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!
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction