Structural aspects of the permeability of the microvascular endothelium

This article reviews recent findings and current views concerning the structural aspects of microvascular permeability. The vascular endothelium is considered as a simple squamous epithelium which has acquired a remarkably high permeability to water and water soluble solutes (including macromolecules) through a characteristic process of differentiation of its cells. In terms of cellular structures, this differentiation involves an unusually large population of plasmalemmal vesicles. The evidence so far obtained indicates that these vesicles function as (1) mass-carriers of fluid and solutes across the endothelium and as (2) generators of transendothelial channels by concomitant fusion (followed by fission) with both domains (luminal and tissular) of the plasmalemma. The endothelial fenestrae of visceral capillaries are initially transendothelial channels subsequently collapsed to minimal length. The intercellular junctions of the endothelium are not detectably permeable to tracers of diam. greater than or equal to 18--20 A in capillaries, but are focally open to probes of 50--60 A diam. in postcapillary (pericytic) venules. A correlation is attempted between transendothelial channels (and fenestrae) and the pore systems postulated by the pore theory of capillary permeability. The channels appear to function as either small or large pores depending on the porosity of their associated diaphragms and on the size of local strictures along their pathway. Two main components are recognized in the analysis of capillary permeability: 1) a basic component comparable to that of other simple epithelia and involving transport across the plasmalemma and probably along the intercellular junctions (for molecules of diam. greater than or equal to 10 A); and a differentiated component which involves plasmalemmal vesicles and their derivatives (transendothelial channels and fenestrae). The postulated pores of the capillary endothelium are part of this differentiated component. The special situation found in postcapillary venules (focally open junctions) seems to be related to the role played by these vessels in inflammatory reactions.