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EFFECT OF SIZE AND CHEMISTRY OF AMBIENT, COMBUSTION AND SURROGATE PARTICULATE MATTER (PM) ON PULMONARY INFLAMMATORY RESPONSES IN RODENTS
Impact/Purpose:
This research program specifically addresses efforts to (1) Describe the role of PM size in causing health effects in pulmonary cells; (2) Distinguish the respective toxic potentials of model and ambient PM size fractions in healthy animals and using an in vitro bioassay system; (3) Define PM toxicity by source derivation using in vivo and in vitro bioassay systems; and (4) Validate animal and in vitro bioassay systems for assessing the relative potency of PM and/or its extractable components.
Description:
While there is much evidence that airborne particulate matter (PM) can create adverse health effects including increased morbidity and mortality, the actual physico-chemical characteristics of particles which cause these effects remains elusive. One central hypothesis is that PM is to some degree pro-inflammatory, either by virtue of toxic bioavailable components or by participating in oxidative injury type reactions. As well as chemical differences, it has also been shown that the ultrafine fractions (<0.1 micron) of model particles such as carbon black and titanium dioxide are more pro-inflammatory than larger particles (1 micron) with the same chemistry. This enhanced effect is thought to be due to increased surface area. The purpose of this project is to compare the pro-inflammatory effects of a range of ambient and combustion particles which differ in both size and chemistry, in order to provide relative ranking of toxicity in a mouse bioassay system. In addition, these particles can be applied to endotoxin sensitive and resistant mice to determine the role of LPS in causing effects in ambient particles and for investigating the role of Tlr4 receptors in signaling PM-induced inflammatory responses. To date, studies have characterized pulmonary inflammatory responses to RTP PM fractions collected by the MASS air sampler, on ambient ultrafine, fine and coarse particles collected on a high volume sampler in Chapel Hill, and on ultrafine, fine and coarse fractions of combusted coal. The data show differential effects according to both the size and chemical make-up of the particles and a role for endotoxin and /or Tlr 4 receptors in signaling the responses.