18 Aug 2015

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

SASKATOON – 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 insights that could benefit cystic fibrosis patients. Their findings are published today in the Proceedings of the National Academy of Sciences (PNAS).

“We discovered that the airway responds to inhaled bacteria by secreting airway surface liquid,” said Juan Ianowski, assistant professor of physiology in the U of S College of Medicine and lead researcher on the team. “This is a previously unknown component of the innate immune defense.”

The discovery suggests that by helping this component function better – for example, through early and sustained use of antibiotics – it may be possible to improve lung function in cystic fibrosis patients.

Airway surface liquid, or ASL, is part of the “mucociliary” system. The ASL consists of a mucus layer that traps bacteria, dust and other particles and a thinner liquid layer on which the mucus “floats” as it is swept out of the lungs by tiny hair-like cilia. The ASL also has bactericidal properties, not only trapping potential disease-causing microbes, but inactivating and killing them.

Over the last decade, scientists have hypothesized that in cystic fibrosis, a mutation to a gene called CFTR interferes with the production of ASL. The lungs of people with the mutation – as well as test animals such as pigs, ferrets and mice – all fail to respond to inhaled irritants and other threats that would prompt strong ASL production in healthy individuals. Also, the ASL that is produced has poor bactericidal properties.

Until now, however, it has never been possible to answer two central questions: do bacteria trigger ASL secretion in the airways, and what is the role of CFTR in the process? The research team came up with a novel synchrotron-based method that unlocked the answer.

“We developed a technique to measure airway fluid, which to our knowledge is the only way to do this,” said Dean Chapman, a professor of anatomy and cell biology and co-author on the PNAS paper. Chapman holds the Canada Research Chair in X-Ray Imaging. A specialist in the medical and biological applications of synchrotron light, Chapman also leads the Biomedical Imaging and Therapy beamline at the CLS, one of only a few such facilities in the world.

Armed with the new technique, the researchers exposed swine tracheas to three of the most common bacteria that cause problems with cystic fibrosis patients. All prompted increased production of ASL, confirming its role as part of the immune system’s response to inhaled bacteria – a role that is compromised by the mutated CFTR gene.

The work, funded through a grant from Cystic Fibrosis Canada, supports a growing body of evidence that this inability to clear microbes from the lungs is at the root of airway disease in cystic fibrosis patients. Patients are afflicted with a persistent cough with thick mucus, wheezing and shortness of breath, and frequent lung infections. Eventually, the disease destroys lung tissue and contributes to illness and early death.

From left: graduate student Jay Luan, University of Saskatchewan Assistant Professor and Cycstic Fibrosis Canada Researcher Dr. Juan Ianowski, BMIT Scientist Dr. George Belev, Canada Research Chair in X-ray imaging Dr. Dean Chapman, BMIT Scientist Dr. Tomasz Wysokinksi.
Cite: Luan, Xiaojie, et al. "Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea." Proceedings of the National Academy of Sciences 111.35 (2014): 12930-12935. doi:10.1073/pnas.1406414111

About the CLS:

The Canadian Light Source is Canada’s national centre for synchrotron research and a global centre of excellence in synchrotron science and its applications. Located on the University of Saskatchewan campus in Saskatoon, the CLS has hosted over 2,000 researchers from academic institutions, government, and industry from 10 provinces and 2 territories; delivered over 32,000 experimental shifts; received over 8,300 user visits; and provided a scientific service critical in over 1,000 scientific publications, since beginning operations in 2005.

CLS operations are funded by Canada Foundation for InnovationNatural Sciences and Engineering Research CouncilWestern Economic Diversification CanadaNational Research Council of CanadaCanadian Institutes of Health Research, the Government of Saskatchewan and theUniversity of Saskatchewan.

Synchrotrons work by accelerating electrons in a tube to nearly the speed of light using powerful magnets and radio frequency waves. By manipulating the electrons, scientists can select different forms of very bright light using a spectrum of X-ray, infrared, and ultraviolet light to conduct experiments.

Synchrotrons are used to probe the structure of matter and analyze a host of physical, chemical, geological and biological processes. Information obtained by scientists can be used to help design new drugs, examine the structure of surfaces in order to develop more effective motor oils, build more powerful computer chips, develop new materials for safer medical implants, and help clean up mining wastes, to name a few applications.

For more information visit the CLS website 
For photos to accompany this story and more images from the CLS visit our photo gallery

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