Project at a Glance
Project Status: complete
Title: Location specific systemic health effects of ambient particulate matter
Principal Investigator / Author(s): Wilson, Dennis
Contractor: UC Davis
Contract Number: 10-302
Research Program Area: Health & Exposure
Topic Areas: Health Effects of Air Pollution
Previous work by the contractor and others demonstrates induction of a systemic pro-inflammatory and pro-coagulant state in response to inhalation of environmental particulate matter. This work demonstrated PM exposure activated platelets to a enhanced state of reactivity and suggested this could be a key factor in adverse cardiovascular events. This project evaluated pulmonary inflammation and systemic inflammatory and platelet responses to fine and ultrafine (PM2.5) ambient particulate matter collected from an urban (Sacramento) and rural (Davis) location. The objective of these experiments was to determine whether prior chelation of transition metals with deferoxamine mesylate (DFM) or binding of bacterial source endotoxin by polymyxin B reduced pulmonary and systemic responses to PM2.5. The contractor hypothesized those inflammatory responses to a more transition metal rich urban source PM2.5 would be inhibited more by metal chelation while rural source PM2.5 would be more affected by endotoxin binding. Adult mice were given intratracheal instillations of collected PM2.5 and pulmonary pathology, systemic cytokine concentrations, and platelet activation were evaluated 24 hours later. To better assess contributions of aromatic hydrocarbons, oxidants or pro-inflammatory responses to biologically active material like endotoxin, the contractor used laser capture microscopy to probe specific anatomic locations in lung for gene responses associated with each of these components. The results support the following conclusions:
1) Urban source PM2.5 was significantly more pro-inflammatory than an equivalent dose by mass of rural source PM2.5.
2) DFM pre-treatment of urban source PM2.5 did not decrease PM induced pulmonary inflammation.
3) Treatment with DFM alone led to significant systemic platelet activation.
4) Pulmonary inflammatory responses to both urban and rural source PM2.5 were inhibited by pre-incubation of PM2.5 with polymyxin B.
5) In contrast to several prior animal experiments that demonstrated significant activation of circulating platelets after exposures to concentrated ambient particulates for two-weeks in the field,, this study with a single exposure dose found no evidence of platelet activation in response to instilled PM2.5 at 24 hours after exposure.
6) Urban source PM2.5 elicited transcription of genes associated with polycyclic aromatic hydrocarbon (PAH) metabolism (CYP 1A1, Aldehyde dehydrogenase), reactive oxygen species (ROS) response elements (ATF3, HOX-1) and inflammation (CCL-20, IL-1β, GM-CSF) in small airways, pulmonary arterioles and alveolar parenchyma.
For questions regarding this research project, including available data and progress status, contact: Heather Choi at (916) 322-3893
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