Restricted transport of anti-transferrin receptor antibody (OX26) through the blood-brain barrier in the rat.
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.
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Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. T.Moos@mai.ku.dk
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D000375:Aging; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000276:immunology; D002196:Capillaries / Q000502:physiology; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D000090463:Iron Deficiencies; D007700:Kinetics; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D011990:Receptors, Transferrin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011990:Receptors, Transferrin