Lynda S. Ostedgaard, MS, PhD, research associate professor in Pulmonary, Critical Care and Occupational Medicine, and David Stoltz, MD, PhD, professor in Pulmonary, Critical Care and Occupational Medicine, received a four-year, $2.5M R01 grant from the NIH’s National Heart, Lung, and Blood Institute. With this funding, Ostedgaard and Stoltz will examine the relative contributions of airway submucosal glands and surface epithelia to airway host defense and how these defenses interact in healthy and diseased airways.

In response to common lung disorders, lungs have evolved several airway defenses against bacteria, viruses, and toxic particles. These defenses include mucus secretion, antimicrobial proteins, and mucociliary transport. If these defenses are disrupted, inflammation and infection can cause lung disease. It has long been assumed that both submucosal glands and surface epithelia contribute to these defenses.

To test this assumption, the investigators generated pigs that are lacking submucosal glands, but retain surface epithelia in the airway. Initial studies with these pigs found that submucosal glands are required for normal antimicrobial activity and mucociliary transport.

“Comparing lungs with and without submucosal glands will provide the first direct evidence about whether and how submucosal glands are required for respiratory host defense,” Ostedgaard said. “The results will also lay a critical foundation for future tests of how submucosal glands contribute to airway disease pathophysiology.”

“Increased scientific knowledge of submucosal glands and interactions between surface epithelia/submucosal glands will provide a better foundation for understanding how airway surface liquid is regulated, how mucociliary transport is controlled, and ultimately identify desperately needed new targets for lung diseases,” Stoltz said.