An enzyme released by mast cells in the lungs appears to play a key role in the tightening of airways that is a hallmark of asthma pointing to a potential new target for treatment against the illness.
Reporting in the online edition of Proceedings of the National Academy of Sciences, a team at Weill Cornell Medical College explains that during an immune response, mast cells release the enzyme -- called renin -- which in turn produces angiotensin, a potent constrictor of the smooth muscle that lines airways.
Mast cells are normally present in small numbers in all organs, and are best known for their role in allergy, shock, wound healing and defense against pathogens.
"Back in 2005, our team was the first to discover that mast cells in the heart released renin locally, which elicited heart arrhythmias by triggering angiotensin production within the heart," explained co-senior author Dr. Roberto Levi, professor of pharmacology at Weill Cornell Medical College.
"Now, we've expanded those findings to the lungs, where similar mechanisms appear to work locally to help trigger constriction in the airway," he says.
Renin is no stranger to medical research -- for decades, doctors have known that the enzyme is produced by the kidney in relatively large quantities for systemic use throughout the body. But the Weill Cornell team was the first to discover that mast cells also produced their own "local" supply of the enzyme, at a variety of body sites.
"In the heart and now the lungs, this localized production of renin appears to have a profound effect on nearby tissues," says co-senior author Dr. Randi Silver, associate professor of physiology and biophysics at Weill Cornell.
"More study is needed, of course, but our finding suggests that drugs that target renin might prove effective agents in dampening asthma or other respiratory diseases," she says. "These types of 'renin inhibitors' are, in fact, currently being developed by the pharmaceutical industry right now."
The genesis of the new study came through the efforts of the study's lead author, Arul Veerappan, now a postdoctoral researcher in Dr. Silver's laboratory. He looked closely at rings of bronchial tissue from rodents, discovering that mast cells in these rings released renin along with other substances.
"You ended up getting the same biochemical cascade that we had seen elsewhere -- newly produced renin bringing about a local rise in angiotensin in tissues," Veerappan says.