Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Teaming up to attack free radicals

24.03.2003


Antibody/enzyme combo protects transplanted lungs from oxidative stress damage


Protecting endothelial cells with targeted antioxidant enzymes (AOE). The AOE, catalase in this case, connected to an antibody binds to endothelial cells (EC) and detoxifies reactive oxygen species (ROS), which can cause free radical damage.



Researchers based at the University of Pennsylvania School of Medicine have combined the precision of antibodies with the power of an antioxidant enzyme to create a new way to protect transplanted lungs from oxidative stress – also known as free radical damage – before and during transplantation.

Their findings, presented in the April edition of Nature Biotechnology and available online now, demonstrate the therapeutic potential of immunotargeting as a drug delivery system. Oxidative stress causes some degree of damage in 15-20% of all transplants and is the leading cause of acute lung graft failure. By protecting the lungs from damage, the researchers have determined that they can increase lung-graft survivability and the length of time a donated lung can be kept in cold storage.


"It is a simple theory that has been difficult to put into practice: get an antibody that will go to a specific target and attach a therapeutic to go along for the ride," said Vladimir R. Muzykantov, MD, PhD, assistant professor in Penn’s Department of Pharmacology. "Endothelial cells – the cells that line the interior of blood vessels – bristle with possible targets for antibodies to cling to as they rush through the bloodstream. This targeted delivery of drugs has enormous potential for treating a variety of endothelial cell disorders, including cancer and cardiovascular and pulmonary disease."

To protect transplanted lungs against oxidative stress, Muzykantov and his colleagues chemically coupled catalase, an enzyme that detoxifies oxidants, with an antibody for the platelet-endothelial cell adhesion molecule-1 (PECAM). Their findings in animal models show that anti-PECAM/catalase hybrid construct strengthened antioxidant defenses, lessened free-radical damage, reduced transplantation-associated acute lung injury, and improved the overall survivability of the lung graft.

"All organs, and lungs in particular, suffer a great deal during the time they are removed, transported, and put in to another body." said Steven M. Albelda, MD, vice chief of the Pulmonary, Allergy, and Critical Care Division of Penn’s Department of Medicine. "In fact, our findings show that the anti-PECAM/catalase is most effective when given to the donor prior to organ removal, as it protects the lung when it is in cold storage."

According to the researchers, the PECAM molecule was an attractive target because there are a great many of them on the surface endothelial cells, even during times of physiological stress. Following transplant, the researchers were able to determine that the anti-PECAM/catalase conjugates accumulated in the blood vessels of the lungs and retained their activity for a prolonged period during cold storage, transplantation, and the restoration of blood flow.

"Endothelial cells are particularly vulnerable to oxidative stress but, unfortunately, most antioxidant enzymes do not last very long in the bloodstream," said Muzykantov. "By combining an antioxidant with an antibody, we can direct an enzyme to where it needs to be and keep it there."

According to Muzykantov, their research provides a proof-of-concept for this method of drug delivery. They are seeking to further streamline the process by which they can join the anti-PECAM antibody to the catalase enzyme in order to make the anti-PECAM/catalase into a more effective and easily produced therapeutic.

"This immunotargeting approach may be extremely valuable," said Muzykantov. "It could reduce injury during clinical lung transplantation and may dramatically increase the amount of time that lung grafts are stored, thereby increasing the pool of donor lungs for use in clinical transplantation. This approach could also likely be applied to other organ transplants."


Other Penn researchers involved in this paper include Melpo Christofidou-Solomidou from the Department of Medicine, and Thomas D. Sweitzer, Donald G. Buerk, and Silvia Muro from Penn’s Institute for Environmental Medicine. Researchers contributing from other institutions include Charalambos C. Solomides of Temple University, and Benjamin D. Kozower and G. Alexander Patterson of Washington University.

Funding for this research was provided by the National Institutes of Health and the American Lung Association. The anti-PECAM antibody was a gift from Dr. Marian Nakada, Centocor, Inc., of Malvern, Pennsylvania.

Greg Lester | EurekAlert!

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate satellite: Tracking methane with robust laser technology

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...

Im Focus: How protons move through a fuel cell

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...

Im Focus: A unique data centre for cosmological simulations

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...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

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)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>