Clear airways: quelling a protein stops mucus overload.

Despite its lowly status, mucus plays a valuable role in the body. It provides a barrier against pathogens and lubricates tissues lining the air passages, gastrointestinal tract, and several other areas of the body. Too much mucus, however, can be annoying, unhealthy, and even deadly, as in chronic bronchitis, asthma, and cystic fibrosis.

By interfering with a protein that earlier research implicated in mucus secretion, scientists have countered overstimulation of mucus secretion in the airways of mice. The finding suggests that keeping this protein from its target might lead to a treatment for asthma in people, say the researchers in an upcoming issue of Nature Medicine.

Certain cells lining the lungs and other membrane-covered areas make and store mucus. These cells, called goblet cells, routinely release small amounts of the slippery substance. But the cells also secrete bursts of mucus in response to irritants. The mechanism behind the switch from healthy burst to aberrant secretion, as seen in people with asthma, remains unknown.

One protein that appears to be a factor in mucus secretion is myristoylated, alanine-rich C-kinase substrate, or MARCKS. In 2001, Kenneth B. Adler, a cell biologist at the College of Veterinary Medicine of North Carolina State University in Raleigh, and his colleagues suggested that MARCKS binds to tough sacs inside goblet cells and stimulates release of the mucus stored there. Adler's team then synthesized a small protein called MANS peptide (for myristoylated N-terminal sequence), which mimics part of the MARCKS protein. The peptide thwarted mucus secretions from cultured human-airway cells in lab tests.

The researchers now have further explored the role of MARCKS in an asthmatic reaction. First, they injected mice with albumin from egg whites to prime the animals for an allergic reaction to the substance. Two weeks later, the scientists exposed the animals' airways to albumin and the mucus-stimulating drug methacholine. Then, they deposited MANS peptide in the throats of some mice, while control mice received an inert peptide.

In a series of tests, the researchers found that the control mice secreted as much as five times the amount of airway mucus as mice getting MANS peptide did. Adler says the study also suggests that MANS peptide binds to molecules on the surface of the mucus-fined sacs in goblet cells, preventing MARCKS from stimulating secretion of the mucus.

"This study is very intriguing," says C. William Davis, a cell physiologist at the University of North Carolina School of Medicine at Chapel Hill. While MARCKS probably has a hand in regulating mucus secretion, he says, its role is "very complicated and not well understood." Other compounds within a cell might also stimulate mucus release, he says. Davis worries that inhibitors of mucus secretion might block activity of beneficial proteins.

STATS

31 million

People in the United States diagnosed with asthma