Enzyme-Antibody Fights Oxidative Stress in Lung Transplants

Researchers have successfully coupled the antioxidant enzyme catalase to antibodies against platelet-endothelial cell adhesion molecule, PECAM-1, a molecule found in large numbers in lung tissue, in order to protect transplanted lungs from oxidative stress. Their work was reported March 24, 2003, in the online edition of Nature Biotechnology.

Oxidative stress causes some degree of damage in 15-20% of all transplants and is the leading cause of acute lung graft failure. To reduce this damage, investigators from the University of Pennsylvania School of Medicine (Philadelphia, USA; www.upenn.edu) created an "immunotargeting” agent by chemically attaching the enzyme catalase to PECAM.

"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,” explained Dr. Vladimir R. Muzykantov, assistant professor in the University of Pennsylvania's Department of Pharmacology.

Treatment of lung tissue with the 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.

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



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