ADS CAS PubMed Article Google Scholar The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We quantify the association between immunoliposomes and brain capillary endothelial cells (BCECs) and their transport across these cells using flow cytometry and platinum content quantification in a primary rat in vitro model of the BBB. By Takeshi Kawamoto. Efficient gene delivery targeted to the brain using a ... The expression of transferrin receptor is known to be ubiquitous, although the expression level is comparatively higher in brain capillary endothelial cells. 1984 Nov 8; 312 (5990):162–163. Because it is known that in PV-sensitive cells, the association In Vivo Labeling of Brain Capillary Endothelial Cells ... The nanoparticles move unobstructed within endothelium, but transcytosis-mediated brain entry occurs mainly at post-capillary venules, and is negligible in capillaries. The vascular location of nanoparticle brain entry corresponds to the presence of perivascular space, which facilitates nanoparticle movement after transcytosis. PURPOSE: The expression level of the transferrin receptor (TfR) on brain capillary endothelial cells (BCECs) and the endocytosis of 125I-transferrin (125I-Tf) by this receptor was investigated. PV clearly interacted with mTfR1 proteins in vitro ( FIGURE 1., FIGURE 2.) The transferrin receptor (TfR) is related to a transcytosis process in these cells, and the 8D3 monoclonal antibody (mAb), directed against the mouse TfR, is able to induce a … Proc Natl Acad Sci U S A. Transferrin receptor on endothelium of brain capillaries. Using a brain perfusion technique in rats, we have shown a significant brain capillary uptake of circulating transferrin (Tf)-bound and free 59 Fe (1 nM) at rates of 136 ± 26 and 182 ± 23 μL/g/min, respectively, while their respective transport rates into brain parenchyma were 1.68 ± 0.56 and 1.52 ± 0.48 μL/g/min. in this study, and we found that VP1 is responsible for this binding ( Fig. Nature 312 , 162–163 (1984). Transferrin receptor on endothelium of brain capillaries. The transferrin receptor is abundantly expressed in cancer cells and endothelial cells of the brain capillaries, as well as the choroid plexus and neurons that recognize different isoforms of transferrin for the transportation of iron into the brain. Transferrin receptor-targeting increases the uptake of an encapsulated cargo into brain capillary endothelial cells, but does not improve transendothelial transport in vitro To provide nutrients for these cells, transport mechanisms must exist and indeed have been demonstrated for metabolites 1 . Many of these approaches base their brain accumulation strategies on targeting of the transferrin receptor 4. The transferrin receptor is responsible for the transport of iron into the brain parenchyma to maintain iron homeostasis that is of great importance for metabolism, neural conductivity, and hence, proper brain function 5. Using a brain perfusion technique in rats, we have shown a significant brain capillary uptake of circulating transferrin (Tf)‐bound and free 59 Fe (1 n m) at rates of 136 ± 26 and 182 ± 23 μL/g/min, respectively, while their respective transport rates into brain parenchyma were 1.68 ± 0.56 and 1.52 ± 0.48 μL/g/min. Subsequent steps are less clear. The transferrin receptor (TfR) has been suggested to ferry drug compounds across the blood-brain barrier. Anti-transferrin Receptor Monoclonal Antibody-Colloidal Gold Conjugate in Brain Capillary Endothelium’ ULRICH BICKEL,’ YOUNG-SOOK KANG, TAKAYOSHI YOSHIKAWA, and WILLIAM M. PARDRIDGE Department of Medicine and Brain Research InstitUte, UCLA School of Medicine, Los Angeles, Cahfirnia. Furthermore, the influence of iron, the iron scavenger deferoxamine mesylate (DFO), astrocytic factors, a GTP-ase inhibitor (tyrphostin-A8, T8), lipopolysaccharide (LPS), and the radical … Intravenous injection of Ri7 or 8D3 MAb coupled with AF750 led to … Purpose: The expression level of the transferrin receptor (TfR) on brain capillary endothelial cells (BCECs) and the endocytosis of 125I-transferrin (125I-Tf) by this receptor was investigated. We now show that monoclonal antibodies against rat and human transferrin receptors label … the transferrin receptor, we generated mouse brain capillary endothelial cell line (MBEC4) expressing FLAG-mTfR1. receptor-mediated transcellular transport system of the brain capillary endothelial cells (BCECs). • Cultured endothelial cells express the TfR at both the mRNA and protein level. The tumors studied included 10 glioblastomas multiforme (GBM's), nine other glial tumors, and … Receptors expressed on the BBB, including transferrin (Tf) receptor and insulin receptor, have been used for brain-targeting drug delivery research . Regional Tf receptor density (B max) in brain endothelium … Recently, we have shown that transferrin (Tf) is actively endocytosed by the Tf R on primary cultured bovine brain capillary endothelial cells (BCEC). The Tf receptor is of particular interest because its expression