At the Department’s monthly Medicine Research Conference on Fri., Sept. 30, two of Duke’s innovating pulmonary researchers explained how they’re using new paradigms to describe disease and illness in the lung.
A model system for idiopathic fibrosis
First up was Paul Noble, MD, professor of medicine and the chief of the Division of Pulmonary, Allergy and Critical Care Medicine. Before coming to Duke, Noble had started the interstitial lung disease groups at Johns Hopkins University and at Yale School of Medicine. He shared his latest research on severe pulmonary fibrosis in both animal and human models.
Pulmonary fibrosis is marked by the scarring and stiffening of the lungs. When it’s caused by autoimmune diseases or non-specific pneumonia, fibrosis can be cured. But idiopathic fibrosis, Noble said, is more akin to cancer than any other disease. Instead of metastasizing, cells called myofibroblasts respond to injury in the lung, and create the collagen that leads to progressive scarring. The pattern of injury, inflammation, repair and scar tissue repeats until a patient can no longer breathe.
“By the time I see them they may have three to five years,” Nobel said, referencing the more than 100,000 Americans who are diagnosed with this disease each year. There are currently no FDA-approved treatments for idiopathic fibrosis, which means lung transplant is the only option.
Noble presented his latest research on myrofibroblasts, the enzyme hyaluronan, and its corresponding CD44 receptor. In mouse models, a profusion of hyaluronan allowed myofibroblasts to act like cancer cells, destroying and invading the lungs. Blocking antibodies for CD44 and limiting the production of hylauronan led to a reduction of fibrosis in mice.
Noble is hopeful his latest research, which appeared in the Journal of Experimental Medicine, will lead to new treatment models in the near future.
“If we have a model system in animals and human cells,” said Nobel. “Then we can have a platform for new treatments.”
Macrophages’ hidden mission
The second presentation came from Robert Tighe, MD, medical instructor in the Division of Pulmonary, Allergy and Critical Care Medicine. He came to Duke in 2006 as a fellow in pulmonary and critical care.
Tighe spoke about two models of lung injury where macrophages were protective, and not detrimental, to lung health.
Tighe explained that macrophages are the soldiers of the body, cells recruited to destroy invaders, namely pathogens. In many lung diseases (asthma, COPD, lung cancer) macrophages are implicated, but, Tighe said, poorly understood. Tighe’s work looks at sub-populations of macrophages after lung injury, and suggests that these “Macs” have a protective element to their presence in the lung. Typically macrophages are identified as detrimental to lung health in animal models of human lung disease.
In his work on the lung’s response to ozone inhalation, Tighe identified novel resident lung macrophages present after ozone exposure. When genetically modified mice could not produce novel macrophages, ozone inhalation led to increased oxidative stress.
“The question now is how do we drive lung macrophages?” said Tighe. “If you can figure out ways to alter their function, you can use them to resolve injury.”
[toggle title_open="Close Me" title_closed="Relevant articles" hide="yes" border="yes" style="default" excerpt_length="0" read_more_text="Read More" read_less_text="Read Less" include_excerpt_html="no"]1. Tighe RM, Liang J, Liu N, Jung Y, Jiang D, et al. (2011) Recruited Exudative Macrophages Selectively Produce CXCL10 after Noninfectious Lung Injury. Am J Respir Cell Mol Biol 45:781-788.
2. Tighe RM, Li Z, Potts EN, Frush S, Liu N, et al. (2011) Ozone Inhalation Promotes CX3CR1-Dependent Maturation of Resident Lung Macrophages That Limit Oxidative Stress and Inflammation. J Immunol. [/toggle]
The Medical Research Conference is held the last Friday of each month.