Scott Boitano: Lung-Cell Signaling - A Life-Saving System in Peril

Dig deep into lung diseases, beyond the classic causes like cigarettes and working in a coal mine, and you'll come upon a few ancient hazards always in our air, water and dirt.

With Scott Boitano as your guide, you'll discover the effects on the lungs of a wide range of nature's toxicants, and at the top of the list is arsenic.

Arsenic disturbs the way certain lung cells, the ones in the lining, or epithelium, of the human airway, 'talk' to each other to carry out the lung's basic functions.

Boitano's focus is chronic obstructive pulmonary disease, or COPD. Many who have it simply call it emphysema or asthma. Boitano, an associate professor of physiology at The University of Arizona (UA) College of Medicine and a member of the Arizona Respiratory Center and BIO5, tracks 'intercellular signaling,' which is vital to all cells in the body, including lung epithelial cells, the cells of choice in the Boitano Lab. Boitano also is a member of the Southwest Environmental Health Sciences Center in the College of Pharmacy.

Imagine a snippet of conversation between two of those hard-working cells, at the Airway Epithelium Coffee Shop.

Cell 1 asks: How's your day?

Cell 2: Oh you know, staying alive. Got to rebuild some fences. Had a bad night. You know those microbes and toxicants, constantly poking holes in the epithelium.

Cell 1: Yep, me too. Have to work with the neighbors to move the latest mucous load. It is dirty in there.

Cell 2: Oops. Gotta run. Meetings with some macrophages. Immunity issues.

Cell 1: Catch you later.

Cell 2: You bet. Thanks for the intercellular communication. Later.

Such life-sustaining conversation is compromised by the arsenic in drinking water, according to new findings from the Boitano lab and his collaborators, and arsenic is everywhere. It's the world's No. 1 natural toxicant.

'The lung is one tough character,' said Boitano. But so are its enemies, especially arsenic. 'It's in the rocks, the dirt, and without intervention it has a way of showing up in water supplies all over the world.'

Arsenic is recognized as a hazard by the federal government and the World Health Organization. In 2006 the U.S. Environmental Protection Agency lowered allowable water supply levels from 50 parts per billion (ppb) to 10 ppb.

For 20 years, lung epithelial cells have been Boitano's research area, with arsenic effects becoming a key topic upon his move to The University of Arizona, where a significant collection of researchers are evaluating toxic effects of arsenic, and not just on the lung. The interactions between arsenic and the body's tissues affect lives not just in Chile, Mexico or Bangladesh, where arsenic in drinking water can reach very dangerous levels of up to 500 or even 1,000 ppb, but everywhere.

What's less well defined, Boitano says, is the long-term risk found in many American cities and towns where arsenic values are between 50 and 10 ppb. 'At that level, animal and cell models, and a scattered few population studies, suggest there may be specific toxicity, including specific effects that can alter lung function,' he says. 'We see some strong changes in how cells signal each other and in their way of repairing wounds.'

Boitano wasn't always a physiologist. He started college at the University of California, Berkeley as a business major, found it wasn't much fun, and looked to the classes he really enjoyed, biology. Before long he was off to Washington State University where his doctorate work involved cell signaling, and then to post-doctoral work at the University of California, Los Angeles and to the University of Wyoming as an assistant professor. He joined the UA in 2002.

Other ongoing work in the Boitano lab involves a fresh look at potential hazards in industrial nanoparticle production and pathogen interactions in the airway.

But that work will still center on lung epithelial-cell signaling. 'It's the basis of everything we do,' Boitano said.

Lung disease is expanding worldwide and is one of the top uncontrolled American epidemics. It leaves about 900,000 Americans too ill to work, costing billions in medical care and lost productivity. Most of the disease is linked to smoking and to environmental and occupational conditions, especially for miners and others who inhale particulates. Its victims run short of breath, often too weak to leave the house. It can lead to heart failure.

At least 12 million Americans have COPD, perhaps double that number. It kills more than 100,000 Americans a year, and is expected to become the third leading U.S. cause of death by 2020.

Boitano research page at BIO5
http://bio5.arizona.edu/bio5/database.php?cmd=search&faculty_id=2918&pub=32124&type=JOURNAL

Watch cell signaling
http://www.physiology.arizona.edu/labs/boitanolab/research/AEC/AECbiology.html

Boitano page at the Arizona Respiratory Center
http://www.arc.arizona.edu/whoswho_bio.php?EmpId=71

Boitano research page at the Department of Physiology
http://www.physiology.arizona.edu/articles/17

Boitano lab website
http://www.physiology.arizona.edu/labs/boitanolab/

Accomplishments

Scott Boitano, an associate professor of physiology at the UA College of Medicine, is a national leader in the study of how lung epithelial cells communicate.

He is a member of the Arizona Respiratory Center in the College of Medicine.

His work at BIO5 has been supported by grants from the National Institutes of Health and the American Lung Association. The Environmental Protection Agency has supported his research on arsenic biomarkers in the lung.

Boitano collaborates with chemists, clinical physicians and medical epidemiologists and colleagues at the Arizona Respiratory Center in the College of Medicine.