The Liver Sieve: Considerations Concerning the Structure and Function of Endothelial Fenestrae, the Sinusoidal Wall and the Space of Disse

Abstract

Sinusoids in the liver lobule ( Figure 1) are invested with a unique type of endothelial lining (Figure 2) consisting of endothelial cells with flattened processes perforated by small fenestrae of about 0.1 pm in size ( Figure 3). The open fenestrae lack a diaphragm and are arranged in groups to which the name "sieve plates" was given (1). A basal lamina is lacking and for that reason the fenestrae constitute an open connection between the sinusoidal lumen and the space of Disse. It is thought that the major part of the transport and exchange of fluid, solutes and particles between the blood and the space of Disse occurs through these open fenestrae. As a result, obvious filtration effects can be expected when particles of about the size of the fenestrae arrive in the liver. Another unique feature of liver sinusoidal endothelial cells is the high endocytotic capacity, which, together with the fenestrae and the absence of a basal lamina, makes them unique in the body (2). To the best of our knowledge, this particular type of endothelial cell is not found in any other organ. The distinction between endothelial cells and three other types of sinusoidal cells, i.e., Kupffer, fat-storing and pit cells, has repeatedly been described and reviewed (3, 4).Fenestrae were first observed following perfusion fixation (1); fixation is highly critical in the preservation and visualization of endothelial fenestrae, and this is valid for the sinusoidal area as a whole. No sophisticated apparatus is ileeded for perfusion fixation of the liver, but successful perfusion fixation is critically dependent on fast and well-dosed anesthesia of relatively stress-free

Persistent gene expression in rat liver in vivo by repetitive transfections using HVJ-liposome

“…The diameter of the fenestrae is reported to be about 175 nm in the periportal area. 15 Enlargement of fenestrae diameter has been reported after perfusion with pressure. 16 Although HVJ-liposome is about 400 nm in diameter, 17 the enlargement of fenestrae may contribute to the admission of HVJ-liposome to the parenchymal cells in our method.…”

Hydroporation as the mechanism of hydrodynamic delivery

“…15 The other 6-8% consists of pores with an average diameter of 100 nm. 16 These pores, referred to as the liver fenestrae, appear to be too small to allow large molecules like plasmid DNA to pass through. Therefore, the liver endothelium, although being porous, serves as a physical barrier for delivery of large molecules to the hepatocytes.…”

Influence of kavain on hepatic ultrastructure

“…Tissue samples were prepared according to standard protocols [19,20] . Briefly, glutaraldehyde perfused-fixed samples were cut into 1 mm 3 blocks in 1.5% glutaraldehyde/0.12 mol/L cacodylate buffer at pH 6.9.…”