How Plasma Macromolecules Cross the Endothelium

Simionescu, Maya; Ghitescu, Lucian; Fixman, A; Simiónescu, N

doi:10.1152/physiologyonline.1987.2.3.97

Cited by 20 publications

(29 citation statements)

References 6 publications

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“…This pathway is reported for the receptor-mediated transcytosis of gold-labeled albumin in peripheral endothelial cells (41). Analyses of cerebral and noncerebral endothelia in which the luminal and abluminal plasma membranes appear attenuated suggest that a coalescence of vesicles may form transendothelial channels through which blood-borne molecules can pass unobstructed (8,41). Endosomes serving as an intermediary in the transcellular vesicular transport of ligands (Fig.…”

Section: Discussionmentioning

confidence: 63%

Transcytotic pathway for blood-borne protein through the blood-brain barrier.

Broadwell

Balin

Salcman

1988

Proc. Natl. Acad. Sci. U.S.A.

163

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The transcytosis of blood-borne protein through the blood-brain barrier, a consequence of recruitment of the Golgi complex within nonfenestrated cerebral endothelia, was identified in mice and rats ih'ected intravenously with the lectin wheat germ agglutinin (WGA) coijugated to the enzymatic tracer horseradish peroxidase (EIRP). WGA enters cells by adsorptive endocytosis after binding to specific cell surface oligosaccharides. Blood-borne WGA-HRP labeled the entire cerebrovascular tree from the luminal side 5 min after injection; pericytes, located on the abluminal surface of cerebral endothelia, sequestered the lectin conjugate 6 hr later. Endothelial organelles harboring WGA-HRP 3 hr after injection included the luminal plasmalemma, endocytic vesicles, endosomes (prelysosomes), secondary lysosomes, and the Golgi complex. The peroxidase reaction product labeled the abluminal surface of cerebral endothelia and occupied the perivascular clefts by 6 hr. Within 12 hr, organelles labeled with WGA-HRP in pericytes were identical to those observed in endothelia. Blood-borne native HIRP, entering cells by bulk-phase endocytosis, was neither, directed to the Golgi complex nor transferred across nonfenestrated cerebral endothelia. The results suggest that blood-borne molecules taken into the cerebral endothelium by adsorptive endocytosis and conveyed to the Golgi complex can, either by themselves or as vehicles for other molecules excluded from the brain, undergo transcytosis through the blood-brain barrier without compromising the integrity of the barrier.Evidence for the transcytosis (endocytosis to intracellular transport to exocytosis) of blood-borne protein through nonfenestrated cerebral endothelia (blood-brain barrier) is largely morphological and is based on application of the probe molecule native horseradish peroxidase (HRP); native HRP enters cells indiscriminately by fluid or bulk-phase endocytosis. Studies employing HRP suggest that transendothelial vesicular transport of the protein occurs normally from blood to brain through segments of specific arterioles (1) and from brain to blood through capillaries (2, 3). Other investigations propose that transcytosis of blood-borne peroxidase through cerebral capillaries is induced experimentally (4-7). The fusion of intraendothelial vesicles to form patent transendothelial channels is documented for fenestrated endothelia in circumventricular organs (8); however, existence of similar channels within the blood-brain barrier endothelia is equivocal (9).Our investigations of the mammalian blood-brain barrier have emphasized that blood-borne native HRP with internalized endothelial surface membrane is directed to endosomes (a prelysosomal compartment) and to secondary lysosomes for eventual degradation without undergoing transendothelial transport (9-13). Protein tracers exposed to the abluminal surface of the cerebral endothelium by way of the blood through the meninges in the mouse, by ruptured interendothelial tight junctions, or by ventriculo-cisternal perf...

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Section: Discussionmentioning

confidence: 63%

Transcytotic pathway for blood-borne protein through the blood-brain barrier.

Broadwell

Balin

Salcman

1988

Proc. Natl. Acad. Sci. U.S.A.

163

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“…Having caveolae may be especially relevant in tissues that undergo a high degree of stretch such as the lung and heart. Morphological studies show that the endothelium within these tissues contains a large population of caveolae (48). Caveolae may have a special role, perhaps by being more or less sensitive to particular types of forces that prevail in these tissues.…”

Section: Figmentioning

confidence: 99%

Rapid Mechanotransduction in Situ at the Luminal Cell Surface of Vascular Endothelium and Its Caveolae

Rizzo

Sung

et al. 1998

Journal of Biological Chemistry

165

145

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“…visual tracking of the particles as they eventually cross the vessel wall (Milici et al 1987;Simionescu et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural study on the interaction of native and cationized albumin-gold complexes with mouse brain microvascular endothelium

1996

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The main objective of this ultrastructural study was to gain insights into the cellular mechanisms responsible for the enhanced brain uptake of blood-borne cationized albumin observed by several authors utilizing quantitative methodology. Mice were injected intravenously or into the common carotid artery (in vivo experiments) or perfused in situ with solutions of native or cationized bovine serum albumin complexed with colloidal gold (BSA-G or cBSA-G respectively). The results indicate that: (1) the main drawbacks of in vivo experiments are very intense phagocytosis of the tracer particles by Kupffer cells located in the liver sinusoids and also escape of the tracer through capillaries of skeletal and heart muscles. This results in a rapid decline of the concentration and disappearance of the circulating tracer particles; (2) BSA-G and cBSA-G both in vivo (up to 30 min circulation) or after perfusion in situ (up to 15 min) do not cross the wall of brain microvessels representing the blood-brain barrier; (3) enhanced entrance of cationized albumin into the brain occurs through fenestrated endothelium of the capillaries located in the examined circumventricular organs (median eminence and neurohypophysis). Although BSA-G is also transported by these fenestrated capillaries, this process is evidently less intense than in the case of cBSA-G; (4) the enhanced passage of cBSA-G across fenestrated capillaries occurs mainly via vesicular transport (adsorptive transcytosis), through transendothelial channels and eventually through interendothelial junctional clefts; (5) the fenestrated capillaries of the choroid plexus appear to be less permeable for both tracers than those located in the other circumventricular organs.

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How Plasma Macromolecules Cross the Endothelium

Cited by 20 publications

References 6 publications

Transcytotic pathway for blood-borne protein through the blood-brain barrier.

Transcytotic pathway for blood-borne protein through the blood-brain barrier.

Rapid Mechanotransduction in Situ at the Luminal Cell Surface of Vascular Endothelium and Its Caveolae

Ultrastructural study on the interaction of native and cationized albumin-gold complexes with mouse brain microvascular endothelium

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