Tobacco Smoke-Induced Cell Injury in Lung Compartments

Funded by a Grant from the State of Florida Department of Health


Tobacco smoke is a major cause of death and disability worldwide. It remains the single most preventable cause of death in the United States where one in five deaths is smoking related. Tobacco smoke is the major etiologic cause of chronic obstructive lung pulmonary disease (COPD) such as emphysema and chronic bronchitis where patients literally lose their ability to breathe. The economic cost of COPD in the United States was $24 billion in 2003. The state of Florida has a disproportionate share of the burden of patients with COPD with 900,000 patients and 10,000 deaths last year.

While tobacco smoke is composed of several noxious chemicals, a gaseous oxidative agent, nitric oxide (NO), is present in very large quantities and is recognized for its ability to cross tissue barriers and enter all major compartments of the lung. When nitric oxide encounters the cells that are present in lung compartments, it alters their structure and function by modulating proteins that regulate them.

The overall objective of the Team Science Program is to evaluate the interaction of tobacco smoke with key cells in lung compartments and to understand the molecular mechanisms whereby nitric oxide mediates changes in proteins and causes programmed cell death or suicide with subsequent loss of lung tissue and the disease manifestation of loss of breath. As tobacco smoke containing nitric oxide travels down the airway it encounters the layer of cells that line the walls of the bronchi and causes them to become leaky. At the end of the airway it reaches the air sacs where the sentinel defender cell called the alveolar macrophage gets activated to produce more nitric oxide. In the blood vessels tobacco smoke and nitric oxide mediate cell death and inhibit new blood vessel formation. These functional abnormalities are affected through nitric oxide-mediated alterations in cellular proteins.

Understanding the mechanisms whereby tobacco smoke causes lung cells to commit suicide and to decrease the number of blood vessels, which also become leaky, is the subject of this proposal and will allow us to develop therapeutic modalities to help patients. This Team Science Program will allow the University of Florida to fully develop its Center of Excellence in COPD. It will add a coordinated, synergistic research facet with shared resources and shared goals to ongoing clinical and educational COPD programs. This Team Science Program focuses on bringing state of the art research to the management of COPD and will have profound implications for the state of health of the people of Florida.