Ozone (O3) and particulate matter (PM) are the most commonly encountered air pollutants in the United States. Exposure to even low levels of these pollutants has been associated with increased hospitalizations for respiratory disorders, exacerbations of asthma and other respiratory tract diseases. Coarse and fine mode PM is comprised of a number of classes of components, including biologicals, such as endotoxin (or lipopolysaccharide or LPS). Though regulated and considered on an individual basis, people often encounter increased exposure to O3 and LPS simultaneously with low level exposures causing exacerbation of lung disease. A number of observations suggest that LPS and O3 share a number of general mechanistic features, which mediate induction of neutrophilic inflammation. We have observed that expression of CD11b on circulating monocytes (and to lesser extent neutrophils) correlates very well with neutrophil influx to the airway following challenge with either agent. Others have observed that the toll-like receptor 4 (TLR4, which along with CD14 is a primary receptor for LPS) has been implicated in the airway response of rodents to ozone. The inflammatory nature of the response to both O3 and LPS, taken together with the observations outlined above, suggests that common determinants of susceptibility account for increased responsiveness to both stimuli. Animal studies suggest that ozone modifies the response to LPS. In humans, we have found that challenge with low levels of LPS can enhance macrophage responsiveness, and suspect that low level O3 may act similarly. Taken together, these observations lead to the following hypotheses: 1. That inflammatory response to ozone will correlate with response to LPS, suggesting a common airway inflammation response phenotype; 2. That low-level O3 exposure enhances macrophage responsiveness to inflammatory stimuli, and; 3. That low level ozone will enhance response to LPS. Testing these hypotheses will be used to better define the ways that O3 and LPS interact to exacerbate airway disease. ? ?
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