Leaky Lungs
What do visiting a smoky bar and cooking with a wok in a small kitchen have in common? Both could cause “leakiness” between the endothelial cells that line the blood vessels in the lungs.
“It’s been shown that people who go to a smoky bar who get into an automobile accident are more likely to develop adult respiratory distress syndrome (acute lung injury),” says Sharon Rounds, MD, professor of medicine and chief of medical service at the Providence VA Medical Center. She’s studying how cigarette smoke exposure increases the risk of lung injury.
She thinks the answer lies in a chemical called acrolein that is released in cigarette smoke as well as overheated cooking oils. Acrolein “alters the activity of the signaling molecules and causes the endothelial cells to no longer be as tight and impermeable a barrier to leakiness into the lung,” she says. Rounds is working with Qing Lu, DVM, PhD, to study how signaling molecules, including proteins called Rho GTPases and the enzyme focal adhesion kinase, change in lung endothelial cells after mice have inhaled cigarette smoke. The pair is also evaluating how activators of specific enzymes might be able to treat this leakiness and prevent further injury.
Rounds and Lu are part of the Vascular Research Laboratory, a group of clinicians and PhD researchers who study pulmonary circulation. Collectively, they run the gamut from basic cellular research to animal and human research to health services and epidemiology. “We publish together, and we’re pretty cohesive … but we are an island,” Rounds says. “The thing that’s great about BIRDs is that it’s brought us the opportunity to branch out.”
BIRDs has changed the research questions Rounds is asking in her lab, and she hopes that trainees will soon be able to join in. “I think they would benefit immensely from hearing what people have to say at the BIRDs meetings,” she says.
The group also fits nicely with the five-year, $10.1-million COBRE grant that Rounds administers. The grant supports cardiopulmonary vascular biology research projects underway in the labs of five junior investigators and three pilot investigators.
Rounds shares lab space with a COBRE core facility. The lab setting is lovely: in the summer, a large tree canopy fills the window; in the winter, the bright lights of downtown offer a different reward. Within the lab is equipment for isolating and characterizing cells and measuring lung and heart injury in small animals.
Lab manager Julie Newton, BS, shows off a sophisticated research toy: an instrument that takes pictures of thin pieces of lungs that have been fluorescently labeled. She flashes a beautiful, multihued image from a magnified mouse lung of glowing blue lung cell nuclei, green endothelial cells, and swaths of red, which are the dying cells. This particular lung came from a “smoking mouse,” she says—a mouse that had inhaled cigarette smoke in a special chamber. More cells are labeled in red in this lung, compared to a lung from a mouse that had not inhaled smoke, because cigarette smoke increases the number of lung endothelial cells that undergo programmed cell death (apoptosis).
Even setting aside the lab’s picturesque surrounds and sophisticated equipment, the VA is an ideal location for Rounds, who is dedicated to both clinical care and basic research—especially since cigarette smoking is common among veterans, as are lung cancer, emphysema, and bronchitis. “In the past,” she explains, “cigarettes were actually handed out to soldiers to calm their nerves, so to speak.”
Luckily, Rounds sees fewer young veterans addicted to nicotine than their counterparts from previous generations. But in this generation, addiction has been replaced by increased asthma and sinusitis—possibly caused during deployments where soldiers come into contact with dust storms and burn pits. “The burn pits were near all these big bases in Southwest Asia where they basically dispose of everything—human waste, ammunition, plastics,” she says.
Rounds is fond of her VA patients, and would love to take a discovery all the way from the bench to help them. “They are just wonderful patients, wonderful people,” she says. “Have I found a cure for a patient I saw in the clinic? No. I’d love to. … Maybe someday.”
