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!
Antibiotic effective against drug-resistant bacteria in pediatric skin infections
17.02.2017 | University of California - San Diego
Tiny magnetic implant offers new drug delivery method
14.02.2017 | University of British Columbia
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
17.02.2017 | Medical Engineering
17.02.2017 | Medical Engineering
17.02.2017 | Health and Medicine