Clues to Cause of Chronic Lung Disease

Overactive machrophages trigger a cascade of events that lead to emphysema, asthma, and chronic obstructive pulmonary disease, according to Australian researchers. Their findings were reported in the September 2002 issue of the Journal of Experimental Medicine.

An enzyme called Hck plays a role in activating macrophages, part of the immune system in the lung. Normally locked in an inactive state, Hck unlocks and becomes active in the presence of foreign bodies or disease. When the researchers made a change to one amino acid in the enzyme in mice, it forced the enzyme into a permanently active state, signaling the macrophages to defend the lung against disease. The permanently active macrophages triggered a disease process that mimics the one found in humans suffering from chronic lung disorders. Prior US research had found Hck as largely redundant in the control of macrophages.

"The lining of the airways began to change and accumulate huge amounts of mucus. Elastic fibers built up around the airways, leading to fibrosis, which restricts the airways, reduces their elasticity, and causes scarring of the airways. Over time, other enzymes released by the macrophages started to eat away the lung,” said Gary Anderson, associate professor at the Ludwig Institute for Cancer Research (Melbourne, Australia), who worked with the research team of Dr. Matthias Ernst.

Finding Hck's lock and how to control it will open the way to effective drug treatments for COPD and other chronic lung disorders, say the researchers.




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