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Biological Chemistry

Chopping Chitin Reduces Allergic Reactions

Medicinal Chemistry: Lung enzyme prevents immune response by breaking up the dust mite polysaccharide

by Michael Torrice
May 25, 2015 | APPEARED IN VOLUME 93, ISSUE 21

Credit: Wikimedia Commons
Dust mites have exoskeletons made from chitin.
Credit: Wikimedia Commons
Dust mites have exoskeletons made from chitin.

For many people with asthma, house dust mites trigger allergic reactions, including lung inflammation. Now, a team of researchers has demonstrated that the activity of an enzyme found in lungs may stop this immune reaction by chopping up chitin, the polysaccharide that makes up the mites’ exoskeleton. The findings could lead to future therapies for patients allergic to the household pests. Richard A. Flavell of Yale University School of Medicine and colleagues genetically engineered mice to express a defective version of acidic mammalian chitinase, which is one of two chitin-chomping enzymes in the lungs. The mutant enzyme can bind chitin but not cleave it. The engineered mice showed a significantly greater allergic response to inhaled dust mites than normal animals did (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1073/pnas.1507393112). Through further experiments, the team found that the extent of the allergic reaction depended on the size of chitin chunks given to the mice: Uncleaved chitin triggered large responses, but chopped-up chitin did not. Unlike the response to intact chitin, lung cells absorb the small polysaccharide fragments, leading to inactivation of pathways that trigger an immune response.



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