Combined adjuvant effects of ambient vapor-phase organic components and particulate matter potently promote allergic sensitization and Th2-skewing cytokine and chemokine milieux in mice: The importance of mechanistic multi-pollutant research.

Although exposure to ambient particulate matter (PM) is linked to asthma, the health effects of co-existing vapor-phase organic pollutants (vapor) and their combined effects with PM on this disease are poorly understood. We used a murine asthma model to test the hypothesis that exposure to vapor would enhance allergic sensitization and this effect would be further strengthened by co-existing PM. We found that vapor and PM each individually exerted adjuvant effects on OVA sensitization.

Air quality impacts of a CicLAvia event in Downtown Los Angeles, CA.

CicLAvia in Los Angeles, CA is the open streets program that closes streets to motorized vehicles and invites people to walk, run, play or ride their bicycles on these streets, allowing them to experience the city in a new way and get exercise at the same time. Since the events reduce the motorized traffic flow, which is a significant source of air pollution, on the streets, it is reasonable to hypothesize that the CicLAvia events can reduce the concentrations of traffic-emitted air pollutants during the road closure. This study is the first experiment to test this hypothesis.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic.

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels.

Chemical reactivities of ambient air samples in three Southern California communities.

Unlabelled: The potential adverse health effects of PM2.5 (particulate matter with an aerodynamic diameter<2.5 μm) and vapor samples from three communities that neighbor railyards, Commerce (CM), Long Beach (LB), and San Bernardino (SB), were assessed by determination of chemical reactivities attributed to the induction of oxidative stress by air pollutants.

Ambient vapor samples activate the Nrf2-ARE pathway in human bronchial epithelial BEAS-2B cells.

Ambient air pollutants have been reported to induce oxidative stress based inflammatory responses in humans and experimental animals. However, most of these reports describe the actions of the particulate phase of ambient and exhaust samples. We describe here results of studies investigating the actions of the vapor phase of ambient air samples collected in the midtown area of Los Angeles on human bronchial epithelial BEAS-2B cells using DNA microarray analysis.

Redox and electrophilic properties of vapor- and particle-phase components of ambient aerosols.

Particulate matter (PM) has been the primary focus of studies aiming to understand the relationship between the chemical properties of ambient aerosols and adverse health effects. Size and chemical composition of PM have been linked to their oxidative capacity which has been postulated to promote or exacerbate pulmonary and cardiovascular diseases. But in the last few years, new studies have suggested that volatile and semi-volatile components may also contribute to many adverse health effects.

Particulate matter (PM) research centers (1999-2005) and the role of interdisciplinary center-based research.

Objective: The U.S. Environmental Protection Agency funded five academic centers in 1999 to address the uncertainties in exposure, toxicity, and health effects of airborne particulate matter (PM) identified in the "Research Priorities for Airborne Particulate Matter" of the National Research Council (NRC).

Determination of metal-based hydroxyl radical generating capacity of ambient and diesel exhaust particles.

Numerous studies have suggested the association of reactive oxygen species (ROS) with adverse health effects derived from exposure to airborne particulate matter (PM) and diesel exhaust particles (DEP). This redox activity has been attributed to both inorganic and organic species present in these particles, but a clear distinction has not been established between the contribution of each. This article describes an application of an analytical procedure, based on the reaction of salicylic acid with hydroxyl radical to form dihydroxybenzoate (DHBA) isomers, to measure transition metal-based redox activity associated with ambient and diesel exhaust particles.

Key scientific findings and policy- and health-relevant insights from the U.S. Environmental Protection Agency's Particulate Matter Supersites Program and related studies: an integration and synthesis of results.

In 1998, the U.S. Environmental Protection Agency (EPA) initiated a major air quality program known as the Particulate Matter (PM) Supersites Program.

Electrophilic and redox properties of diesel exhaust particles.

The adverse health effects of air pollutants have been associated with their redox and electrophilic properties. Although the specific chemical species involved in these effects are not known, the characterization of their general physical and chemical properties is important to our understanding of the mechanisms by which they cause health problems. This manuscript describes results of a study examining the partition properties of these activities in aqueous and organic media.

Redox cycling of 9,10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 cells.

9,10-Phenanthraquinone (PQ), a component of airborne particulate matter, causes marked cellular protein oxidation and cytotoxicity through a two-electron reduction to 9,10-dihydroxyphenanthrene (PQH2), which is associated with the propagation of reactive oxygen species (K. Taguchi et al., Free Radic.

Evaluating the toxicity of airborne particulate matter and nanoparticles by measuring oxidative stress potential--a workshop report and consensus statement.

Background: There is a strong need for laboratory in vitro test systems for the toxicity of airborne particulate matter and nanoparticles. The measurement of oxidative stress potential offers a promising way forward.

Objectives: A workshop was convened involving leading workers from the field in order to review the available test methods and to generate a Consensus Statement.

Inhalation of concentrated ambient particulate matter near a heavily trafficked road stimulates antigen-induced airway responses in mice.

Motor vehicle exhaust emissions are known to exacerbate asthma and other respiratory diseases. Several studies have demonstrated significant associations between living near highly trafficked roadways and increased incidence of asthma and increased severity of asthma-related symptoms, medication usage, and physician visits. This study tested the hypotheses that (1) exposure to particulate matter (PM) near a heavily trafficked Los Angeles freeway would enhance inflammatory and allergic responses in ovalbumin (OVA)-sensitized BALB/c mice compared to sensitized, clean air controls, and (2) there would be differences in response at two distances downwind of heavily traveled freeways because of greater toxicity of PM closest to the freeway.

Chemical knockdown of protein-tyrosine phosphatase 1B by 1,2-naphthoquinone through covalent modification causes persistent transactivation of epidermal growth factor receptor.

