Cystic fibrosis scientists discover abnormal response to lung infections

October 6, 2017 by Lana Haight, University of Saskatchewan
Xiaojie "Jay" Luan, PhD student, and Juan Ianowski prepare the sample stage at the BMIT beamline. Credit: University of Saskatchewan

"For a very long time, there has been discussion about whether cystic fibrosis was a bacteria-infection problem, an inflammation problem, or an immune system problem," said Juan Ianowski, the lead author of the paper published today in the prestigious Nature Communications journal.

Ianowski, associate professor in the Department of Physiology at the University of Saskatchewan, and a team of 18 researchers have concluded that the genetic mutation that causes prevents normal secretion of airway surface liquid including mucus. Using a new imaging technique they developed at the Canadian Light Source, they determined that the production of airway surface liquid in response to bacteria is abnormal, and might lead to a cascade of infection and inflammation in lungs as the incurable disease progresses.

"Most patients are born with healthy lungs and as time passes, they start developing infections and inflammation. The infections are cleared and a new one occurs, and then there is an infection and it's cleared and a new one occurs. Eventually, the infections are permanent and the bacteria never leave the lungs," said Ianowski.

Cystic Fibrosis Canada estimates that one in every 3,600 children born in Canada has cystic . It is the most common affecting Canadian children and young adults, according to the organization's website.

People with healthy lungs inhale between 5,000 and 14,000 germs every day. These germs are caught in their airways by a with antimicrobial properties that kills the germs. Tiny hairs called cilia then push the germs out of the respiratory tract and the body clears the mucus and the germs.

The hypothesis that people with cystic fibrosis do not have normal production of mucus in response to inhalation of pathogens was developed decades ago, but until now, there was no way to test it.

Ianowski and his team spent seven years developing the synchrotron-based method needed to analyze the production of mucus in a living animal. The normal layer of is as thin as 80 microns. That's thinner than a strand of hair.

At the Canadian Light Source, they imaged the normal lungs of pigs focusing on the liquid layer, measuring it and analyzing its production. They also were able to image how the liquid in the airway reacts when bacteria are introduced. Then, they repeated the process with pigs who modeled cystic fibrosis.

"We discovered and showed for the first time ever that the normal response to inhalation of pathogens is producing liquid. This is a process that depends on CFTR (cystic fibrosis transmembrane conductance regulator) expression. So if you don't have normal CFTR, it doesn't work. In CF pigs, this response is absent," explained Ianowski.

Explore further: New synchrotron imaging technique reveals how cystic fibrosis makes lungs vulnerable to infection

More information: Xiaojie Luan et al. Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens, Nature Communications (2017). DOI: 10.1038/s41467-017-00835-7

Related Stories

New synchrotron imaging technique reveals how cystic fibrosis makes lungs vulnerable to infection

August 18, 2014
University of Saskatchewan researchers working at the Canadian Light Source (CLS) synchrotron have developed a new imaging technique that reveals a hitherto unknown component of the immune system in the lungs, one that promises ...

Cystic fibrosis alters the structure of mucus in airways

June 28, 2017
Mucus is important for maintaining healthy lungs. Inhaled particles, including bacteria and viruses, get trapped in mucus and then cilia—tiny hair like projections on the surface of the airway cells—sweep the mucus out ...

Repurposing an old drug to treat cystic fibrosis airway disease

June 2, 2016
The lungs contain a thin layer of fluid known as the airway surface liquid (ASL), which helps protect against pathogens. The appropriate ASL volume, pH, and ionic composition are required for optimal airway defense. Cystic ...

Mucus retained in cystic fibrosis patients' cells leads to potentially deadly infections

February 18, 2015
Cystic fibrosis is a genetic disorder that affects one out of every 3,000 children in populations of Northern European descent. One of the key signs of cystic fibrosis is that mucus lining the lungs, pancreas and other organs ...

Benefits of cystic fibrosis drug ivacaftor reported in pre-school children for the first time

January 21, 2016
The oral drug ivacaftor appears to be safe and could be beneficial to young children between the ages of 2 and 5 with a specific type of cystic fibrosis, according to new research published in The Lancet Respiratory Medicine ...

Improved airway-targeted gene delivery in a pig model of cystic fibrosis

September 8, 2016
Cystic fibrosis (CF) is characterized by accumulation of thick mucus in the lungs and is associated with a high incidence of bacterial infection. Mutations in the gene encoding CF transmembrane conductance regulator (CFTR) ...

Recommended for you

Team develops new way to grow blood vessels

August 17, 2018
Formation of new blood vessels, a process also known as angiogenesis, is one of the major clinical challenges in wound healing and tissue implants. To address this issue, researchers from Texas A&M University have developed ...

New imaging technique can spot tuberculosis infection in an hour

August 16, 2018
Guided by glowing bacteria, researchers have devised an imaging technique that can diagnose live tuberculosis in an hour and help monitor the efficacy of treatments. That's particularly critical because many TB strains have ...

Obesity, infertility and oxidative stress in mouse egg cells

August 16, 2018
Excessive body fat is associated with negative effects on female fertility and pregnancy. In mice, maternal obesity impairs proper development of egg precursor cells called oocytes. In a recent paper published in Molecular ...

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

This matrix delivers healing stem cells to injured elderly muscles

August 15, 2018
A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method ...

Male tobacco smokers have brain-wide reduction of CB1 receptors

August 15, 2018
Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor", when compared with non-smokers, reports a study in Biological Psychiatry.

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.