title: Lung endothelium targeting for pulmonary embolism thrombolysis.
abstract: BACKGROUND
  Pulmonary embolism occurs frequently in hospitalized patients. Thrombolytic therapy, currently used as the major treatment, has often been associated with severe bleeding complications and has thereby been life-threatening. We have developed a novel therapeutic method based on our newly created pulmonary endothelium-specific antibody.
  
  
  RESULTS
  We isolated membrane proteins of rat pulmonary vascular luminal endothelium and obtained a monoclonal antibody, RE8F5, which antigen was uniquely expressed by the pulmonary capillary endothelium. In vivo biodistribution showed that RE8F5 and its urokinase conjugate were rapidly and specifically accumulated in lung. Urokinase and the conjugate were compared in rats with pulmonary, hepatic, and lower-limb embolus. In a pulmonary embolus model, the conjugate exhibited 12-fold enhanced thrombolytic potency over urokinase, whereas plasma fibrinogen and bleeding time were unaffected. In 2 other models, no significant thrombolysis was induced by the conjugate. In contrast, thrombolysis by urokinase was found to be comparable to the pulmonary embolus model. In addition, urokinase caused significant consumption of fibrinogen in all experiments.
  
  
  CONCLUSIONS
  These data show that urokinase equipped with lung endothelium-specific antibody is an ideal treatment for pulmonary embolism, with a high efficacy of thrombolysis and low risk of bleeding.
authors: Institute of Molecular Medicine and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China.
authors: Bi-Sen
authors: BS
authors: Ding
authors: Ying-Jiang
authors: YJ
authors: Zhou
authors: Xin-Yuan
authors: XY
authors: Chen
authors: Jing
authors: J
authors: Zhang
authors: Pei-Xiang
authors: PX
authors: Zhang
authors: Zi-Yong
authors: ZY
authors: Sun
authors: Xiang-Yang
authors: XY
authors: Tan
authors: Jian-Ning
authors: JN
authors: Liu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000918:Antibody Specificity; D002196:Capillaries / Q000737:chemistry / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006470:Hemorrhage / Q000517:prevention & control; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply*; D008565:Membrane Proteins / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D015912:Thrombolytic Therapy; D014018:Tissue Distribution; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D018796:Immunoconjugates; D008565:Membrane Proteins; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator