB activation and vascular calcification were detected in the regions of aortic roots compared with control filtered air-exposed mice. These findings suggest that UFP promotes vascular calcification via activating NF-κB signaling.

A comparative assessment of PM2.5 exposures in light-rail, subway, freeway, and surface street environments in Los Angeles and estimated lung cancer risk

According to the U.S. Census Bureau, 570000+ commuters in Los Angeles travel for over 60 minutes to work. Studies have shown that a substantial portion of particulate matter (PM) exposure can occur during this commute. This study represents the integration of the results from five commute environments in Los Angeles. Personal PM exposures are discussed for the: (1) METRO gold line, a ground-level light-rail route, (2) METRO red line, a subway line, (3) the 110, a high volume freeway with low heavy-duty vehicle (HDV) fraction, (4) the 710, a major corridor for HDVs from the Port of Los Angeles, and (5) Wilshire/Sunset Boulevards, major surface streets. Chemical analysis including total and water-soluble metals and trace elements, elemental and organic carbon (EC/OC), and polycyclic aromatic hydrocarbons (PAHs) was performed. The focus of this study is to compare the composition and estimated lung cancer risk of PM2.5 (dp < 2.5 μm) for the five differential commute environments. Metals associated with stainless steel, notably Fe, Cr, and Mn, were elevated for the red line (subway), most likely from abrasion processes between the rail and brakes; elements associated with tire and brake wear and oil additives (Ca, Ti, Sn, Sb, and Pb) were elevated on roadways. Elemental concentrations on the gold line (light-rail) were the lowest. For water-solubility, metals observed on the red line (subway) were the least soluble. PAHs are primarily derived from vehicular emissions. Overall, the 710 exhibited high levels of PAHs (3.0 ng m−3), most likely due to its high volume of HDVs, while the red and gold lines exhibited low PAH concentrations (0.6 and 0.8 ng m−3 for red and gold lines, respectively). Lastly, lung cancer risk due to inhalation of PAHs was calculated based on a commuter lifetime (45 years for 2 hours per workday). Results showed that lung cancer risk for the 710 is 3.8 and 4.5 times higher than the light-rail (gold line) and subway (red line), respectively. With low levels of both metal and PAH pollutants, our results indicate that commuting on the light-rail (gold line) may have potential health benefits when compared to driving on freeways and busy roadways.

Development of a Two-Stage Virtual Impactor System for High Concentration Enrichment of Ultrafine, PM2.5, and Coarse Particulate Matter

A two-stage particle concentration enrichment system was developed to provide highly concentrated particles at low flow rates, for applications in areas such as toxicity studies of particulate matter (PM) as well as for increasing the signal-to-noise ratio in online particle sampling instruments. The current system is an extension of the Versatile Aerosol Concentration Enrichment System (VACES) developed at University of Southern California and operates by placing a second-stage miniature virtual impactor (VI) downstream of the VACES. Particles are sequentially enriched through each stage. Laboratory evaluations were conducted using various types of polydisperse particles to simulate typical ambient PM components as well as monodisperse polystyrene latex (PSL) particles. The systems configuration was tested by adjusting the intermediate flow rate, which is the intake flow of the second-stage VI (or minor flow of the first-stage VIs), for which 15 L/min was determined to be optimal in terms of maximizing the overall concentration enrichment. Particle size distributions before and after concentration enrichment were compared using a scanning mobility particle sizer. Overall, our results indicate that the sampled particles were relative consistently enriched by factors of 100–120 (i.e., a concentration enrichment efficiency 75–85% of the ideal value) based on both PM mass and number concentrations, and along with similar physical properties of the size distribution (i.e., mode, median). Continuous and time-integrated field tests using urban ambient PM also showed consistent enrichment factors (by roughly 100–120 times) for number and mass concentrations, black carbon, and PM-bound polycyclic aromatic hydrocarbons. Copyright 2013 American Association for Aerosol Research