Environmental Toxins May Cause Body's Defenses to Worsen Lung Disease

CINCINNATI—The University of Cincinnati (UC) has received $2.4 million to study whether environmental toxicants can stimulate the body’s natural defense system to cause additional damage in people with chronic lung diseases.

Michael Borchers, PhD, believes long-term exposure to certain environmental toxicants may activate a specific receptor—known as NKG2D—in lung cells that causes the immune system to attack stressed (damaged) lung tissue.

“When tissue is exposed to a pathogen (disease-causing agent), the immune system immediately wants to destroy the damaged cells so healthy tissue can take over,” explains Borchers, assistant research professor of environment health at UC and principal investigator for the study.

“But when the lungs experience chronic, low-level damage, we believe at some point that damage exceeds the body’s natural ability to repair tissue,” he adds. “And through the destruction of lung tissue, it may actually start contributing to chronic lung disease instead of protecting against it.”

UC scientists say when this happens repeatedly—such as through environmental tobacco or workplace exposures—it may cause the immune system to attack the damaged tissue in the same way it would if the tissue were infected with bacteria or a virus.

“The same signaling pathway necessary to protect the body from disease may actually have the opposite effect, causing harm in the lung when exacerbated by persistent exposure to environmental contaminants,” Borchers explains.

By blocking the NKG2D receptor, Borchers believes he can stop the immune system response and minimize damage to delicate tissue in the lung.

Lymphocytes, the white blood cells responsible for targeting and fighting off infection in the body, continually survey the epithelial cells lining the lungs to identify and destroy diseased cells. If the lymphocyte recognizes the tissue, Borchers explains, it simply continues its survey for problems. But if the cell receives a signal that the tissue is infected, it will automatically destroy it to protect the body from disease.

“The immune system thinks it’s eradicating disease from the body when it destroys cells that have been damaged by environmental toxins, but in chronic lung disease that destruction may be doing more harm than good,” he says.

Chronic pulmonary diseases cause irreversible damage and inflammation in the lungs that lead to scarring and narrowing of the airways. The most common of these diseases are obstructive pulmonary disease, chronic bronchitis and emphysema. When a large amount of tissue is destroyed, Borchers says, it can cause irreparable damage to the elasticity of the lung and lead to additional health problems.

Using an animal model, Borchers will expose surface cells in the lung to two environmental toxins—the bacteria pseudomonas aeruginosa, a major cause of in-hospital infections, and acrolein, an air pollutant found in tobacco smoke, smog and diesel exhaust—to determine how cells respond to infection and toxicant-induced cell damage.

“By looking at how the cells react to these stimuli, we hope to gain insight into what triggers and mediates the immune system response,” Borchers says.

This will help scientists determine which lymphocytes are important for regulating damage in the lungs, so they can develop ways to “tweak” the immune system and prevent the lymphocytes from causing additional damage to already-injured tissue.

Borchers says understanding these pathways could play an important role in future drug treatments for patients with chronic obstructive pulmonary disease and the basic scientific findings may also have applications in asthma, cystic fibrosis and other chronic lung diseases.

The overall goal of the study is to expand existing scientific knowledge of how epithelial cells in the lungs communicate with the immune system in response to environmental and occupational pollutants.

“The challenge with pulmonary diseases is that there are no cures,” says Borchers. “We can manage the symptoms of the disease, but we can’t cure it because destruction of the airways is irreversible.

“We need a better understanding of the causes and pathways that lead to pulmonary disease if we are to improve the outcome for patients with chronic disease,” he adds.

The five-year, basic-science study is funded by a National Institute of Environmental Health Sciences (NIEHS) Outstanding New Environmental Scientist Award.

According to the American Lung Association, more than 35 million Americans suffer from chronic lung diseases, including chronic obstructive pulmonary disease, emphysema, bronchitis and asthma. Chronic lung diseases result in 349,000 deaths each year and, left untreated, can lead to heart disease and other serious health conditions.