St. Louis - Scientists have elucidated a critical step in emphysema, a progressive destruction of lung tissue that often occurs in smokers. A new study shows that debris of a protein called elastin attracts a class of immune cells that deal additional damage. The research was presented here October 14 at the International Conference on biology and pathology of the extracellular matrix.
Emphysema is the fourth leading cause of death in the United States. The damage is irreversible and no treatment except giving patients extra oxygen. In emphysema, a class of immune cells called macrophages flock to the lungs. There they churn enzymes that break down elastin, a fibrous protein which contributes to lung their shape and flexibility. The resulting fragments attract several types of immune cells, which led pulmonologist Steven Shapiro of the University of Washington in St. Louis to suspect that the fragments could also attract the same sort of macrophages that began the destruction of the elastin first.
Shapiro and colleagues have liquid lungs of the smoker in the upper half of a plastic container of which the two compartments are separated by a membrane. When they put human macrophages in the lower compartment filled with a cell culture medium, cells were grown to the membrane. This move was blocked when they added an antibody that latches on elastin fragments. And Shapiro and colleagues injected elastin fragments directly into the lungs of mice. Soon, macrophages were gathered in the lungs and began to produce an enzyme that destroys elastin.
Macrophages can hang in the lungs of smokers long after they get rid of their habit, so the damage can probably last for years, Shapiro said. That is why he is now looking for a compound that prevents cells from attacking elastin in mice.
The conclusion does not explain how emphysema is started, said pulmonologist Yale University Paul Noble, but it shows how it continues: Once the macrophages collect in the lungs, elastin fragments keep them coming. The next question, Noble said, is why all smokers have emphysema, while all have lungs macrophages. Perhaps genetic differences cause different immune responses, Noble said: "The response to these fragments ... may explain why some people smoke for 80 years and never get emphysema."
The National Emphysema Foundation
Emphysema information from the American Lung Association
National Emphysema Treatment Trial NIH
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