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

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Abstract
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 constituents of the endomembrane system within the choroid epithelium are summarized diagrammatically.

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