Chronic Exposure to Air Pollution Triggers Systemic Inflammation

Chronic inhalation of fine particulate matter (PM) has long been linked to increased morbidity and mortality from ischemic cardiovascular events, however until now the precise reasons for this have remained elusive. Sanjay Rajagopalan, professor of cardiovascular medicine at Ohio State, and colleagues exposed different groups of mice to filtered air or air containing between 8 and 10-times more PM than urban ambient air. The mice were exposed for 6-hours a day, 5-days a week, for at least 20-weeks. Some of the mice used in the experiment lacked a molecule called toll-like receptor 4 (TLR4), which recognizes specific characteristics of pathogens and then sends out signals to activate other immune system component. It is known that mice that lack TLR4 do not produce as much inflammation after exposure to pollution as do normal mice, thus suggesting that TLR4 plays an important role in the body's response to chronic exposure to PM. Results of the experiment showed that normal mice chronically exposed to air containing PM had higher levels of inflammatory monocytes in their spleens and bloodstream than mice breathing filtered air. Whereas mice with TLR4-deficiency exhibited a diminished response to breathing PM, thus suggesting that if the receptor is not present, the monocytes will not be released.  Results also showed that the increase in monocytes was accompanied by an increase in superoxides in the blood vessels. Again, the TLR4-deficient mice produced fewer oxygen free radicals in response to polluted air than did normal mice. The results of these and other experiments led Professor Rajagopalan to conclude: "PM stimulates inflammation in the lung, and products of that inflammation spill over into the body's circulation, traveling to fat tissue to promote inflammation and causing vascular dysfunction. We haven't identified the entire mechanism, but we have evidence now that activation of TLR4 influences this response."

Thomas Kampfrath, Andrei Maiseyeu, Zhekang Ying, Zubair Shah, Jeffrey A. Deiuliis, Xiaohua Xu, et al. Chronic Fine particulate matter exposure induces systemic vascular dysfunction via NADPH oxidase and TLR4 pathways. Circ Res. 2011;108:716-726.