Cystic fibrosis makes airways more acidic, reduces bacterial killing
The human airway is a pretty inhospitable place for microbes. There are numerous immune defense mechanisms poised to kill or remove inhaled bacteria before they can cause problems. But cystic fibrosis (CF) disrupts these defenses, leaving patients particularly susceptible to airway infection, which is the major cause of disease and death in CF.
Using a unique animal model of CF, a team of scientists from the University of Iowa has discovered a surprising difference between healthy airways and airways affected by CF that leads to reduced bacterial killing in CF airways. The finding directly links the genetic cause of CF -- mutations in a channel protein called cystic fibrosis transmembrane conductance regulator (CFTR) -- to the disruption of a biological mechanism that protects lungs from bacterial infection.
The study, published in the July 5 issue of Nature, shows that the thin layer of liquid coating the airways is more acidic in newborn pigs with CF than in healthy newborn pigs, and that the increased acidity (lower pH) reduces the ability of the liquid to kill bacteria. Moreover, making the airway liquid less acidic with a simple solution of baking soda restores bacterial killing in CF airways to almost normal levels.
Although the findings suggest that therapies that raise the pH of the airway surface liquid (ASL) may help prevent infection in CF, the researchers strongly caution that this discovery is at an early stage.
"Some have asked us if people with CF should inhale an aerosol that would raise the pH of the ASL," says Joseph Zabner, M.D., UI professor of internal medicine and senior study author. "At this point, we have no idea if that would help. And more importantly, it could be harmful."
"This was a very surprising finding," adds Alejandro Pezzulo, M.D., UI postdoctoral fellow and co-lead author of the study. "There have been many ideas as to what goes wrong in CF, but lack of a good experimental model has made it difficult to gain insight into how the disease gets started."
Unlike mouse models of the disease, the CF pigs develop lung disease that closely mimics what is seen in humans. Previous studies from the UI lab showed that although the airways of CF pigs are infection-free at birth, they are less able to get rid of bacteria than healthy airways and quickly become infected.
Testing bacterial killing in airways
The UI team, including Pezzulo and co-lead author Xiao Xiao Tang, Ph.D., a Howard Hughes Medical Institute postdoctoral research associate at the UI, developed a simple experiment to study bacterial killing by the ASL. They immobilized bacteria on a tiny gold grid and exposed these bacteria to ASL from CF-affected and healthy pigs.
The ASL from normal airways killed most of the bacteria very rapidly, whereas the ASL from CF-affected airways only killed about half of the bacteria, suggesting that in CF airways some bacteria would survive and go on to cause infection.
Further investigation showed that although many characteristics of the ASL in CF and non-CF pigs are similar, the ASL from CF airways is more acidic than the liquid from healthy airways.
When the scientists raised the pH of the ASL in CF pigs through inhalation of a solution of sodium bicarbonate (baking soda), the treated ASL was capable of killing most of the bacteria on the grid (just like ASL from normal airways). Conversely, lowering the pH of ASL from normal airways reduced bacterial killing. The finding confirms that pH is a critical factor for bacterial killing,
"This study explains why a defect in the CFTR channel protein leads to reduced bacterial killing and an airway host defense defect," Tang says. "Impaired bicarbonate transport because of the defective CFTR could cause increased acidity in the ASL, which the study shows reduces the ASL bacterial killing capability."
Potential clinical applications
Although the approach is not ready for clinical application, the study indicates that pH is a contributing factor in airway infection, suggesting that therapies that modify airway pH may potentially be helpful in preventing infection in CF patients.
In addition, the researchers believe that using the bacteria-coated grids to measure bacterial killing in airways might provide a simple way to test the effectiveness of other new CF therapies that currently are being developed.
Journal reference: Nature
Provided by University of Iowa
- Pigs provide clues on cystic fibrosis lung disease Apr 28, 2010 | not rated yet | 0
- Unraveling a new regulator of cystic fibrosis Sep 19, 2011 | not rated yet | 0
- Pig model of cystic fibrosis improves understanding of disease Mar 16, 2011 | not rated yet | 0
- Growth defects in cystic fibrosis may start before birth Nov 09, 2010 | not rated yet | 0
- Channeling efforts to fight cystic fibrosis Sep 17, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
Medical research 4 hours ago | 5 / 5 (1) | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research May 17, 2013 | 3.7 / 5 (3) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research May 17, 2013 | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research May 17, 2013 | 4 / 5 (1) | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
3 hours ago | not rated yet | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
3 hours ago | not rated yet | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
8 hours ago | not rated yet | 0
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
4 hours ago | 5 / 5 (1) | 0 |
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
3 hours ago | not rated yet | 0
The devastating effect of Alzheimer's disease on bilingual people has been thrown into focus in Canada, where the sudden loss of a second language can leave sufferers feeling like strangers in their own country.
6 hours ago | not rated yet | 0