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 Deep stimulation improves cognitive control by augmenting brain rhythms
04.04.2019 | Picower Institute at MIT

nachricht Black nanoparticles slow the growth of tumors
04.04.2019 | Technische Universität München

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: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>