Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Boosting blood system protein complex protects against radiation toxicity

25.06.2012
New research in Nature Medicine shows that boosting a protein pathway in the body's blood making system protects mice from otherwise fatal radiation poisoning.

Scientists in the multi-institutional study – posted online by the journal on June 24 – say their findings open the potential for new treatments against radiation toxicity during cancer treatment or environmental exposures – such as in a nuclear explosion or accident.

By identifying a target-specific intervention to protect the hematopoietic system against radiation toxicity, the study addresses a largely unmet challenge, according to the researchers.

"These findings suggest that pharmacologic augmentation of the activity of the Thbd-aPC pathway by recombinant Thbd (thrombomodulin) or aPC (activated protein C) might offer a rational approach to the mitigation of tissue injury and lethality caused by ionizing radiation," the scientists write in their manuscript. "Recombinant human aPC has undergone extensive clinical testing in patients, and recombinant soluble human Thbd is currently being investigated for efficacy in antithrombotic therapy in humans. Our data encourage the further evaluation of these proteins for their radio-mitigating activities."

The study reveals a previously unknown function of the Thbd-aPC pathway in radiation mitigation. The pathway is normally known for its ability to prevent the formation of blood clots and help the body fight infections. The researchers found the pathway helps blood cells in the bone marrow recover from injury caused by radiation exposure. They demonstrated that pharmacologic boosting of this pathway with two drugs tested for the treatment of thrombosis or infection (recombinant Thbd and aPC respectively) can be used in mice to prevent death caused by exposure to lethal doses of radiation.

In all instances of treatment with recombinant soluble Thbd or aPC, the result was accelerated recovery of hematopoietic progenitor cell activity in bone marrow and a reduction in the harmful effects of lethal total body irradiation. When treatment was with aPC, these benefits occurred even when treatment was delayed for 24 hours.

The scientists caution their study involves early laboratory research in mice, so it remains to be tested how the findings may translate to human treatment. Researchers also need to determine exactly why the protective function of the targeted Thbd-aPC protein pathway seems to work so well in mice.

Researchers noted that the protective benefits of Thbd-aPC occurred only in vivo in irradiated mouse models. The researchers reported that overexpressed Thbd in irradiated laboratory cell cultures did not offer the same protective benefits, as the cells did not survive. This indicates the protective benefits of Thbd on blood making cells in irradiated mouse models depends on the help of additional cells or molecules in the body, which the researchers are trying to identify in a follow-up study.

The study involves extensive multi-scientist collaborations that combined previously independent lines of research by groups at Cincinnati Children's Hospital Medical Center and the University of Ulm, Germany (led by Hartmut Geiger, PhD, Division of Experimental Hematology/Cancer Biology and the Department of Dermatology/Allergic Diseases); the University of Arkansas, Little Rock (led by Martin Hauer-Jensen, MD, PhD, Division of Radiation Health, the College of Pharmacy and the Central Arkansas Veterans Healthcare System); the Blood Research Institute in Milwaukee, Wis. (led by Hartmut Weiler, PhD); and The Scripps Research Institute in La Jolla, Calif. (led by John H. Griffin, PhD, Department of Molecular and Experimental Medicine).

The research team said the current study exemplifies a global shift to multi-investigator projects that allow a combination of varied expertise by scientists tackling complex problems from the perspective of their respective fields. This approach requires the willingness of investigators to share unpublished data and engage in an open collaboration. The researchers also said the study underscores the importance of continued federal funding for leading edge basic research that can benefit human health.

The study was supported by funding from The National Institutes of Health, as well as the U.S. Department of Veterans Affairs and the Edward P. Evans Foundation.

Additional co-authors on the study include Snehalata A. Pawar, Edward J. Kerschen, Kalpana J. Nattamai, Irene Hernandez, Hai-Po Liang, Jose A. Fernandez, Jose A. Cancelas, Marnie A. Ryan, Olga Kustikova, Axel Schambach, Qiang Fu, Junru Wang, Louis M. Fink, Karl-Uwe Petersen, Daohong Zhou and Christopher Baum, and the following institutions: Department of Experimental Hematology, Hannover Medical School, Hannover, Germany; the Desert Research Institute, Las Vegas, Nev.; PAION Deutschland GmbH, Aachen, Germany.

About Cincinnati Children's:

Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2012 Best Children's Hospitals ranking. It is ranked #1 for neonatology and in the top 10 for all pediatric specialties. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health. It is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org.

Nick Miller | EurekAlert!
Further information:
http://www.cchmc.org
http://www.cincinnatichildrens.org

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

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...

Im Focus: Quantum Particles Form Droplets

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...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

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,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>