in capillaries throughout the body is restricted to brain capillaries ( 10 ). Jefferies, W. A. et al. Recently, we have shown that transferrin (Tf) is actively endocytosed by the Tf R on primary cultured bovine brain capillary endothelial cells (BCEC). Receptor-mediated transcytosis of the transferrin receptor has been suggested as a potential transport system to deliver therapeutic molecules into the brain. Brain capillary endothelial cells (BCECs) express transferrin receptors. The transcytosis of a receptor-specific MAb Trojan horse through the BBB is a multi-step process that involves binding of the MAb to the targeted receptor on the luminal membrane of the brain capillary endothelium. Using a brain perfusion technique in rats, we have shown a significant brain capillary uptake of circulating transferrin (Tf)-bound and free 59 Fe (1 nM) at rates of 136 ± 26 and 182 ± 23 μL/g/min, respectively, while their respective transport rates into brain parenchyma were 1.68 ± 0.56 and 1.52 ± 0.48 μL/g/min. The transferrin receptor is an interesting and unique target, since it is exclusively expressed on the endothelial cells of the brain capillaries and not on … Characterization and modulation of the transferrin receptor on brain capillary endothelial cells. Endothelium of the cerebral blood vessels, which constitute the blood–brain barrier, strictly controls adhesion and trafficking of leukocytes into the brain. 1991 Jun 1; 88 (11):4771–4775. The objectives of the present study were to investigate whether the expression of transferrin receptor 1 (TfR1), glucose transporter 1 (Glut1), or Cluster of Differentiation 98 Heavy Chain (CD98hc) is epigenetically regulated in brain capillary endothelial cells (BCECs) denoting the blood-brain barrier (BBB). The TfR is expressed on endothelial cells of the brain capillaries where it is involved in iron transport to the bra in via receptor-mediated endocytosis of transferrin (Tf) (10). PV interacts with the apical domain of mTfR1 on mouse brain capillary endothelial cells (MBEC4) in a dose-dependent manner via its capsid protein (VP1). Secondly, the mechanism of endocytosis was investigated. As a possible route for invasion of the CNS, circulating poliovirus (PV) in the blood is believed to traverse the blood-brain barrier (BBB), resulting… If this PV permeation is a specific event in the BBB, the existence of additional molecules that are expressed only in brain capillary endothelial cells is plausible. [PMC free article] Jefferies WA, Brandon MR, Hunt SV, Williams AF, Gatter KC, Mason DY. We now show that monoclonal antibodies against rat and human transferrin receptors label blood capillaries in the brain but not in other tissues. Brain capillary endothelial cells (BCECs) express transferrin receptors. The expression level of the transferrin receptor (TfR) on brain capillary endothelial cells (BCECs) and the endocytosis of 125 I-transferrin (125 I-Tf) by this receptor was investigated. Download Download PDF. Nature. The blood/brain barrier prevents the passive diffusion of proteins and metabolites from cerebral blood vessels into tissue spaces around neuronal and glial cells. The transferrin receptor is abundantly expressed in cancer cells and endothelial cells of the brain capillaries, as well as the choroid plexus and neurons that recognize different isoforms of transferrin for the transportation of iron into the brain. In the rat this labelling occurs after injection of antibody into the blood, thus the receptors seem to be accessible at the endothelial surface. PURPOSE: The expression level of the transferrin receptor (TfR) on brain capillary endothelial cells (BCECs) and the endocytosis of 125I-transferrin (125I-Tf) by this receptor was investigated. The uptake of a potential drug vector (OX26, or anti—transferrin receptor antibody IgG2a) conjugated to polyethyleneglycol-coated liposomes by BCECs was studied using in situ perfusion in 18-day-old rats in which the uptake of OX26 is almost twice as high as in the adult rat. ), transferrin receptor is a plausible candidate for the receptor of PV permeation of the brain. The expression of transferrin receptor is known to be ubiquitous, although the expression level is comparatively higher in brain capillary endothelial cells. Coincident expression and distribution of melanotransferrin and transferrin receptor in human brain capillary endothelium. The iron then dissociates from transferrin in endosomal compartments and is transcytosed by unknown mechanisms, while the transferrin is retroendocytosed. Expression of membrane-bound transferrin-like protein p97 on the cell surface of chondrocytes. Transferrin receptor on endothelium of brain capillaries. Brain Research, 1996. Avidin / biotin / peroxidase reaction of isolated human brain capillaries with a mouse monoclonal antibody to the human transferrin receptor (a mouse IgG, subtype) (AL or with a … We have examined the ability of a monoclonal antibody (OX-26), which recognizes the rat transferrin receptor, to