April 25, 2011

Broccoli Compound May Combat COPD

Photo of broccoli

In chronic obstructive pulmonary disease (COPD), damage to immune cells limits the lungs’ ability to fight off bacterial infections. According to a new study, boosting the activity of a specific molecule in these cells can restore their defensive powers.

COPD is the third leading cause of death nationwide. It’s often brought on by cigarette smoking. COPD can cause shortness of breath, wheezing and coughing, among other symptoms. In patients with COPD, immune cells called macrophages lose their ability to engulf and remove bacteria, making the lungs more vulnerable to infection. Infection can lead to inflammation, which is a major cause of impaired lung function and death in these patients. Until now, no one knew how to reverse this damage to the macrophages.

A team of scientists at Johns Hopkins University, led by Drs. Shyam Biswal and Robert Wise, investigated why macrophages don’t work properly in COPD patients. Previous research suggested that a process called oxidative stress might be to blame. Oxidative stress occurs when the body can’t effectively neutralize damaging compounds called peroxides and free radicals.

A molecule called Nrf2 can cause cells to make more antioxidants, which neutralize these harmful compounds. Previous studies found reduced Nrf2 activity in severe COPD. The scientists suspected that increasing Nrf2 activity might restore the ability of macrophages to remove bacteria. To test their theory, the team used a chemical called sulforaphane, which is known to activate Nrf2. A precursor of sulforaphane is found in broccoli. The research was cosponsored by NIH’s National Heart, Lung and Blood Institute (NHLBI) and National Institute of Environmental Health Sciences (NIEHS). The results appeared in the April 13, 2011, issue of Science Translational Medicine.

The researchers first took macrophages from the lungs of patients with moderate COPD. When they treated these macrophages with sulforaphane, they saw higher Nrf2 levels in the cells. Sulforaphane treatment also boosted the ability of cultured macrophages to clear 2 of the major types of bacteria that infect COPD patients. Macrophage uptake of bacteria rose 300% after treatment, whether the cells came from smokers or non-smokers.

Experiments in mouse and human cells revealed that sulforaphane, through Nrf2, increases levels of a receptor called MARCO on macrophages. MARCO activity was necessary for macrophages to engulf bacteria after sulforaphane treatment. Mice exposed to smoke had lower levels of MARCO. Furthermore, smoke-exposed mice genetically engineered to lack Nrf2 had more lung inflammation and higher levels of bacteria.

The team next tested treatment approaches that might help COPD sufferers. They gave sulforaphane with a nebulizer to mice exposed to smoke and found that the mice’s lungs showed reduced inflammation and bacterial burden. The researchers also gave human COPD patients broccoli sprout extract enriched with sulforaphane for 2 weeks. The patients taking the extract had higher levels of MARCO and Nrf2-controlled antioxidants in their blood cells. A NHLBI-sponsored clinical trial is now being conducted to test if sulforaphane can provide relief to patients with COPD.

"This research may help explain the long-established link between diet and lung disease, and raises the potential for new approaches to treatment of this often-devastating disease," says Wise.

— by Allison Bierly, Ph.D.

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