Newly Discovered Proteins
Associated With Cystic Fibrosis
FORT LAUDERDALE, FL (Nov. 3, 2006) _ Researchers
have found a highly unusual distribution of two proteins in the lungs
and airways of people with cystic fibrosis, a discovery that could be a
step in determining how the disease progresses. The proteins, first
uncovered as a result of the human genome project, are thought to play a
role in the body’s immune system.
The discovery is preliminary, but intriguing:
Finding out more about the proteins could help sort out the immune
system’s role in cystic fibrosis, a genetic disease that attacks the
lungs and other organs and dramatically shortens life expectancy.
The study “Comparative expression of SPLUNC1,
SPLUNC2 and LPLUNC1 in normal and diseased lungs,” was carried out by
Lynne Bingle of the University of Sheffield School of Clinical
Dentistry, Sheffield, United Kingdom, and Colin Bingle, University of
Sheffield Medical School, Sheffield. They will present the study at a
meeting of The American Physiological Society, “Physiological
Genomics and Proteomics of Lung Disease,” on Nov. 3. The meeting
takes place Nov. 2-5 in Fort Lauderdale.
“Our results show unique expression domains for
(the proteins) within the airways and suggest that alterations in
expression of these putative innate immune molecules may be associated
with lung disease,” the authors wrote.
Recently discovered
proteins
“We’ve shown these proteins to be expressed in
places like the upper airways, nose and mouth, where many bacteria and
infectious agents are found,” Bingle said. These tiny molecules are
thought to be part of the first line of the body’s defenses against
infectious agents, Bingle said.
The human genome project localized the PLUNC
(palate, lung and nasal epithelium clone) gene to chromosome 20. A
genetic locus in this region directs the production of a family of at
least 10 proteins. Some of the proteins are short, referred to as “SPLUNCs,”
while others are long, referred to as “LPLUNCs.”
Researchers have found that these proteins locate
in specific places in the bodies of healthy people. Because these
proteins are found in different areas, researchers speculate that they
may have slightly different functions and may fight different infectious
agents.
Investigation with
cystic fibrosis
People with cystic fibrosis have a faulty gene,
which normally controls the movement of salt into and out of cells and
this controls the movement of water, too, Bingle explained. In a patient
with cystic fibrosis, there is too little salt and water on the outside
of cells lining the airways. This means that the normally thin
protective layer of mucus becomes thick and very difficult to move.
It is very difficult for the patient to cough up
the thick mucus, so the airways get clogged. The trapped mucous becomes
a haven for infectious agents, which leads to long-term infection,
inflammation and scarring. Most patients will eventually need lung
transplants in order to survive, she said.
In this study, the researchers compared the tissue
of 21 cystic fibrosis patients -- all of whom had end stage disease and
were scheduled for a transplant -- to healthy tissue. The healthy tissue
was obtained from 10 patients undergoing surgical removal of a lung
tumor. The researchers used the healthy portion of lung tissue which is
usually excised along with the tumor.
The study looked at tissue samples from the lung’s
upper airway, just below the trachea, and from lower down in the airway,
in the peripheral lung, where gas exchange takes place.
This lower region of the lung has small airways as
well as the gas-exchange tissue. They used a staining technique to find
SPLUNC1, SPLUNC2 and LPLUNC1.
In normal lungs:
-
SPLUNC1 is found predominantly in the upper airways,
rarely in the smaller airways and is absent in the gas-exchange
tissue of the peripheral lung.
-
LPLUNC1 is found in both the small airways and in the
upper airways
-
SPLUNC2 is found in the mouth, but not in the lungs
The study found that the presence of SPLUNC1 is
“massively increased in the small airways of the lungs of people with
cystic fibrosis,” Bingle said. “It is really difficult to find SPLUNC 1
in similar airways from the normal lung.”
LPLUNC1 also increases significantly in the small
airways of people with cystic fibrosis compared to normal tissue, Bingle
noted. It is normal to have LPLUNC1 in this
region, but people with cystic fibrosis have a much greater
amount of it here.
The study found no differences in SPLUNC2 between
the diseased and normal lungs. SPLUNC2 appears to be exclusively
expressed in the mouth.
A step in the fight
against cystic fibrosis
These findings could become a way to prevent cystic
fibrosis related lung damage, most of which occurs because of the
constant infections these people suffer, Bingle said. The body’s immune
reaction to the infection also damages the lungs, “so knowing how these
immune reactions happen could help doctors prevent them or harness them
to fight the infection before it becomes established,” she said.
The media can attend this fascinating conference,
or request an interview with Dr. Bingle, by contacting Christine
Guilfoy, at
cguilfoy@the-aps.org or at (301) 634-7253. For reporters who cannot
attend, arrangements can be made in many cases for telephone interviews
with scientists. Please go to
http://www.the-aps.org/meetings/aps/ftlauderdale/index.htm for more
about the program.
The
American Physiological Society was founded in 1887 to foster basic and
applied bioscience. The Bethesda, Maryland-based society has 10,500
members and publishes 14 peer-reviewed journals containing almost 4,000
articles annually.
APS
provides a wide range of research, educational and career support and
programming to further the contributions of physiology to understanding
the mechanisms of diseased and healthy states. In 2004, APS received
the Presidential Award for Excellence in
Science, Mathematics and Engineering Mentoring.
