Arsenic exposure and airway remodeling after acute influenza infection

Project Leader

Mitsuo Matsuoka, M.D., Ph.D.
Assistant Professor, Medicine
Geisel School of Medicine at Dartmouth


Richard I. Enelow, M.D.
Professor, Medicine
Geisel School of Medicine at Dartmouth

A major interest in the lab is to understand basic mechanisms underlying inflammatory response and tissue repair after lung injuries, as these mechanisms relate to development of a variety of inflammatory lung diseases. The current area of focus is respiratory virus induced airway injury and a role of arsenic exposure in development of post-infection airway remodeling. Airway remodeling is a key structural change of airway walls seen in chronic airway diseases such as asthma, COPD, cystic fibrosis and bronchiectasis. It is characterized by smooth muscle hyperplasia, vascular proliferation, increase in bronchial glands and collagen deposition.

Exposure to arsenic is a major health concern and occurs throughout the world, primarily via contaminated drinking water and foods. Chronic arsenic exposure has been shown to increase risk for lung diseases as well as many other health problems. In a small are of Chile, a large-scale arsenic exposure occurred in 1950 to 1970. The epidemiological data indicated a striking relationship between the exposure and airway diseases including COPD and bronchiectasis.
Respiratory virus infection is another factor that has been widely implicated in pathogenesis of chronic airway diseases. It is still not well understood, however, how acute viral infection could impact on the development of the chronic structural changes of the airways, when clearance of viruses occur fairly quickly. Generally, longstanding inflammation is considered necessary for airway remodeling to develop, but this may not be always the case. In mice models, acute experimental infections with Influenza, RSV, Sendai or Sendai virus rarely, if ever, result in significant airway remodeling. However, we have found that mice pre-exposed to a low level of arsenic can develop significant airway remodeling events upon influenza infection despite their viral clearance is preserved. Exposure to arsenic per se does not induce inflammation or morphological changes in the lungs. This raises the fascinating possibility that the airway remodeling observed after acute viral challenge in arsenic treated mouse may be a pathologic process distinct from the effects of prolonged virus carriage or long standing inflammation.

Overall goal of the project is to address a novel and critical question of how previous Arsenic exposure confers susceptibility to an altered inflammatory response, including changes in macrophage and T lymphocytes populations, and/or tissue repairing process upon subsequent respiratory infection, by using our mouse influenza infection model.