Molecular Machinery That Kicks Asthma Into Gear Is Unveiled

Asthma affects about one in 12 people in the U.S. To find treatments for the chronic disease, scientists have long sought its underlying molecular causes. David B. Corry and Farrah Kheradmand of Baylor College of Medicine, in Houston, and colleagues recently unveiled part of asthma’s molecular pathway when they reported the results of some 20 years’ worth of research in Science (2013, DOI: 10.1126/science.1240342). By studying the response of lung cells from mice and humans to fungi—a frequent asthma trigger—the team determined that fibrinogen, a glycoprotein involved in blood clot formation, helps trigger asthma symptoms. The researchers showed that fungal protease enzymes cleave fibrinogen into bits, one of which binds and activates Toll-like receptor 4 (TLR4), a protein on cells lining the lungs. This cleavage probably happens in everyone’s lungs, Corry says, but to a greater degree in the lungs of asthmatics. Then, TLR4 somehow signals the “big guns” of the immune system—helper T cells, which ultimately induce an allergic response. Designing drugs to block TLR4, though, would be “playing with fire,” Corry says, because it regulates other parts of the immune system. But finding and blocking the relevant fibrinogen fragment might be a future strategy for asthma treatment.