October 18, 2010

Scientists Identify Novel Role for Lipids in Pneumonia

Photo of a doctor viewing a chest x-ray

A study of mouse and human lung fluid revealed a fatty molecule that may play an unexpected role in the breathing difficulties of pneumonia. The finding could open the door to entirely new approaches for treating this sometimes-deadly condition.

Pneumonia is a serious lung disease and a leading cause of death in all age groups. Bacteria are the most common cause in adults, but respiratory viruses and fungal infections can also trigger the disease. Pneumonia arises when the airways become inflamed and filled with fluid in response to an infection. Symptoms include coughing, fever, chills and trouble breathing.

Bacterial pneumonia is usually treated with antibiotics. With the emergence of drug-resistant bacteria, scientists have been seeking new therapies that target underlying disease mechanisms rather than targeting the microbes. To date, few non-antibiotic therapies have been found to improve the outcomes of patients with severe pneumonia.

To learn more about at how bacterial pneumonia harms the lungs at the molecular level, a research team led by Dr. Rama Mallampalli at the University of Pittsburgh School of Medicine took a closer look at the fluid that naturally bathes the airways and tiny air sacs. The study was supported primarily by NIH’s National Heart, Lung and Blood Institute (NHLBI) and the U.S. Department of Veterans Affairs.

As reported in the October 2010 issue of Nature Medicine, the researchers analyzed lung fluid from humans and mice with pneumonia. They discovered abnormally high levels of a fatty molecule, or lipid, called cardiolipin. Cardiolipin is typically found in the outer membranes of mitochondria and bacteria, but it’s also known to be a minor component of healthy lung fluid.

When the scientists administered cardiolipin to mice, the animals’ lung function declined and the resulting tissue damage appeared similar to human pneumonia. Additional experiments confirmed that elevated cardiolipin appears to harm lung tissue.

The researchers identified a molecular pump, called Atp8b1, in lung cells that normally helps to keep cardiolipin levels in check by removing the molecule from lung fluid. Mice with defective Atp8b1 had elevated cardiolipin in lung fluid and were highly susceptible to pneumonia. ATP8b1 is also known to be defective in a human lung disease that raises the risk for pneumonia.

Experimental treatments that either blocked cardiolipin activity in lung fluid or that enhanced activity of the Atp8b1 pump were shown to reduce lung injury and improve survival in mice with experimental pneumonia.

“Our study reveals some of the molecular steps that can lead to lung injury after infection and shows us new avenues for pneumonia therapy that don’t have to target bacteria, as antibiotics do,” says Mallampalli. The researchers are now working to develop techniques for treating lungs with compounds that can bind tightly to cardiolipin and reduce lung injury.

—by Vicki Contie

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