Lung endothelium targeting for pulmonary embolism thrombolysis. Academic Article Article uri icon

Overview

MeSH

  • Animals
  • Antibody Specificity
  • Capillaries
  • Drug Evaluation, Preclinical
  • Endothelium, Vascular
  • Female
  • Fibrinogen
  • Hemorrhage
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Rats
  • Rats, Sprague-Dawley
  • Specific Pathogen-Free Organisms
  • Tissue Distribution
  • Urokinase-Type Plasminogen Activator

MeSH Major

  • Antibodies, Monoclonal
  • Fibrinolytic Agents
  • Immunoconjugates
  • Lung
  • Pulmonary Embolism
  • Thrombolytic Therapy

abstract

  • 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. 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. 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.

publication date

  • December 9, 2003

has subject area

  • Animals
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Capillaries
  • Drug Evaluation, Preclinical
  • Endothelium, Vascular
  • Female
  • Fibrinogen
  • Fibrinolytic Agents
  • Hemorrhage
  • Immunoconjugates
  • Lung
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Pulmonary Embolism
  • Rats
  • Rats, Sprague-Dawley
  • Specific Pathogen-Free Organisms
  • Thrombolytic Therapy
  • Tissue Distribution
  • Urokinase-Type Plasminogen Activator

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1161/01.CIR.0000103685.61137.3D

PubMed ID

  • 14610017

Additional Document Info

start page

  • 2892

end page

  • 2898

volume

  • 108

number

  • 23