Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways

Abstract

In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS effects in apolipoprotein E knockout (ApoE-/-) mice exposed to two levels of concentrated ultrafine particulate matter in central Los Angeles. Mice were killed 24 hr after the last exposure and brain, liver, heart, lung and spleen tissues were collected and frozen for subsequent bioassays. There was clear evidence of aberrant immune activation in the brains of exposed animals as judged by a dose-related increase in nuclear translocation of two key transcription factors, NF-kB and AP-1. These factors, are involved in the promotion of inflammation. Increased levels of glial fibrillary acidic protein (GFAP) were also found consequent to particulate inhalation suggesting that glial activation was taking place. In order to determine the mechanism by which these events occurred, levels of several MAP kinases involved in activation of these transcription factors were assayed by Western blotting. There were no significant changes in the proportion of active (phosphorylated) forms of ERK-1, IkB and p38. However the fraction of JNK in the active form was significantly increased in animals receiving the lower concentration of concentrated ambient particle (CAPs). This suggests that the signaling pathway by which these transcription factors are activated involves the activation of JNK.

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…Specific toxicological actions include impairment of phagocytosis and breakdown of defence mechanisms, crossing tissues and cell membranes, injury to cells, generation of reactive oxygen species, oxidative stress, inflammation, production of cytokines, depletion of glutathione, mitochondrial exhaustion, and damage to protein and DNA, most of which also occurs with larger size PM (Bakand, Hayes & Dechsakulthorn, 2012). Biodistribution studies also suggest that the effects of ultrafine particles may very well be observed in organs other than those that correspond to the port of entry -for example, the central nervous system (Kleinman et al, 2008;Kreyling et al, 2013). In light of different biodistributions on inhalation and the likelihood that ultrafine particles can escape natural defence mechanisms, such as phagocytosis, it is likely that ultrafine particles will also be linked to biological pathways and responses that differ from larger size particles (fine and coarse PM).…”

Optimizing superparamagnetic iron oxide nanoparticles as drug carriers using an in vitro blood–brain barrier model

“…Hence, generating innovative strategies for facilitating the targeting of nanoparticle agents across the BBB, while developing a reduced toxicity profile for these agents, remains a challenge in the field. [18][19][20] As a result, the objective of the present in vitro study was to investigate the proper modification for SPIONs for nontoxic brain drug delivery by using an optimized BBB model.…”

Particle Concentration on Freeways: Affecting Factors and a Simple Model Development

“…Exposure to particulate matter (PM) and in particular, ultrafine particles (UFPs, diameter < 100 nm), have been associated with increasing mortality and morbidity rates by many epidemiological studies (Johnston et al, 2000;Donaldson et al, 2002;MacNee and Donaldson, 2003;Gilmour et al, 2004;Kleinman et al, 2008;Nemmar and Inuwa, 2008;Zuurbier et al, 2011). In an urban area, traffic emissions are the dominant source of UFPs and other air pollutants (Cyrys et al, 2008).…”