Glenn Gookin

Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares.

We have previously demonstrated that intranasal administration of ambient ultrafine particles (UFP) acts as an adjuvant for primary allergic sensitization to ovalbumin (OVA) in Balb/c mice. It is important to find out whether inhaled UFP exert the same effect on the secondary immune response as a way of explaining asthma flares in already-sensitized individuals due to traffic exposure near a freeway. The objective of this study is to determine whether inhalation exposure to ambient UFP near an urban freeway could enhance the secondary immune response to OVA in already-sensitized mice. Prior OVA-sensitized animals were exposed to concentrated ambient UFP at the time of secondary OVA challenge in our mobile animal laboratory in Los Angeles. OVA-specific antibody production, airway morphometry, allergic airway inflammation, cytokine gene expression, and oxidative stress marker were assessed. As few as five ambient UFP exposures were sufficient to promote the OVA recall immune response, including generating allergic airway inflammation in smaller and more distal airways compared with the adjuvant effect of intranasally instilled UFP on the primary immune response. The secondary immune response was characterized by the T helper 2 and IL-17 cytokine gene expression in the lung. In summary, our results demonstrated that inhalation of prooxidative ambient UFP could effectively boost the secondary immune response to an experimental allergen, indicating that vehicular traffic exposure could exacerbate allergic inflammation in already-sensitized subjects.

Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum

To study central nervous system airborne PM related subchronic toxicity, SD male rats were exposed for eight weeks to either coarse (32 μg/m³), fine (178 μg/m³) or ultrafine (107 μg/m³) concentrated PM or filtered air. Different brain regions (olfactory bulb, frontal cortex, striatum and hippocampus), were harvested from the rats following exposure to airborne PM. Subsequently, prooxidant (HO-1 and SOD-2), and inflammatory markers (IL-1β and TNFα), apoptotic (caspase 3), and unfolded protein response (UPR) markers (XBP-1S and BiP), were also measured using real-time PCR. Activation of nuclear transcription factors Nrf-2 and NF-κB, associated with antioxidant and inflammation processes, respectively, were also analyzed by GSMA. Ultrafine PM increased HO-1 and SOD-2 mRNA levels in the striatum and hippocampus, in the presence of Nrf-2 activation. Also, ultrafine PM activated NF-κB and increased IL-1β and TNFα in the striatum. Activation of UPR was observed after exposure to coarse PM through the increment of XBP-1S and BiP in the striatum, accompanied by an increase in antioxidant response markers HO-1 and SOD-2. Our results indicate that exposure to different size fractions of PM may induce physiological changes (in a neuroanatomical manner) in the central nervous system (CNS), specifically within the striatum, where inflammation, oxidative stress and UPR signals were effectively activated.

Inhaled aerosol particle dosimetry in mice: a review.

The availability of molecular and genetic tools has made the mouse the most common animal model for a variety of human diseases in toxicology studies. However, little is known about the factors that will influence the dose delivery to murine lungs during an inhalation study. Among these factors are the respiratory tract anatomy, lung physiology, and clearance characteristics. Therefore, the objective of this paper is to briefly review the current knowledge on the aforementioned factors in mice and their implications to the dose delivered to mouse models during inhalation studies. Representative scientific publications were chosen from searches using the NCBI PubMed and ISI Web of Knowledge databases. Relevant respiratory physiological differences have been widely reported for different mouse strains and sexes. The limited data on anatomical morphometry that is available for the murine respiratory tract indicates significant differences between mouse strains. These differences have implications to the dose delivered and the biological outcomes of inhalation studies.