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Proteins in lungs of patients with cystic fibrosis

An unusual distribution of two proteins has been found in the lungs and airways of people with cystic fibrosis. //

Researchers feel that this finding can help in determining how the disease progresses. The proteins were uncovered as a result of the human genome project and are thought to play a role in the body's immune system. 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. It was presented at a meeting of The American Physiological Society, "Physiological Genomics and Proteomics of Lung Disease,".

"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 fo und 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 i ncreased 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.

Source-Eurekalert
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