Body's Own Immune System Might Worsen Lung Disease
Published October 2006
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 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 environmental 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.
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 receives a signal that the tissue is infected, Borchers explains, 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 inhospital 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.
“The challenge with pulmonary diseases is that there are no cures,” says Borchers. “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.”
Borchers’s five-year, basicscience study is funded by a National Institute of Environmental Health Sciences Outstanding New Environmental Scientist Award.