title: Transport of recombinant CD4 through the rat blood-brain barrier in vivo.
abstract: One class of potential acquired immunodeficiency syndrome therapeutics are derivatives of recombinant CD4 (rCD4). Therefore, the present investigations use in vivo techniques to measure the rate at which [3H]rCD4 is transported through the blood-brain barrier (BBB). In addition, the binding of labeled rCD4 to isolated human and bovine brain capillaries is measured. These studies show that [3H]CD4 is removed rapidly from the bloodstream with a half-time of 12.6 +/- 0.9 min. The volume of distribution (Vd) of the protein in brain increases with time and reaches a Vd that is 11.1 +/- 1.1-fold greater than the brain Vd of plasma marker, native rat serum albumin. In addition, [3H]rCD4 is extracted rapidly by the kidney and the ratio of rCD4 Vd to native rat serum albumin Vd in the rat kidney reaches 99 +/- 5 at 60 min after i.v. injection. rCD4 is shown to undergo transcytosis through the BBB using an internal carotid artery perfusion/capillary depletion method coupled with gel filtration fast protein liquid chromatography. In conclusion, these studies report the unexpected finding that rCD4 is transportable through the BBB. rCD4 is a cationic protein and the mechanism of rCD4 transport through the BBB may be analogous to the absorptive-mediated transcytosis of other polycationic proteins.
authors.affiliation: Department of Medicine, University of California Los Angeles School of Medicine.
authors.forename: W M
authors.initials: WM
authors.lastname: Pardridge
authors.forename: J L
authors.initials: JL
authors.lastname: Buciak
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects*; D015704:CD4 Antigens / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D015704:CD4 Antigens; D011994:Recombinant Proteins