Abstract
As well as systemic vascular endothelial cells, the liver has specialised sinusoidal endothelial cells (LSEC). LSEC dysfunction has been documented in many diseased states yet their phenotype in normal human liver has not been comprehensively assessed. Our aim was to improve characterisation of subsets of endothelial cells and associated pericytes in the human liver. Immunofluorescence microscopy was performed on normal human liver tissue samples to assess endothelial and structural proteins in a minimum of three donors. LSEC are distributed in an acinar pattern and universally express CD36, but two distinctive subsets of LSEC can be identified in different acinar zones. Type 1 LSEC are CD36hiCD32−CD14−LYVE-1− and are located in acinar zone 1 of the lobule, while Type 2 LSEC are LYVE-1+CD32hiCD14+CD54+CD36mid-lo and are located in acinar zones 2 and 3 of the lobule. Portal tracts and central veins can be identified using markers for systemic vascular endothelia and pericytes, none of which are expressed by LSEC. In areas of low hydrostatic pressure LSEC are lined by stellate cells that express the pericyte marker CD146. Our findings identify distinctive populations of LSEC and distinguish these cells from adjacent stellate cells, systemic vasculature and pericytes in different zones of the liver acinus.
Highlights
As well as systemic vascular endothelial cells, the liver has specialised sinusoidal endothelial cells (LSEC)
Expression of CD36 in these Type 2 liver sinusoidal endothelial cells (LSEC) varies from moderate in Zone 2 (Z2) to low in Zone 3 (Z3) (Figs 2A,D, 3D and E) but is almost always lower than for Type 1 LSEC
In this paper we demonstrate heterogeneity of LSEC in normal human liver, identifying two LSEC types that are distinctly distributed in the liver acinus
Summary
As well as systemic vascular endothelial cells, the liver has specialised sinusoidal endothelial cells (LSEC). Portal tracts and central veins can be identified using markers for systemic vascular endothelia and pericytes, none of which are expressed by LSEC. Our findings identify distinctive populations of LSEC and distinguish these cells from adjacent stellate cells, systemic vasculature and pericytes in different zones of the liver acinus. The intention of this study was to define molecules differentially expressed by endothelial cells and pericytes in different zones of the human liver. Some electron microscopy studies revealed structural differences between periportal and pericentral LSEC, such as the size of LSEC membrane fenestrae[10,11]. Taken together, all these data suggested LSEC may be heterogeneous at the molecular level
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