Chronic inhalation of polluted air ‘can lead to inflammation, heart risk’

April 17th, 2011 - 6:41 pm ICT by ANI  

Washington, April 17 (ANI): A study led by an Indian origin scientist, has suggested that chronic inhalation of polluted air triggers the release of white blood cells that leads to inflammation and risk of heart disease.

Ohio State University scientists have described studies in mice suggesting that chronic exposure to very fine particulate matter triggers events that allow white blood cells to escape from bone marrow and work their way into the bloodstream.

Their presence in and around blood vessels alters the integrity of vessel walls and they also collect in fat tissue, where they release chemicals that cause inflammation.

“Our main hypothesis is that particulate matter 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,” said Sanjay Rajagopalan, professor of cardiovascular medicine at Ohio State and senior author of the study.

“We haven’t identified the entire mechanism, but we have evidence now that activation of toll-like receptor 4, or TLR4, influences this response.”

For this study, the scientists exposed different groups of mice to either filtered air or air containing between eight and 10 times more fine particulates than the ambient air in an urban environment - an average of approximately 111 micrograms per cubic meter. The mice were exposed for six hours per day for five days per week for at least 20 weeks.

The polluted air contained fine particulates that are so tiny - 2.5 micrometers or smaller in diameter, or about 1/30th of the average width of a human hair - that they can reach deep areas of the lungs and other organs in the body.

For most of the experiments, the effects of exposure to pollution were compared in normal mice and mice deficient in TLR4.

After exposure to polluted air, the normal mice showed higher levels of white blood cells known as inflammatory monocytes in their spleens and circulating in their bloodstream than did mice breathing filtered air.

Deficiency of TLR4 diminished this effect in mice breathing dirty air. That suggested that if the receptor is not active, the monocytes would not be released.

Other findings implicated yet another potential compound involved in the damage. The increase in monocytes was accompanied by an increase in superoxides in the blood vessels. These compounds are designed to kill pathogens, but they are toxic if they have no bug to fight. They are produced by an enzyme called NADPH oxidase - and NADPH oxidase is found inside monocytes.

In an experiment comparing normal mice and mice lacking a component of the NADPH oxidase enzyme, the mice without the enzyme produced fewer oxygen free radicals in response to polluted air than did normal mice.

Yet another model of mice genetically altered so their monocytes express yellow fluorescent protein allowed the researchers to observe exactly where the monocytes traveled in segments of mouse muscles and fat tissue. In mice breathing polluted air, the monocytes began to stick to blood vessel walls and fat cells.

“This is a sign that the monocytes are responding to inflammatory stimuli - which in our case is particulate matter - and then in turn they can cause more inflammation because they release inflammatory factors,” said Rajagopalan.

Those factors include what are called proinflammatory cytokines, including TNFa (tumor necrosis factor alpha), MCP-1 (monocyte chemoattractant protein) and IL-12 (interleukin-12). These are chemical messengers that cause inflammation, most often to fight infection or repair injury. When they circulate without an infection to fight, the body experiences excess inflammation.

Mice breathing polluted air showed higher levels of these cytokines in their blood than did mice breathing filtered air. And the mice deficient in the TLR4 receptor showed dramatically lower levels of the cytokines.

The research is published in a recent issue of the journal Circulation Research. (ANI)

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