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 How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

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: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>