Immunotargeting of catalase to the pulmonary endothelium alleviates oxidative stress and reduces acute lung transplantation injury
| Autor: | G. Alexander Patterson, Benjamin D. Kozower, Donald G. Buerk, Steven M. Albelda, Silvia Muro, Melpo Christofidou-Solomidou, Vladimir R. Muzykantov, Thomas D. Sweitzer, Charalambos C. Solomides |
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| Rok vydání: | 2003 |
| Předmět: |
Endothelium
medicine.medical_treatment Biomedical Engineering Cold storage Bioengineering Pharmacology medicine.disease_cause Applied Microbiology and Biotechnology Antioxidants Rats Sprague-Dawley Drug Delivery Systems Animals Humans Medicine Lung transplantation Lung Cells Cultured biology business.industry Antibodies Monoclonal Catalase medicine.disease Rats Inbred F344 Rats Platelet Endothelial Cell Adhesion Molecule-1 Transplantation Oxidative Stress medicine.anatomical_structure Reperfusion Injury Immunology biology.protein Molecular Medicine Endothelium Vascular Immunotherapy business Reperfusion injury Oxidative stress Lung Transplantation Biotechnology |
| Zdroj: | Nature Biotechnology. 21:392-398 |
| ISSN: | 1546-1696 1087-0156 |
| Popis: | Vascular immunotargeting may facilitate the rapid and specific delivery of therapeutic agents to endothelial cells. We investigated whether targeting of an antioxidant enzyme, catalase, to the pulmonary endothelium alleviates oxidative stress in an in vivo model of lung transplantation. Intravenously injected enzymes, conjugated with an antibody to platelet-endothelial cell adhesion molecule-1, accumulate in the pulmonary vasculature and retain their activity during prolonged cold storage and transplantation. Immunotargeting of catalase to donor rats augments the antioxidant capacity of the pulmonary endothelium, reduces oxidative stress, ameliorates ischemia-reperfusion injury, prolongs the acceptable cold ischemia period of lung grafts, and improves the function of transplanted lung grafts. These findings validate the therapeutic potential of vascular immunotargeting as a drug delivery strategy to reduce endothelial injury. Potential applications of this strategy include improving the outcome of clinical lung transplantation and treating a wide variety of endothelial disorders. |
| Databáze: | OpenAIRE |
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