IOWA CITY, Iowa -- Human airway secretions include antimicrobial agents that normally protect the lungs from infection caused by inhaled bacteria and other microorganisms. A recent University of Iowa Health Care study suggests that high salt concentrations in the airways of people with cystic fibrosis prevent these antimicrobial factors from working effectively.
"The finding provides some new ideas about treatments for cystic fibrosis," said Sue M. Travis, Ph.D., UI research scientist and principal investigator.
Cystic fibrosis is the most common fatal inherited disease among Caucasians of Northern European descent and occurs in about one of every 2,000 births. Advances in treating the disease complications have increased the average survival age well beyond childhood; however, there is no cure.
In people with cystic fibrosis, whose lungs often become infected by inhaled microorganisms, airway antimicrobial activity has not been well understood. Previous research, including UI studies, showed that cystic fibrosis disrupts defenses against infection because the thin layer of liquid that lines the airways is saltier than in non-cystic fibrosis airways. Under normal conditions, antimicrobial peptides and proteins destroy the invasive microorganisms that land on the airway surface.
"Saltiness impairs the ability of the airway surface liquid to kill bacteria," Travis said. "We investigated specifically whether antimicrobials could kill bacteria in the salty conditions caused by cystic fibrosis."
The investigators studied how previously identified antimicrobial proteins, including lysozyme and lactoferrin, functioned in test-tube samples of human airway secretions taken from healthy people and people with cystic fibrosis.
"We found that the airway secretions, and the individual antimicrobial proteins, could kill bacteria in low-salt conditions, but they were less able to kill bacteria in high-salt concentrations," Travis said. "This inhibition of the antimicrobials by high salt may be why they fail to prevent infections in cystic fibrosis airways."
Travis explained how the findings could lead to potential therapies.
"Lowering the salt concentration in the cystic fibrosis airway might allow the antimicrobial factors to kill bacteria," she said. "Second, treatment using antimocribal factors that can function well in high-salt liquid could be beneficial."
"This work helps lay the foundation on which new treatments can be built for cystic fibrosis," said co-investigator Michael J. Welsh, M.D., UI professor of internal medicine, and physiology and biophysics.
Welsh, who is also a Howard Hughes Medical Institute investigator, led a previous study that suggests that the absence or malfunction of a specialized chloride channel in the cystic fibrosis airway causes the increased saltiness and that treatment could be based on correcting this salt imbalance.
In addition to Travis and Welsh, the other UI investigators for the antimicrobial study included Barbara-Ann D. Conway, Ph.D., postdoctoral associate in microbiology; Joseph Zabner, M.D., assistant professor of internal medicine; Jeffrey J. Smith, M.D., associate professor (clinical) of pediatrics; Norma N. Anderson, researcher in internal medicine; Pradeep K. Singh, M.D., fellow in internal medicine, and E. Peter Greenberg, Ph.D., professor of microbiology.
The study was funded in part by a grant from the Cystic Fibrosis Foundation. The findings were published in the May issue of the American Journal of Respiratory, Cell and Molecular Biology. The May issue also included a perspective on the study by Charles L. Bevins, M.D., Ph.D., of the Lerner Research Institute at the Cleveland Clinic Foundation.
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