Described in the prestigious journal Cell and led by Richard Locksley at the University of California, a newest study has revealed that lung epithelial cells produces an enzyme that protects the lungs from a common harmful compound, chitin.
Chitin is a nitrogen-containing polysaccharide that makes up the cell walls of fungi and the exoskeletons of insects and crustaceans. Moreover, other organisms such as molluscs, cephalopods, and fish can also produce chitin. Some of these chitin producing organisms are pathogens in other species.
Chitin is one of the toughest natural materials and exists widely in the environment. Each time you take a breath, you may inhale bits of debris rich in chitin. There is evidence that mammalian exposure to chitin is related to upregulation and downregulation of inflammatory responses, including those involved in asthma.
It is well established that chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases, which are hydrolytic enzymes. Vertebrates also express chitinases, but little is known about their role in mammalian physiology. For the current study, the team looked at mammalian chitinases and found that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase).
Locksley and the team created genetically modified mice that do not produce AMCase. These AMCase-deficient mice showed premature morbidity and mortality, in comparison with the control mice. Moreover, the lungs of the AMCase-deficient mice showed the accumulation of chitin in the airways, absorbed less oxygen than normal, and exhibited signs of inflammation and fibrosis. These symptoms were decreased by restoration of lung chitinase activity by genetic or therapeutic approaches.
Next, the researchers analyzed samples of airway fluid from patients with interstitial lung disease. The measurement of chitin showed that these patients had much more chitin in their airways than healthy people. But these patients did not lack AMCase. Why this occurs requires further research.
Taken together, “These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction.”
Other researchers of the study include Steven Van Dyken, Hong-Erh Liang, Ram Naikawadi, Prescott Woodruff, Paul Wolters, and David Erle. (Cusabio offers AMCase and antibody.)