Yale Researchers Discover New Potential Asthma Therapeutic Targets Related To Parasites And Insects

Asthma is a disease produced by chronic inflammation of the airways. The AMCase protein was not previously thought to be involved in asthma. It was known to digest chitin, which is found in the outer wall of insects and parasites, and was not thought to be involved in inflammation.

"We found that if we block the AMCase protein with an antibody or if we use an inhibitor that prevents it from digesting chitin, we can decrease asthma-like inflammation," said senior author Jack A. Elias, M.D., the Waldemar Von Zedtwitz Professor of Medicine and Section Chief and Professor of Internal Medicine/Pulmonary and Critical Care. "Since chitin is not present in our mouse models, this protein must be acting on something other than chitin. We do not know what that is right now."

The team also found that the protein is present in the airways of human asthmatics but not in control lungs. "We are hopeful that blocking AMCase in human asthmatics will have a similar beneficial effect on the human disease," said Elias.

The inflammation seen in asthma is driven by specialized lymphocytes (white blood cells), called T helper type 2 cells. Other cell types promote different kinds of inflammation in which the AMCase protein is not made in high amounts. If this protein is blocked, it will only alter asthmatic type inflammation, but not the other types of inflammation, which are needed to fight many infections.

"We also found that interleukin-13, a protein that is well known to be important in asthmatic type inflammation is required for increased production of AMCase," said Elias. "Another protein associated with asthmatic type inflammation, interleukin-4, was not required."

"The way that blocking AMCase inhibits inflammation is unusual in that we did not prevent T helper-2 cell activation," Elias added. "We prevented production of other proteins which are needed to recruit inflammatory cells into the lung."

Other authors on the study included first author Zhou Zhu, Tao Zheng, Robert J. Homer, Yon-Keun Kim, Ning Yuan Chen, Lauren Cohn and Qutayba Hamid.