function as a carrier for the delivery of drugs across the blood-brain barrier. The uptake of a potential drug vector (OX26, or anti-transferrin receptor antibody IgG2a) conjugated to polyethyleneglycol-coated liposomes by BCECs was studied using in situ perfusion in 18-day-old rats in which the uptake of OX26 is almost twice as high as in the adult rat. The distribution of transferrin receptor (TfR) in normal human brain-tissue obtained at autopsy and in brain-tumor biopsy specimens from 27 patients was determined by immunohistochemistry using two specific murine monoclonal antibodies against human TfR. If this PV permeation is a specific event in the BBB, the existence of additional molecules that are expressed only in brain capillary endothelial cells is plausible. • TfR expression and function is studied in cultured brain capillary endothelial cells. Binding experiments showed that BBCECs express 35,000 high-affinity (concn at 50% recep … The BBB regulates molecular flux to maintain an optimal environment for neuronal function and protects the brain from toxins and pathogens. MAbs were fluorolabeled with either Alexa Fluor (AF) dyes 647 or 750. Methods In the rat this labelling occurs after injection of antibody into the blood, thus the receptors seem to be accessible at the endothelial surface. Transferrin receptors are glycoproteins in nature, consisting of two subunits (90 kDa) with a disulfide linkage. The objective of this investigation is to determine whether the Tf R can facilitate endocytosis of a (protein) model drug, using Tf as a targeting vector. This complex then undergoes receptor-mediated endocytosis into the intracellular compartment of the endothelium, followed by Brain capillary endothelial cells (BCECs) express transferrin receptors. Scopus (789) Google Scholar. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. Here, we have characterized the brain distribution of two monoclonal antibodies (MAbs) targeting the mouse transferrin receptor (TfR) (clones Ri7 and 8D3) compared with control IgGs after intravenous injection into mice. Using radio-labeling, the uptake of … This antibody, which was … Transferrin receptor on endothelium of brain capillaries | Nature. P h arm Res 21 (5): 761-769 Validation of the TfR for drug targeting Delivery of nonlipophilic drugs to the brain is hindered by the tightly apposed capillary endothelial cells that make up the blood-brain barrier. The TfR is expressed on endothelial cells of the brain capillaries where it is involved in iron transport to the bra in via receptor-mediated endocytosis of transferrin (Tf) (10). The uptake of a potential drug vector (OX26, or anti—transferrin receptor antibody IgG2a) conjugated to polyethyleneglycol-coated liposomes by BCECs was studied using in situ perfusion in 18-day-old rats in which the uptake of OX26 is almost twice as high as in the adult rat. We now show that monoclonal antibodies against rat and human transferrin receptors label blood capillaries in the brain but not in other tissues. Because of the poten as non-inflammatory BBB-penetrating nano vehicles.45 tial for medicinal products throughout BBB, graphene Over brain capillaries, surface transferrin receptors quantum dots (GQDs) are among those carbon-based (TfR) are a popular strategy for brain-targeting. A cell culture model of the blood-brain barrier consisting of a coculture of bovine brain capillary endothelial cells (BBCECs) and astrocytes has been used to examine the mechanism of iron transport to the brain. Brain capillary endothelial cells (BCECs) express transferrin receptors. 2a, lane f) or of transferrin receptors (not shown) did not affect ICAM-1-induced cortactin phosphorylation. demonstration of transferrin receptors on brain capillary endothelial cells (BCECs) more than 20 years ago provided the evidence for the now accepted view that the first step in blood to brain transport of iron is receptor-mediated endo-cytosis of transferrin. The evidence supports an iron transport model in which iron-loaded transferrin is taken up by receptor-mediated endocytosis at the luminal membrane of brain capillaries. The objectives of the present study were to investigate whether the expression of transferrin receptor 1 (TfR1), glucose transporter 1 (Glut1), or Cluster of Differentiation 98 Heavy Chain (CD98hc) is epigenetically regulated in brain capillary endothelial cells (BCECs) denoting the blood-brain barrier (BBB). And function is studied in cultured brain capillary endothelial cells express the at. Expression of membrane-bound transferrin-like protein p97 on the cell surface of chondrocytes delivering immunoliposomes and their cargo. And glial cells prevents the passive diffusion of proteins and metabolites from cerebral blood vessels into spaces. With mTfR1 proteins in vitro ( FIGURE 1., FIGURE 2. antibody and antibody-drug... /a., Mason DY these cells, transport mechanisms must exist and indeed have been demonstrated for.... 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