Body's defenses may worsen chronic lung diseases in smokers

February 9, 2009,

Although the immune system is designed to protect the body from harm, it may actually worsen one of the most difficult-to-treat respiratory diseases: chronic obstructive pulmonary disorder (COPD), according to new University of Cincinnati (UC) research.

In a preclinical research study, UC environmental health scientists have identified a link between cigarette smoke and activation of a specific cellular receptor (NKG2D) critical to immune system activation. They say the finding is key to understanding COPD disease progression and developing future interventional drug therapies.

"People have historically believed that if you smoke, you suppress the immune system. We've shown that you actually activate certain parts of the immune system and it could potentially work against you," explains Michael Borchers, PhD, lead investigator of the study and UC assistant professor of environmental health.

Borchers and his team report their findings in the March 2009 issue of the Journal of Clinical Investigation. The study appears online ahead of print Feb. 9, 2009. It is the first study to report data defining a link between the immune system and COPD disease progression and severity.

COPD is a progressive pulmonary disease believed to be caused by long-term cigarette smoking. The irreversible and incurable condition is characterized by emphysema and severe inflammation of the lung tissue.

Previous research had suggested that immune cells (lymphocytes) contributed to chronic inflammation, a key indicator of COPD; however, it was unclear whether this caused extensive cellular damage.

For this study, Borchers' team developed a transgenic mouse model to further examine how the immune system responds to chronic inflammation indicative of COPD. His team hypothesized that when tissue was damaged, the cells would send signals to the immune system indicating they are transformed—similar to cancer or virally infected cells—and must be destroyed.

Scientists examined molecular signaling pathways in lung tissue exposed to cigarette smoke and found a strong correlation between cellular stress signals, activation of the immune system and development of COPD-like disease.

This method was repeated and cross-referenced in tissue samples from a human cohort that included non-smokers, smokers with COPD and smokers who did not develop COPD. In patients who had never smoked, there was a complete absence of the NKG2D signal. Current and former smokers who developed the disease expressed signals that correlated with severe COPD disease.

By combining both sets of data, they determined that cigarette smoke set off a molecular chain of events resulting in activation of a specific receptor—NKG2D—in lung cells, causing the immune system to attack stressed (damaged) lung tissue.

"Our study is evidence that when the lungs are exposed to chronic damage from cigarette smoke, at some point that damage exceeds the body's natural ability to repair tissue and can start to contribute to COPD instead of protecting against it," Borchers says.

Borchers intends to expand this research using other genetically altered mouse models to explore the relationship between the NKG2D receptor and other immune pathways involved in of alterations in the immune system of COPD patients.

Source: University of Cincinnati

Explore further: A synthetic approach to helping the immune system thwart infections

Related Stories

A synthetic approach to helping the immune system thwart infections

February 22, 2018
Yale researchers have developed a set of synthetic molecules that may help boost the strength of a key, virus-fighting protein.

Immune cells hold their memory of how to respond to allergens in a surprising way

February 22, 2018
Understanding how the immune system remembers allergy-causing antigens could help prevent severe reactions.

Team develops new technology platform for cancer immunotherapy

February 22, 2018
Johns Hopkins researchers have invented a new class of immunotherapeutic agents that are more effective at harnessing the power of the immune system to fight cancer. Their approach results in significant inhibition of tumor ...

Study in mice suggests personalized stem cell treatment may offer relief for multiple sclerosis

February 22, 2018
Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis ...

Scientists find molecular link between Vitamin A derivative and mouse intestinal health

February 22, 2018
New research shows that all-trans-retinoic acid (atRA), the active form of vitamin A, regulates immune system responses in the mouse intestine by controlling expression of the protein HIC1 in cells known as innate lymphoid ...

Protein active in life-threatening allergic reactions is a promising target for therapy

February 22, 2018
Prospects for inhibiting the most dangerous symptoms of allergic reactions may be brighter with the publication of a new study that identifies a possible target for drug therapies. Research conducted at Cincinnati Children's ...

Recommended for you

Ambitious global virome project could mark end of pandemic era

February 23, 2018
Rather than wait for viruses like Ebola, SARS and Zika to become outbreaks that force the world to react, a new global initiative seeks to proactively identify, prepare for and stop viral threats before they become pandemics.

Forecasting antibiotic resistance with a 'weather map' of local data

February 23, 2018
The resistance that infectious microbes have to antibiotics makes it difficult for physicians to confidently select the right drug to treat an infection. And that resistance is dynamic: It changes from year to year and varies ...

Scientists gain new insight on how antibodies interact with widespread respiratory virus

February 22, 2018
Scientists have found and characterized the activity of four antibodies produced by the human immune system that target an important protein found in respiratory syncytial virus (RSV), according to new research published ...

Study reveals how kidney disease happens

February 22, 2018
Monash researchers have solved a mystery, revealing how certain immune cells work together to instigate autoimmune kidney disease.

Past encounters with the flu shape vaccine response

February 20, 2018
New research on why the influenza vaccine was only modestly effective in recent years shows that immune history with the flu influences a person's response to the vaccine.

Building better tiny kidneys to test drugs and help people avoid dialysis

February 16, 2018
A free online kidney atlas built by USC researchers empowers stem cell scientists everywhere to generate more human-like tiny kidneys for testing new drugs and creating renal replacement therapies.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.