Smoking Mice Lead To Emphysema Br...( St. Louis Sept. 26 1997 -- With the h...)

St. Louis, Sept. 26, 1997 -- With the help of some heavy-smoking mice, researchers at Washington University School of Medicine in St. Louis have discovered that lungs lacking a certain enzyme are apparently immune to emphysema. The discovery, described in the Sept. 26, 1997, issue of Science, throws serious doubt on conventional theories of the disease, and researchers are already using the finding to search for potential new drugs.

Steven D. Shapiro, M.D., associate professor of medicine and of cell biology and physiology at the School of Medicine, and colleagues found that mice genetically engineered to lack an enzyme called macrophage elastase showed no signs of emphysema even after inhaling the smoke of two unfiltered cigarettes a day, six days a week for six months. Such heavy smoking invariably causes emphysema-like symptoms in normal mice. "There hasn't been a new drug for emphysema in 20 years, and that was oxygen," Shapiro says. "Blocking this enzyme or related enzymes might give us a way to halt the disease."

Emphysema, almost always caused by smoking, robs lungs of their elasticity and leaves patients gasping for air. The lungs actually become overinflated, leaving no room for deep breaths. About 2 million Americans suffer from the disease.

Before this study, most researchers assumed that emphysema was caused by neutrophils, white blood cells that destroy foreign invaders and, occasionally, cause inflammation. According to the most widely-accepted scenario, neutrophils mount a counter-attack against smoke by congregating in the lungs and releasing inflammatory enzymes. The enzymes eventually break down elastic fibers in the lungs, causing a new case of emphysema.

But the prevailing theory had a shortcoming: lungs with emphysema don't have many neutrophils. Instead, they are full of macrophages, immune-system cells that eat bacteria and other intruders. Few thought macrophages played a role in emphysema because
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Contact: Chris Woolston
woolston@medicine.WUSTL.edu
314-286-0109
Washington University School of Medicine
22-Sep-1997

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