What sparks that smoldering destruction remained a mystery until a consortium of researchers led by Baylor College of Medicine found that certain dendritic cells in the lung – the cells that "present" a foreign antigen or protein to the immune system – provoke production of destructive T-cells that attack a key protein called elastin, leading to death of lung tissue and emphysema.
A report of their work appears in the current issue of Science Transformational Medicine. The National Heart, Lung and Blood Institute estimates that 2 million Americans have emphysema, most of them over the age of 50 years. People with emphysema find it harder and harder to breathe as the lung's air sacs or alveoli are destroyed, causing holes in the lung and blocking airways. They have difficulty exchanging oxygen as their lungs become less elastic. Cigarette smoking is the greatest risk factor for the disease that contributes to as many as 100,000 deaths each year.
In previous work, Dr. Farrah Kheradmand, associate professor of medicine – pulmonary and immunology at BCM, and colleagues had shown that T-helper cells and some enzymes in the lung destroyed tissue in the lungs of emphysema patients. She credits BCM graduate student Ming Shan with pushing the project forward with the work in the current report.
She and her colleagues found that a subset of antigen-presenting cells in the lung are programmed to turn peripheral blood cells into the cells that are activated and are associated with autoimmune inflammation. They also found that elastin peptides can activate T cells –a sign that elastin is acting as an auto-antigen.
"This has implications for something that is important and biologically relevant," said Kheradmand. "Smokers are also at risk for diseases of the blood vessels such as the carotid artery and aorta. These blood vessels are also enriched in elastin. We believe that particular cells circulating in the body could react to elastin molecule at these remote sites."
This may help explain some of the cardiovascular and other complications associated with smoking tobacco. For example, skin is rich in elastin. The skin of smokers loses elasticity.
"We believe that this systemic inflammation that may initially affect the lung could also affect other parts of the body," she said.
She and fellow senior author Dr. David Corry, professor of medicine – pulmonary and immunology, and her colleagues used lung tissue taken from emphysema patients who were undergoing surgery anyway to determine which cells are present and their functions in the lung.
"These live cells are the center of what we studied," she said.
She and her colleagues found that some patients did not have the elastin-specific cells in their lungs, even though they had smoked.
"The Holy Grail is to find smokers who are destined to develop auto-reactive cells before the disease is fully manifested," she said. She said they hope to come with a test for T-cells that attack elastin that could be used in the doctor's office. However, she said, such a test would only identify patients at higher risk for emphysema and other elastin-associated diseases. It would not identify people at higher risk of lung cancer, for example.
"It is not a good excuse to smoke or continue smoking," she said.
Others who took part in the study include Han-Fang Cheng Li-zhen Song and Luz Roberts of BCM, Linda Green and Joan Hacken-Bitar of the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Joseph Huh and Faisal Bakaeen of MEDVAMC and BCM, Harvey O. Coxson and Claudine Storness-Bliss of Vancouver General Hospital in British Columbia, Canada; Mahesh Ramchandani of The Methodist Hospital in Houston, and Seung-Hyo Lee of the Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Funding for this work came from the U.S. National Institutes of Health and the American Heart Association.
For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy