Air pollution molecules make key immune protein go haywire

DENVER — With the flip of a cellular switch, reactive molecules in air pollution can turn immune responses in the lungs topsy-turvy. When those reactive molecules fill baby mouse lungs, they can open the door to severe infections as well as set the stage for asthma later in life, researchers reported March 23 at the national meeting of the American Chemical Society.

The reactive molecules can damage cellular components such as DNA, proteins and lipids, causing oxidative stress and switching on an immune-regulating protein called aryl hydrocarbon receptor, or Ahr. In the lungs of infant mice, the reactive molecules dampened immune defenses, leaving the pups vulnerable to viral infections such as the flu. Such exposure also led mice pups to grow up to have hyperimmune responses, leading to severe asthma.

The findings could explain why human infants who breathe bad air are at high risk of severe lung infections and developing asthma.

Scientists knew that oxidative stress contributed to these health problems, but no one knew how, says environmental health researcher Nora Traviss of Keene State College in New Hampshire, who was not involved with the researchers’ study. “The depth that they’re going into is really exciting,” she says.

The reactive molecules, called free radicals, are created in the exhaust of burning fossil fuels and other materials. Free radicals arise from cooking stoves, car fumes, factories, wood fires and cigarettes.

The free radicals make up “a huge percentage of what might be in the air,” says pulmonary immunotoxicologist Stephania Cormier of the University of Tennessee Health Science Center in Memphis. For example, in Baton Rouge, La., an area with a lot of chemical plants and oil refineries, the amount of free radicals on airborne particles is higher than that of cigarette smoke, she says.

In mouse lungs, those free radicals can swipe electrons from cellular components, creating more reactive molecules and oxidative stress, Cormier and colleagues discovered. This turns on Ahr, which sets off rippling changes in the immune system.

To demonstrate this, the researchers exposed baby mice to a type of free radical found in air pollution, which triggered Ahr. The researchers then tested the pups’ immune response by giving them flu virus. Compared with flu-ridden pups not previously exposed to pollution, these pups had more virus particles in the lung and more severe illness; about 20 percent more of them died. Instead of fighting off the virus, the mice exposed to radicals cranked up an anti-inflammatory signal, Interleukin-10, and immune cells called regulatory T cells. These turned off infection defenses, leaving the pups especially vulnerable.

Pollution exposure early in life also led to long-term health issues. When exposed mice grew up, their previously suppressed immune response overreacted to allergens, leading to severe asthma.

When the researchers gave the baby mice an antioxidant enzyme before exposing them to pollution, the free radicals had no impact on the pups’ immune responses or their ability to fight the flu. This confirmed that free radicals and oxidative stress were responsible for derailing the immune system.

But that doesn’t necessarily mean that feeding human babies antioxidants would help, says toxicologist Tammy Dugas of Louisiana State University in Baton Rouge, who collaborates with Cormier and led the work on Ahr. Certain antioxidants taken to quell oxidative stress can backfire, creating even more oxidative stress, while other antioxidants stay outside cells, where they wouldn’t be able to block Ahr, she explains.