Transcytosis of protein through the mammalian cerebral epithelium and endothelium. I. Choroid plexus and the blood-cerebrospinal fluid barrier. 1988

B J Balin, and R D Broadwell
Division of Neuropathology, University of Maryland School of Medicine, Baltimore 21201.

The potential for transcytosis (endocytosis----intracellular transport----exocytosis) of protein and membrane events associated with fluid phase and adsorptive endocytic processes within epithelia of the choroid plexus [blood-cerebrospinal fluid (CSF) barrier] were investigated in mice injected intravenously or into the lateral cerebral ventricle with native horseradish peroxidase (HRP) or the lectin wheatgerm agglutinin (WGA) conjugated to HRP. WGA binds to specific cell surface oligosaccharides and enters cells by the process of adsorptive endocytosis; native HRP is taken into cells non-specifically by fluid phase endocytosis. The lysosomal system of organelles and the endoplasmic reticulum, identified by enzyme cytochemical markers applied to choroid epithelia, were analysed for possible participation in transcytosis and compared to epithelial organelles harbouring the exogenous tracer proteins. Blood-borne native HRP was endocytosed readily by choroid epithelia whereas WGA-HRP was not, perhaps because WGA-HRP does not escape fenestrated endothelia as easily as native HRP. The blood-borne proteins incorporated within endocytic vesicles by choroid epithelia were directed to endosomes (prelysosomes) and secondary lysosomes (e.g. tubules, multivesicular/dense bodies) for eventual degradation and did not reach the apical/microvillus surface. Both CSF-borne native HRP and WGA-HRP entered choroid epithelia within endocytic vesicles derived from the microvillus border. Native HRP, ultimately sequestered within endosomes and secondary lysosomes, failed to undergo transcytosis through the epithelia into the basolateral clefts. Conversely, CSF-borne WGA-HRP was transported through the epithelia and released into the basolateral clefts within 10 min post-injection. The lectin conjugate labelled epithelial vesicles, endosomes, secondary lysosomes and, at 30 min post-injection, the transmost saccule of the Golgi complex which exhibits acid hydrolase activity. Tubular profiles, related either to the endosome apparatus or to the lysosomal system, and the endoplasmic reticulum did not appear involved in the transcytotic pathway. The data suggest that CSF-borne protein entering the choroid epithelium by adsorptive endocytosis can undergo rapid transcytosis through the cell. The results provide insight to transcytotic pathways utilizing vesicles, the endosomal apparatus, and the Golgi complex within the choroid epithelium for circumventing the blood-CSF barrier. Hypothesized membrane events and morphological associations among constitutents of the endomembrane system within the choroid epithelium are summarized diagrammatically.

UI MeSH Term Description Entries
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D002831 Choroid Plexus A villous structure of tangled masses of BLOOD VESSELS contained within the third, lateral, and fourth ventricles of the BRAIN. It regulates part of the production and composition of CEREBROSPINAL FLUID. Chorioid Plexus,Plexus Choroideus,Choroideus, Plexus,Plexus, Chorioid,Plexus, Choroid
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D004727 Endothelium A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body. Endotheliums
D004848 Epithelium The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body. Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D005089 Exocytosis Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.

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