1,2-Naphthoquinone (1,2-NQ), an atmospheric contaminant, causes the contraction of guinea pig trachea through the activation of epidermal growth factor receptor (EGFR) by inhibiting protein-tyrosine phosphatases (PTPs). Phosphorylation of EGFR is negatively regulated by PTPs, but details of the mechanism by which 1,2-NQ inhibits PTPs have not been elucidated. Results described in this report demonstrate that 1,2-NQ forms covalent bonds with PTP1B after exposure to human epithelial A431 cells.

An approach to evaluate two-electron reduction of 9,10-phenanthraquinone and redox activity of the hydroquinone associated with oxidative stress.

Quinones are widely used as medicines or redox agents. The chemical properties are based on the reactions against an electron donor. 9,10-Phenanthraquinone (PQ), which is a quinone contaminated in airborne particulate matters, forms redox cycling, not Michael addition, with electron donors.

Relationship between redox activity and chemical speciation of size-fractionated particulate matter.

Background: Although the mechanisms of airborne particulate matter (PM) related health effects remain incompletely understood, one emerging hypothesis is that these adverse effects derive from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within affected cells. Typically, ROS are formed in cells through the reduction of oxygen by biological reducing agents, with the catalytic assistance of electron transfer enzymes and redox active chemical species such as redox active organic chemicals and metals. The purpose of this study was to relate the electron transfer ability, or redox activity, of the PM samples to their content in polycyclic aromatic hydrocarbons and various inorganic species.

Inhalation of concentrated ambient particulate matter near a heavily trafficked road stimulates antigen-induced airway responses in mice.

The goal of this study was to test the following hypotheses: (1) exposure to mobile emissions from mobile sources close to a heavily trafficked roadway will exacerbate airway inflammation and allergic airway responses in a sensitized mouse model, and (2) the magnitude of allergic airway disease responses will decrease with increasing distance from the roadway. A particle concentrator and a mobile exposure facility were used to expose ovalbumin (OVA)-sensitized BALB/c mice to purified air and concentrated fine and concentrated ultrafine ambient particles at 50 m and 150 m downwind from a roadway that was heavily impacted by emissions from heavy duty diesel-powered vehicles. After exposure, we assessed interleukin (IL)-5, IL-13, OVA-specific immunoglobulin E, OVA-specific immunoglobulin G1, and eosinophil influx as biomarkers of allergic responses and numbers of polymorphonuclear leukocytes as a marker of inflammation.

Redox activity of airborne particulate matter at different sites in the Los Angeles Basin.

Epidemiologic studies have shown associations between ambient particulate matter (PM) and adverse health outcomes including increased mortality, emergency room visits, and time lost from school and work. The mechanisms of PM-related health effects are still incompletely understood, but a hypothesis under investigation is that many of the adverse health effects may derive from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within affected cells. While the adverse effects from PM have historically been associated with the airborne concentration of PM and more recently fine-particle PM, we considered it relevant to develop an assay to quantitatively measure the ability of PM to catalyze ROS generation as the initial step in the induction of oxidative stress.

1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea.

1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PM2.5. We have found that this quinone is capable of causing a concentration-dependent contraction of tracheal smooth muscle in guinea pigs with EC50 value of 18.

The interactions of 9,10-phenanthrenequinone with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a potential site for toxic actions.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the oxidative phosphorylation of glyceraldehyde 3-phosphate to 1,3-diphosphoglycerate, one of the precursors for glycolytic ATP biosynthesis. The enzyme contains an active site cysteine thiolate, which is critical for its catalytic function. As part of a continuing study of the interactions of quinones with biological systems, we have examined the susceptibility of GAPDH to inactivation by 9,10-phenanthrenequinone (9,10-PQ).

Effects of a single intratracheal administration of phenanthraquinone on murine lung.

Although several studies have reported that diesel exhaust particles (DEP) affect cardiorespiratory health in animals and humans, the responsible components in DEP for the effects remain to be defined. Diesel exhaust particles contain quinones that can catalyse the generation of reactive oxygen species, resulting in the induction of oxidative stress. Oxidative stress can correlate with a variety of diseases and health effects.

Size distribution of chromate paint aerosol generated in a bench-scale spray booth.

Spray painters are potentially exposed to aerosols containing hexavalent chromium [Cr(VI)] via inhalation of chromate-based paint sprays. Evaluating the particle size distribution of a paint spray aerosol, and the variables that may affect this distribution, is necessary to determine the site and degree of respiratory deposition and the damage that may result from inhaled Cr(VI)-containing paint particles. This study examined the effect of spray gun atomization pressure, aerosol generation source and aerosol aging on the size distribution of chromate-based paint overspray aerosols generated in a bench-scale paint spray booth.

Size distribution and speciation of chromium in paint spray aerosol at an aerospace facility.

Spray painters are potentially exposed to aerosol containing Cr(VI) via inhalation of chromate-based paint spray. Two field studies were conducted at an aerospace facility to determine the size distribution and speciation of Cr(VI) in paint spray aerosol. Sampled paint products consisted of sparingly soluble strontium chromate in an epoxy resin matrix, a matrix generally known for its durability and toughness.

An examination of quinone toxicity using the yeast Saccharomyces cerevisiae model system.

The toxicity of quinones is generally thought to occur by two mechanisms: the formation of covalent bonds with biological molecules by Michael addition chemistry and the catalytic reduction of oxygen to superoxide and other reactive oxygen species (ROS) (redox cycling). In an effort to distinguish between these general mechanisms of toxicity, we have examined the toxicity of five quinones to yeast cells as measured by their ability to reduce growth rate. Yeast cells can grow in the presence and absence of oxygen and this feature was used to evaluate the role of redox cycling in the toxicity of each quinone.