A surprise discovery in mice has linked a mysterious class of molecules to asthma and may bolster the theory that the respiratory disease is a misplaced reaction to parasites. The molecules, called chitinases, were long considered a primordial response to certain parasites and insects.
Chitinase breaks down the compound chitin, which is produced in the shells and outer surfaces of these animals. But because humans don't produce chitin, their half-dozen or so chitinase genes have often been dismissed as relics of evolution. High levels of one chitinase, however, have been linked to a rare inherited enzyme disorder called Gaucher disease.
Now, Yale University pulmonary specialist Jack Elias and his colleagues have tied a second chitinase, an enzyme called acidic mammalian chitinase, to a key inflammatory response in asthma. Elias, pulmonary scientist Zhou Zhu, and others had noticed crystals in the lungs of mice bred to have an asthmalike disease. When they purified the crystals, the team was astonished to learn that they'd hit on a chitinase.
Intrigued, Elias's group induced asthma attacks in their mice and then examined their lung tissue. The scientists found far more of the chitinase than in the lungs of healthy animals. Additional experiments revealed that a class of immune cells, T helper type 2 (Th2) cells, that many consider critical to triggering asthma prompted levels of the chitinase enzyme to soar. When Elias and his colleagues gave the sick mice a serum that blocked the chitinase, the animals' lung inflammation eased, they report in the 11 June issue of Science.
The scientists also studied lung tissue from humans with asthma and healthy controls. Those with asthma had high levels of the chitinase in their lungs; the chitinase was undetectable in those without the disease. The discovery may bolster the popular theory that in asthma patients, the body senses parasites where there aren't any and sends the immune system into overdrive. Chitinase is normally used by some parasites and insects to break down chitin; excess chitinase in asthmatics suggest that their immune systems are somehow tricked into thinking chitin is present when it's likely not.
"I think it's going to open up a whole new area of exploration," says William Busse, an asthma specialist at the University of Wisconsin Medical School in Madison, of the research. "A lot of people would have given up and said, 'This [chitinase] has nothing to do with anything.' They pursued it."