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by Jacqueline Ruttimann
One of the most common biopolymers on earth may sometimes cause asthma.
Upon encountering the allergen chitin (red), immune cells release interleukin-4 (green) and interleukin-13, causing an allergic reaction. Host cells (blue) may release the enzyme chitinase to preempt the immune response.
The culprit for some forms of asthma may not be blowing in the wind but rather swimming in the sea or pushing through the soil. HHMI investigator Richard M. Locksley of the University of California, San Francisco, and colleagues have identified it as chitin—nature's second-most-abundant biopolymer—which is found, for example, in the exoskeletons of shellfish, the powerful inner grinders of worms, and the cell walls of fungi and insects.
Many of these organisms, including cockroaches and dust mites, are associated with allergies. And a sizeable percentage of asthma—as high as 25 percent—has been detected in previously asymptomatic workers in shellfish-processing plants. While humans and other vertebrates do not produce chitin, our immune systems innately recognize and eliminate it from the body. When this response goes awry, the result could be inflammation of airways that sets off asthma.
To pinpoint the exact molecular mechanism, Locksley's team infected mice with common parasitic worms called helminths. These mice were genetically engineered with fluorescent probes in their immune systems that would light up when activated. The researchers then observed that the mice responded by producing interleukin-4 and interleukin-13, which are the immune-cell chemicals typically dispatched to attack an allergen invader.
Locksley and colleagues also increased the expression of a gene coding for the enzyme, acidic mammalian chitinase (AMCase), that normally breaks chitin down. When the mice expressed more AMCase than normal, the immune response to chitin was greatly reduced. Similarly, mice exposed to purified chitin that was pretreated with AMCase had attenuated allergic reactions. The team's results were published in the May 3, 2007, issue of Nature.
"It's been an intriguing finding that we're continuing to follow up on," says Locksley, who is now looking at human lung cells to see whether asthma patients have less of the enzyme or a weaker form.
Scientific Image: Steve Van Dyken/Locksley lab