Unusual protein distribution enhances CF knowledge

Scientists have discovered an unusual distribution of two proteins in the lungs and airways of people with cystic fibrosis could form the basis of a therapy that could better define the immune system's role in cystic fibrosis.

Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage. In the US, approximately 30,000 people have CF, most are diagnosed by six months of age.

Approximately 1 in every 25 people of European descent is a carrier of a cystic fibrosis mutation. Although CF is less common in these groups, approximately 1 in every 46 Hispanics, 1 in every 65 Africans and 1 in every 90 Asians carry at least one abnormal CFTR gene.

The researchers from the University of Sheffield, have called this discovery "intriguing," despite it being at the preliminary stage.

In the study, 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 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.

They used a staining technique to find SPLUNC1, SPLUNC2 and LPLUNC1.

The human genome project localised 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."

The study found that the presence of SPLUNC1 isincreased in the small airways of the lungs of people with cystic fibrosis. Usually, it is 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. 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.

Because these proteins are found in different areas compared to the bodies of healthy people, the researchers speculated that they may have slightly different functions and may fight different infectious agents.

"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.

"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," added Colin Bingle, University of Sheffield Medical School, Sheffield.

"These tiny molecules are thought to be part of the first line of the body's defences against infectious agents."

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.

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.

"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," said Lynne Bingle of the University of Sheffield School of Clinical Dentistry, Sheffield.

"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 added.