NEW YORK (TIP): Pulmonary fibrosis is a chronic, deadly disease that affects five million people worldwide. It is irreversible, its cause is poorly understood, and it has a median survival of only about three years. A new study by a team led by Indian-American scientist Dr Arul Veerappan of Dr Silvers Lab of Weill Cornell Medical College of prestigious Cornell University in New York implicates mast cells-an immune cell involved in allergic asthma-in the development of idiopathic pulmonary fibrosis could lead to new, more effective therapies.
The study is published in DNA and Cell Biology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. In the article “Mast Cells: A Pivotal Role in Pulmonary Fibrosis,” Dr. Arul Veerappan and colleagues from Weill Cornell Medical College, New York, NY, showed that in mice unable to produce mast cells, a chemical trigger known to cause pulmonary fibrosis does not result in disease. However, when the researchers introduced mast cells into the lungs of these mice, disease protection was reversed and the mice developed pulmonary fibrosis. The authors identify a role for two key compounds produced by mast cells-histamine and renin-and propose that they promote fibrogenesis when mast cells are activated early in the course of the disease.
Editor-in-Chief Carol Shoshkes Reiss, Departments of Biology and Neural Science, New York University, New York says, “Randi Silver’s lab has shown, in this compelling paper that mast cells contribute to the pathogenesis of pulmonary fibrosis. These observations are important and may lead to the development of new therapeutic modalities to prevent deterioration of lung function.” Dr. Arul Veerappan had earlier proved that 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 led by Dr Arul Veerappan at Weill Cornell Medical College explained 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.
The genesis of the new study came through the efforts of the study’s lead author Dr. Arul Veerappan. 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. “That’s a big achievement, because it supports the notion that the mechanism we have discovered is not just a laboratory phenomenon – it’s actually occurring in the living human lung,” co-senior author Dr. Roberto Levi, professor of pharmacology at Weill Cornell Medical College notes. New research suggests that local renin production may also be crucial in diseases marked by tissue fibrosis (stiffening). In fact, Dr. Silver’s lab is now looking at the role locally produced renin might play in a rare, deadly illness called idiopathic pulmonary fibrosis (IPF), where lung tissue becomes increasingly inflexible over time.