Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune cells play surprising role in cystic fibrosis lung damage

17.03.2009
Immune cells once thought to be innocent bystanders in cystic fibrosis may hold the key to stopping patients' fatal lung disease. New findings from the Stanford University School of Medicine and Lucile Packard Children's Hospital show that white blood cells called neutrophils respond strongly to conflicting signals from cystic fibrosis patients' lungs, setting up a molecular fracas that may explain the patients' severe lung damage.

"Cystic fibrosis patients have a problem with turning down the inflammatory response in the lungs," said senior study author Rabindra Tirouvanziam, PhD, an instructor in pediatric pulmonary medicine. "We've found that patients' neutrophils become kind of schizophrenic, doing a number of things that are opposite to the textbook view of neutrophils' role."

The research, which will be published online March 23 in the Proceedings of the National Academy of Sciences, opens up new targets for cystic fibrosis treatment, Tirouvanziam said.

Cystic fibrosis is a genetic disease of the lungs and digestive system that affects about 30,000 people in the United States. Patients used to die in childhood, but the life expectancy for a child born today with cystic fibrosis is now 50 to 60 years. Although modern medications and dietary treatments do a good job of controlling the digestive aspects of the disease, patients still suffer serious lung problems. Thick, sticky mucus builds up in their lungs, and chronic inflammation and bacterial infections lead to the breakdown of lung tissue.

For years, scientists believed that cystic fibrosis patients' lung problems started when bacteria became trapped in the excess mucus in their lungs. Neutrophils showed up at the lungs in response to the invasive bacteria, the thinking went. Neutrophils are supposed to engulf and destroy bacteria, but something went wrong and the neutrophils quickly died in the lung, releasing tissue-destroying enzymes, scientists thought.

"This paradigm makes sense in a superficial way, but it has very little to do with clinical reality," Tirouvanziam said. Careful clinical testing in infants with cystic fibrosis has shown that lung inflammation with neutrophils occurs even in the absence of detectable infection. And Tirouvanziam's earlier research showed the immune cells stay alive in the lung for quite a while after they arrive.

So what are the live neutrophils doing in patients' lungs? The new findings surprised Tirouvanziam's team. After collecting fresh neutrophils from cystic fibrosis patients' sputum and analyzing them with fluorescence-activated cell sorting, the team discovered that signals from the patients' lung tissue were reprogramming live neutrophils with conflicting messages. The first set of signals switches on what Tirouvanziam calls "an ancient happiness pathway" — a chain of commands that tell the neutrophils that nutrients are plentiful, and that it's a good time to translate the cell's library of genes into new protein. The second pathway is a cellular alarm system associated with inflammation and stress.

"They're receiving a lot of signals at same time, and we think the happiness signals are messing them up completely," Tirouvanziam said.

His team now suspects the inappropriate activation of the "happiness signal" — the molecular target of rapamycin, or mTOR, cell signaling pathway — may trigger neutrophils to release large quantities of human neutrophil elastase, the enzyme that destroys the elastic fiber of lung tissue. In healthy individuals, neutrophils never release destructive human neutrophil elastase into nearby tissue.

Understanding the sequence of events that release the tissue-chewing enzyme in cystic fibrosis is important, Tirouvanziam said, because it could help researchers find new disease therapies. Drugs now given to improve patients' lung function target symptoms such as difficulty breathing, but don't do anything to alter neutrophils' behavior. Tirouvanziam hopes that will soon change.

Erin Digitale | EurekAlert!
Further information:
http://www.stanford.edu
http://mednews.stanford.edu
http://www.lpch.org

More articles from Health and Medicine:

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

nachricht Flexible sensors can detect movement in GI tract
11.10.2017 | Massachusetts Institute of Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

Im Focus: New nanomaterial can extract hydrogen fuel from seawater

Hybrid material converts more sunlight and can weather seawater's harsh conditions

It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...

Im Focus: Small collisions make big impact on Mercury's thin atmosphere

Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.

Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Taking screening methods to the next level

17.10.2017 | Life Sciences

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

‘Find the Lady’ in the quantum world

17.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>