The research, conducted in mice, suggests that the protein, a cytokine named EMAPII, could provide a target for drugs to treat emphysema, said Irina Petrache, M.D., associate professor of medicine at the Indiana University School of Medicine. The research was posted online May 16 for the June edition of The Journal of Clinical Investigation.
Emphysema, a form of chronic obstructive pulmonary disease (COPD) that affects nearly 5 million people in the U.S alone, is caused by the destruction of cells that transfer oxygen from the lungs to the blood, along with inflammation in the lungs. Cigarette smoking is the most common cause of emphysema.
The cytokine EMAPII – a type of cell-signaling molecule – is normally part of the process of early lung development. Research had previously found that EMAPII could cause the death of cells that line blood vessels – endothelial cells – and inflammation, but it had not been identified as the molecular culprit at work when cigarette smoking inflicted its damage on the lungs.
"The fact that we could have a single target affecting two major processes made us excited about looking for it in response to smoking," said Dr. Petrache, the Floyd and Reba Smith Investigator in Respiratory Disease at IU.
When the researchers induced emphysema in mice exposed to cigarette smoke, tests showed the mice had elevated levels of the EMAPII cytokine. In other tests, the scientists also found elevated levels of the cytokine in the lungs of patients with COPD.
The researchers also found that the cell death caused by the EMAPII resulted in the release of enzymes that cause more production of EMAPII, causing a vicious cycle of elevated cytokine levels and more cell death.
Members of the research team, led by first author Matthias Clauss, Ph.D., IU associate research professor of cellular and integrative physiology, created an antibody designed to specifically target EMAPII and block its activity. The mice received an inhaled version of the antibody during their third month of smoking. They then were exposed to a fourth month of smoking without the treatment.
The mice receiving the treatment had significantly less cell death and inflammation and improved lung function compared to the smoking mice who did not receive the treatment. Moreover the benefits to the treated mice continued even after the treatment stopped.
Next steps include optimizing the duration of the antibody treatments to determine whether they continue to have an effect after the animals have stopped smoking, she said. Plans also call for work to measure levels of the cytokine in large numbers of human emphysema and COPD patients to determine whether it can be used as a biomarker to measure the presence, severity or type of lung disease.
Considerable research work remains before an EMAPII antibody might be ready for testing in humans, Dr. Petrache said.
Additional researchers on the project included Robert Voswinckel and Sandeep Nikam of the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; Gangaraju Rajashekhar, Ninotchka L. Sigua, Natalia I. Rush, Kelly S. Schweitzer, Krzysztof Kamocki, Amanda J. Fisher, Yuan Gu, Bilal Safadi, Homer L. Twigg III and Robert G. Presson of the IU School of Medicine; Heinz Fehrenbach of the Leibniz Center for Medicine and Biosciences, Borstel, Germany; Ali Ö. Yildirim of the German Research Center for Environmental Health, Helmholtz Zentrum, Munich, Germany; Walter C. Hubbard of the Johns Hopkins University, Baltimore; Rubin M. Tuder of the University of Colorado Health Science Center, Denver; and Sanjay Sethi of New York University School of Medicine.
Funding for the research was provided by the National Institutes of Health, Deutsche Forschungsgemeinschaft, the German Clusters of Excellence initiative and the European Commission.
Eric Schoch | EurekAlert!
Cystic fibrosis alters the structure of mucus in airways
28.06.2017 | University of Iowa Health Care
Mice provide insight into genetics of autism spectrum disorders
28.06.2017 | University of California - Davis
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
28.06.2017 | Physics and Astronomy
28.06.2017 | Physics and Astronomy
28.06.2017 | Health and Medicine