Newly Discovered Proteins Associated with Cystic Fibrosis

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.