Table 3 Classification of sinusoidal reticuloendothelial blood capillary microvasculature

•Endothelial cells w/high levels of phago-endocytosis[130, 131] •Basement membrane commonly absent[64, 77, 203] •Patchy anionic glycocalyx of sialyated glycoproteins at non-endocytic sites[132–134] deficient in hyaluronan[137–140]

Open fenestrae

•Diameters of open fenestrae variable across mammalian species: 1)human & rabbit: avg. diameter ~105 nm (range 50 to 180 nm) [17, 83]

2) mouse & rat: avg. diameter ~135 nm (range 50 to 280 nm) [16, 83]

•Absence of basement membrane underlying fenestrae and lack of glycocalyx matrix fibers within fenestrae [204]

•Phago-endocytic phenotype of endothelial cells [205–207]

•Absence of basement membrane underlying fenestral openings and relative lack of glycocalyx matrix fibers in the vicinity of the fenestral openings renders fenestrae permeable to macromolecules as large as the diameters of the fenestrae themselves [16, 17]

•Open fenestrae constitute the transvascular pathway for the passage of macromolecules into the interstitial hepatic Space of Disse

•Phago-endocytosis and release of non-endogenous macromolecules into the hepatic interstitium [141]

•Wide size range of nanoparticles [136, 208–210]*

Interendothelial junctions

•Endothelial cells non-fenestrated except during transcellular passage of blood cells across endothelial cell membrane when cells transiently fenestrated [40–42]

•Macula occludens interendothelial junctions [42–44]

•Phago-endocytic phenotype of endothelial cells [45, 46, 211]

•Transvascular flow of macromolecules smaller than ~5 nm into the bone marrow interstitial space across maculae occludens interendothelial junctions

• Phago-endocytosis and release of non-endogenous macromolecules into bone marrow interstitium [34, 35]

•Narrow size range of nanoparticles [36–38]**