Immunotargeting of catalase to the pulmonary endothelium alleviates oxidative stress and reduces acute lung transplantation injury.
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.
Kozower
Benjamin D
BD
Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Christofidou-Solomidou
Melpo
M
Sweitzer
Thomas D
TD
Muro
Silvia
S
Buerk
Donald G
DG
Solomides
Charalambos C
CC
Albelda
Steven M
SM
Patterson
G Alexander
GA
Muzykantov
Vladimir R
VR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D000975:Antioxidants / Q000008:administration & dosage; D002374:Catalase / Q000008:administration & dosage*; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D016040:Lung Transplantation / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000975:Antioxidants; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D002374:Catalase