A special protein on the surface of cells once regarded as a troublemaker in the lungs actually plays an unexpected role as pulmonary protector—mitigating the damage caused by chronic lung illnesses such as chronic obstructive pulmonary disease, or COPD. So says a study published in January in the Journal of Clinical Investigation.1
COPD describes a category of diseases that includes emphysema, chronic bronchitis, and in some cases, asthma. It's a leading cause of death, illness, and disability in the United States. Smoking is the leading cause of the disease, but other etiologies include exposure to air pollutants, respiratory infections, and certain genetic factors.2 People with COPD can develop pulmonary hypertension as a complication, according to doctors.3
Protein Prophylaxis in the Lungs
Researchers at the University of Texas School of Medicine found that genetically deleting the protein from a group of mice with an experimental form of chronic lung disease resulted in increased inflammation, mucous, and pulmonary tissue damage, as well as early death.
A commentary on the study by researchers at the University of North Carolina stated that the finding is "surprising and unexpected", in light of the fact that suppressing this protein as a therapeutic strategy has been the focus of research to this point.4
"Some believe this receptor protein plays a detrimental role, and if you block it, you could improve asthma," said Michael Blackburn, PhD, associate professor of Biochemistry and Molecular Biology at the university, and the study's chief researcher. "[However], this study shows that if you remove this protein from a diseased lung, you'll make lung inflammation and damage worse."
Because of the finding, it appears the specialized protein "plays an important role turning on anti-inflammatory and tissue protective pathways," Blackburn explained.
At the Center of a Protective Process
This protein is one of four found on cell surfaces that connect with a signaling molecule known as adenosine. Adenosine is a byproduct of stress and tissue damage, and is found in elevated amounts in the lungs of people with asthma, Blackburn explained.
Earlier research by Blackburn and his team suggested that adenosine causes lung damage similar to what is found in asthma, COPD, and pulmonary fibrosis.5
Tinkering with a Destructive Molecule
In other research, Blackburn and colleague Rod Kellems, PhD, chairman of the department of Biochemistry and Molecular Biology at UT, developed a strain of mice that lacks the protein that normally lowers excessive amounts of adenosine. What they saw was a lethal form of lung diseases that quickly developed the features of COPD, pulmonary fibrosis and asthma in the animals.
"We believe if you could control specific aspects of the adenosine signaling pathway, you could control all three of these diseases," said Blackburn. "It will be important to examine the interplay of adenosine receptor signaling in other model systems [of pulmonary disease], as well as in the lungs of people suffering chronic lung disease to determine how these pathways might be manipulated to treat the progression of asthma and COPD."
1. Sun CX, Young HW, Molina JG, Volmer JB, Schnermann J, Blackburn MR. A protective role for the A1adenosine-dependent pulmonary injury. J Clin Invest 2005 Jan;115(1):35-43.
2. National Center for Environmental Health. Centers for Disease Control and Prevention (CDC). Facts About Chronic Obstructive Pulmonary Disease. Available at: http://www.cdc.gov/nceh/airpollution/copd/copdfaq.htm. Accessed March 3, 2005.
3. Barbera JA, Peinado VI, Santos S. Pulmonary hypertension in COPD: old and new concepts. Monaldi Arch Chest Dis 2000 Dec;55(6):445-9.
4. Tilley SL, Boucher RC. A1 antagonism in asthma: better than coffee? J Clin Invest 2005 Jan;115(1):13-6.
5. Chunn JL, Young HW, Banerjee SK, Colasurdo GN, Blackburn MR. Adenosine-dependent airway inflammation and hyperresponsiveness in partially adenosine deaminase-deficient mice. J Immunol 2001 Oct 15;167(8):4676-85.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
