Human lungs brush out intruders

Now, a study by Brian Button and colleagues from the University of North Carolina at Chapel Hill, NC, helps to explain how human airways clear such mucus out of the lungs. The findings may give researchers a better understanding of what goes wrong in many human lung diseases, such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and asthma.

The researchers' report appears in the 24 August issue of the journal Science.

"The air we breathe isn't exactly clean, and we take in many dangerous elements with every breath," explains Michael Rubinstein, a co-author of the Science report. "We need a mechanism to remove all the junk we breathe in, and the way it's done is with a very sticky gel called mucus that catches these particles and removes them with the help of tiny cilia."

"The cilia are constantly beating, even while we sleep," he says. "In a coordinated fashion, they push mucus containing foreign objects out of the lungs, and we either swallow it or spit it out. These cilia even beat for a few hours after we die. If they stopped, we'd be flooded with mucus that provides a fertile breeding ground for bacteria."

Until now, most researchers have subscribed to a "gel-on-liquid" model of mucus clearance, in which a watery "periciliary" layer acts as a lubricant and separates mucus from epithelial cells that line human airways. But this old explanation fails to explain how mucus remains in its own distinct layer.

"We can't have a watery layer separating sticky mucus from our cells because there is an osmotic pressure in the mucus that causes it to expand in water," Rubinstein says. "So what is really keeping the mucus from sticking to our cells?"

The researchers used a combination of imaging techniques to observe a dense meshwork in the periciliary layer of human bronchial epithelial cell cultures. The brush-like layer consists of protective molecules that keep sticky mucus from reaching the cilia and epithelial cells, thus ensuring the normal flow of mucus.

Based on their findings, Button and the other researchers propose a "gel-on-brush" form of mucus clearance in which mucus moves atop a brush-like periciliary layer instead of a watery one. They suggest that this mechanism captures the physics of human mucus clearance more accurately.

"This layer -- this brush -- seems to be very important for the healthy functioning of human airways," according to Rubinstein. "It protects cells from sticky mucus, and it creates a second barrier of defense in case viruses or bacteria penetrate through the mucus. They would not penetrate through the brush layer because the brush is denser."

"We found that there is a specific condition, below which the brush is healthy and cells are happy," Rubinstein explains. "But above this ideal condition, in diseases like CF or COPD, the brush becomes compressed and actually prevents the normal cilia beating and healthy flow of mucus."

The researchers explain that, whenever the mucus layer gets too dense, it can crash through the periciliary brush, collapse the cilia and stick to the cell surface.

"The collapse of this brush is what can lead to immobile mucus and result in infection, inflammation and eventually the destruction of lung tissue and the loss of lung function," says Rubinstein. "But our new model should guide researchers to develop novel therapies to treat lung diseases and provide them with biomarkers to track the effectiveness of those therapies."