Navigation Links
Cystic fibrosis makes airways more acidic, reduces bacterial killing
Date:7/4/2012

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.


'/>"/>

Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-356-7124
University of Iowa Health Care
Source:Eurekalert

Related biology news :

1. Johns Hopkins researchers uncover genes at fault for cystic fibrosis-related intestinal obstruction
2. Researchers find critical regulator to tightly control deadly pulmonary fibrosis
3. Same gene that stunts infants growth also makes them grow too big
4. Modern hybrid corn makes better use of nitrogen, study shows
5. UH makes Princeton Reviews Green List 3 years in a row
6. Why spring is blooming marvelous (and climate change makes it earlier)
7. The loss of a protein makes jump the tumor to the lymph node
8. New study: Snacking on raisins significantly reduces overall post-meal blood sugar levels
9. Drugs from lizard saliva reduces the cravings for food
10. The absence of elephants and rhinoceroses reduces biodiversity in tropical forests
11. Hot sauce ingredient reduces beer belly fat as a weight-loss surgery alternative
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:11/21/2016)... Lithuania , Nov. 21, 2016   ... and object recognition technologies, today announced that the ... smart cards was submitted for the NIST ... successfully passed all the mandatory steps of the ... evaluation is a continuing test of fingerprint templates ...
(Date:11/15/2016)... ROCKVILLE, Md. , Nov. 15, 2016 /PRNewswire/ ... clinical company developing therapeutics focused on the gut ... public offering of 25,000,000 shares of its common ... its common stock at a price to the ... gross proceeds to Synthetic Biologics from the offering, ...
(Date:6/22/2016)... 22, 2016  The American College of Medical Genetics and ... Magazine as one of the fastest-growing trade shows during ... the Bellagio in Las Vegas . ... of growth in each of the following categories: net square ... number of attendees. The 2015 ACMG Annual Meeting was ranked ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... OXFORD, England , December 8, 2016 ... Company, has expanded its customisable SureSeqâ„¢ NGS panel range with ... - allowing fast and cost-effective study of variants in familial ... copy number variation (CNV) detection on a single small panel ... and hotspot content. This includes all exons for LDLR ...
(Date:12/8/2016)... Iowa (PRWEB) , ... December 08, 2016 , ... This ... asynchronous approvals for biotech crops. The authors focus on the economic effects in countries ... global approval of new biotech crops and the resultant risk of low level presence ...
(Date:12/8/2016)... Dec. 8, 2016 Eutilex Co. Ltd. today ... (US $18.9M) Series A financing. This financing round included ... Venture and SNU Bio Angel. This new funding brings ... KRW (US $27.7M) since its founding in 2015. ... the development and commercialization of its immuno-oncology programs, expand ...
(Date:12/7/2016)... ... 07, 2016 , ... Huffman Engineering, Inc. , a ... Certified System Integrator Partner. Huffman Engineering is the only Nebraska-based company recognized ... Integrator Partner certification gives customers confidence that our engineers are fully trained and ...
Breaking Biology Technology: