Key receptor in bronchial asthma discovered

K. Frank Austen, MD, of the Inflammation & Allergic Diseases Research Section at Brigham and Women’s Hospital, along with colleagues Akiko Maekawa, Yoshihide Kanaoka, and Wei Xing, has identified a key receptor in bronchial asthma by experimenting with “knock-out” mice that fail to express the “classical” cysteinyl leukotriene receptors, revealing a new target for therapeutic intervention.  These findings appear in the October 13, 2008 issue of Proceedings of the National Academy of Sciences.

Past research has unveiled two cysteinyl leukotriene (potent lipid mediators of inflammation) receptors which have been the focus in determining a therapeutic treatment for bronchial asthma. Investigators previously cloned these receptors in mice and “knocked” them out, providing a mouse lacking both of the known receptors. They then found that mice lacking the “classical” receptors were fully responsive to the vascular effects of the cysteinyl leukotrienes, confirming that there is another receptor beyond the previous two that had been found. The researchers also discerned that the new-found receptor is particularly responsive to LTE4, the most abundant cysteinyl leukotriene, which has been unaddressed in previous treatment methods for bronchial asthma.

Moving forward, the researchers hope to clone the new receptor and knock it out, in order to study the mouse without the receptor.  This will also allow the researchers to breed the mouse with a mouse that has had the other two receptors knocked out, providing them with a mouse lacking all three cysteinyl leukotriene receptors. With this mouse, researchers can determine whether there are any additional cysteinyl leukotriene receptors.

(Source: Proceedings of the National Academy: Brigham and Women’s Hospital: October 2008)