Immunotargeting of catalase to the pulmonary endothelium alleviates oxidative stress and reduces acute lung transplantation injury
Immunotargeting of catalase to the pulmonary endothelium alleviates oxidative stress and reduces acute lung transplantation injury
复制标题
DOI：
10.1038/nbt806
复制
发表时间：
2003-04-01
影响因子：
46.9
通讯作者：
Muzykantov, VR
中科院分区：
文献类型：
--
作者：
Kozower, BD;Christofidou-Solomidou, M;Muzykantov, VR
血管免疫靶向可以促进治疗药物快速和特异性地递送到内皮细胞。我们在肺移植体内模型中研究了抗氧化酶过氧化氢酶靶向肺内皮是否能减轻氧化应激。静脉注射的酶与血小板内皮细胞粘附分子-1抗体结合，在肺血管中积累，并在长时间的冷藏和移植中保持其活性。过氧化氢酶免疫靶向供体大鼠可增强肺内皮的抗氧化能力，减轻氧化应激，改善缺血再灌注损伤，延长肺移植物可接受的冷缺血期，改善移植肺移植物的功能。这些发现证实了血管免疫靶向作为一种减少内皮损伤的药物递送策略的治疗潜力。该策略的潜在应用包括改善临床肺移植的结果和治疗各种内皮疾病。
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.