Morphological and cytochemical aspects of capillary permeability

Abstract

Transport of plasma soluble constituents across the capillary wall is of primordial importance in cardiovascular physiology. While physiological experiments have concluded with the existence of two sets of pores, a large one responsible for the transport of proteins and a small one designed for the diffusion of small solutes, the morphological counterparts have yet to get general agreement. In this review, we present the different proposed paths within and between the endothelial cells that do allow passage of plasma constituents and may respond to the definitions established by physiological means. The vesicular system existing in endothelial cells has been the first transendothelial path to be proposed. Several data have demonstrated the involvement of this system in transport, although others have systematically brought controversy. One alternative to the vesicles has been the demonstration of membrane-bound tubules creating, in certain cases, transendothelial channels that would allow diffusion of plasma proteins and other constituents across the capillary wall. Access to this tubulo-vesicular system could be restrained by the stomatal diaphragm and facilitated by specific membrane receptors. Further, we have demonstrated for the first time with morpho-cytochemical tools, that the intercellular clefts are the site of diffusion for small molecules such as peptides having a molecular weight inferior to 3,000. For the fenestrated capillary bed, we have shown that fenestrae are the site through which plasma constituents cross the capillary wall. However, and in spite of the existence of these large open pores, the endothelial cells still display the tubulo-vesicular system involved in transport of large molecules and their intercellular clefts are also the site of diffusion of small molecules. Making consensus on the existence of an intracellular tubulo-vesicular system in non-fenestrated capillaries, responsible for the transport of large molecules by the endothelial cells, and understanding the rational for the fenestrated capillary to have three paths for transport--the fenestrae, the tubulo-vesicular system, and the inter-endothelial clefts--require further investigation.

Morpho-functional studies of the blood-brain barrier in streptozotocin-induced diabetic rats

“…Another interesting result concerns the asymmetry between the luminal and the abluminal distributions of plasmalemmal vesicles in endothelial cells. Such asymmetry was already reported in the brain [53] as well as in other tissues [53,54,55,56] and raises concern with regards to the vesicular transcytotic models of endothelial transport. Cellular mechanisms regulating capillary wall permeability remain an ongoing debate and several paths such as the shuttling of vesicles, the existence of patent transendothelial channels and the inter-endothelial clefts have been proposed for the passage of molecules [42,56,57,58].…”

“…Such asymmetry was already reported in the brain [53] as well as in other tissues [53,54,55,56] and raises concern with regards to the vesicular transcytotic models of endothelial transport. Cellular mechanisms regulating capillary wall permeability remain an ongoing debate and several paths such as the shuttling of vesicles, the existence of patent transendothelial channels and the inter-endothelial clefts have been proposed for the passage of molecules [42,56,57,58]. Other endothelial structures, such as the vesicular-vacuolar organelles [59] and vesiculo-tubular systems [56,57] were reported to be involved in the transendothelial transport of serum proteins.…”

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

“…For endothelia of several organs of the body, experimental evidence points to the existence of what has been referred to as two sets of physiological pores: large pores responsible for the transport of proteins and small pores designed for the diffusion of small solutes. Opinions differ widely concerning which features of endothelial cells found in these organsfenestrae, the transtubulovesicular system including caveolae, and interendothelial clefts-are the morphological correlates to the two pore system suggested by the physiological data (Predescu et al, 1997;Michel and Curry, 1999;Silverstein, 1999;Smart et al, 1999;Galbiati et al, 2001;Bendayan, 2002;Feng et al, 2002;Simionescu et al, 2002).…”

“…An insidious problem with the use of dextrans is that they may interact with vessel walls and change the functional properties of the endothelium or cause changes in blood viscosity (Gustafsson et al, 1981;Pearson and Lipowsky, 2000;Bendayan, 2002;Gonzalez-Castillo et al, 2003;Tsai et al, 2003). Specifically, dextrans can bind irreversibly to the coronary vessel lumen in a mass-dependent manner and modulate coronary blood flow (GonzalezCastillo et al, 2003).…”

PV1 Is a Key Structural Component for the Formation of the Stomatal and Fenestral Diaphragms

“…Judged by its magnitude and importance for the underlying tissues, a critical function of the endothelium is to mediate the fluid and solute exchanges between the blood plasma and the interstitial fluid, in short microvascular permeability. Although the molecular mechanisms underlying this function are still largely unknown, several endothelial specialized subcellular structures have been involved in these processes: caveolae, transendothelial channels (TEC), fenestrae, sinusoidal gaps, vesiculo-vacuolar organelles (VVOs), and intercellular junctions (for reviews see Palade, 1991;Michel and Curry, 1999;Dvorak and Feng, 2001;Bendayan, 2002;Stan, 2002).…”