Endothelial vesicles in the blood-brain barrier: Are they related to permeability?

1. Macromolecules cross capillary walls via large vascular pores that are t hought to be formed by plasmalemmal vesicles. Early hypotheses suggested th at vesicles transferred plasma constituents across the endothelial wall eit her by a "shuttle" mechanism or by fusing to form transient patent channels for diffusion. Recent evidence shows that the transcytotic pathway involve s both movement of vesicles within the cell and a series of fusions and fis sions of the vesicular and cellular membranes. 2. The transfer of macromolecules across the capillary wall is highly speci fic and is mediated by receptors incorporated into specific membrane domain s. Therefore, despite their morphological similarity, endothelial vesicles form heterogeneous populations in which the predominant receptor proteins i ncorporated in their membranes define the functions of individual vesicles. 3. Blood-brain barrier capillaries have very low permeabilities to most hyd rophilic molecules. Their low permeability to macromolecules has been presu med to be due to an inhibition of the transcytotic mechanism, resulting in a low density of endothelial vesicles. 4. A comparison of vesicular densities and protein permeabilities in a numb er of vascular beds shows only a very weak correlation, therefore vesicle n umbers alone cannot be used to predict permeability to macromolecules. 5. Blood-brain barrier capillaries are fully capable of transcytosing speci fic proteins, for example, insulin and transferrin, although the details ar e still somewhat controversial. 6. It has recently been shown that the albumin binding protein gp60 (also k nown as albondin), which facilitates the transcytosis of native albumin in other vascular beds, is virtually absent in brain capillaries. 7. It seems likely that the low blood-brain barrier permeability to macromo lecules may be due to a low level of expression of specific receptors, rath er than to an inhibition of the transcytosis mechanism.