Restricted transport of anti-transferrin receptor antibody (OX26) through the blood-brain barrier in the rat

J Neurochem. 2001 Oct;79(1):119-29. doi: 10.1046/j.1471-4159.2001.00541.x.


Anti-transferrin receptor IgG2a (OX26) transport into the brain was studied in rats. Uptake of OX26 in brain capillary endothelial cells (BCECs) was > 10-fold higher than isotypic, non-immune IgG2a (Ni-IgG2a) when expressed as % ID/g. Accumulation of OX26 in the brain was higher in 15 postnatal (P)-day-old rats than in P0 and adult (P70) rats. Iron-deficiency did not increase OX26 uptake in P15 rats. Three attempts were made to investigate transport from BCECs further into the brain. (i) Using a brain capillary depletion technique, 6-9% of OX26 was identified in the post-capillary compartment consisting of brain parenchyma minus BCECs. (ii) In cisternal CSF, the volume of distribution of OX26 was higher than for Ni-IgG2a when corrected for plasma concentration. (iii) Immunohistochemical mapping revealed the presence of OX26 almost exclusively in BCECs; extravascular staining was observed only in neurons situated periventricularly. The data support the hypothesis of facilitated uptake of OX26 due to the presence of transferrin receptors at the blood-brain barrier (BBB). However, OX26 accumulation in the post-capillary compartment was too small to justify a conclusion of receptor-mediated transcytosis of OX26 occurring in BCECs. Accumulation of OX26 in the post-capillary component may result from a diphasic transport that involves high-affinity accumulation of OX26 by the BCECs, clearly exceeding that of Ni-IgG2a, followed by a second transport mechanism that releases OX26 non-specifically further into the brain. The periventricular localization suggests that OX26 probably also derives from transport across the blood-CSF barrier.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / cerebrospinal fluid
  • Antibodies, Monoclonal / metabolism*
  • Biological Transport
  • Blood-Brain Barrier*
  • Brain / blood supply
  • Brain / immunology
  • Capillaries / physiology
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid
  • Immunoglobulin G / metabolism
  • Immunohistochemistry
  • Iodine Radioisotopes
  • Iron Deficiencies
  • Kinetics
  • Mice
  • Rats
  • Rats, Wistar
  • Receptors, Transferrin / immunology*


  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Iodine Radioisotopes
  • Receptors, Transferrin