Uptake ability of hepatic sinusoidal endothelial cells and enhancement by lipopolysaccharide

Abstract

The liver is one of the major organs that remove exogenous substances and waste products from the blood circulation. Hepatic macrophages (Kupffer cells) and sinusoidal endothelial cells are responsible for the scavenger function of the liver. The sinusoidal endothelial cells, called scavenger endothelial cells, are believed to take up only soluble substances and nanometer-sized particles under normal conditions, while Kupffer cells can ingest larger particles and whole cells. However, the sinusoidal endothelial cells may have the potential to take up considerably large particles under special conditions. In this morphological study, we compared the uptake ability between sinusoidal endothelial cells and Kupffer cells after intravenous injections of latex beads (20 nm, 100 nm and 500 nm in diameter), bovine serum albumin (BSA) and dextran. Under normal conditions, the sinusoidal endothelial cells vigorously took up 100-nm-sized latex beads as well as 20-nm latex beads. BSA and dextran were ingested by the endothelial cells but not the Kupffer cells. The administration of lipopolysaccharide (LPS), which mimics inflammation, stimulated the uptake by endothelial cells. The uptake of latex beads by Kupffer cells was also elevated under LPS-stimulated conditions, but the uptake of BSA and dextran by them was not. These findings suggest that the sinusoidal endothelial cells can ingest not only soluble substances but also larger particles than those expected, and their uptake ability is strengthened under inflammatory conditions.

Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice

“…KCs are labeled by injecting FITC-dyed beads, which are taken up by all phagocytic cell types in the liver ( 21 ). That the latex beads might also be taken up by liver sinusoidal endothelial cells (LSECs) is unlikely, because LSECs possess a maximum capacity of uptake for particles sized at ∼0.1 μm and have very low capacity for the uptake of particles ∼0.5 μm in diameter ( 35 ). In contrast, the capacity of KCs to ingest the larger particles is not decreased, even when the particle diameter increases much more ( 36 , 37 ), possibly up to the size of cells.…”

Hepatic Scavenger Receptor BI Protects Against Polymicrobial-induced Sepsis through Promoting LPS Clearance in Mice

“…These findings suggest that hepatic SR-BI is responsible for LPS removal and a defect in hepatic SR-BI-mediated LPS removal leads to endotoxemia, which likely accounts for exacerbated inflammatory cytokine production observed in Scarb1 I179N mice; These findings also imply that non-hepatic SR-BI may be required for the recruitment of LPS to circulation, and a deficiency of non-hepatic SR-BI leads to a delayed inflammatory response in the early stage of sepsis. Endothelial cells have been shown to uptake LPS in a receptordependent manner (72,73). Interestingly, earlier studies showed that endothelial cells express high levels of SR-BI (23,24,74).…”

Hepatic uptake and deacylation of the LPS in bloodborne LPS-lipoprotein complexes

“…Some of these studies used isolated SECs or hepatocytes that were exposed ex vivo to LPS; others found LPS associated with these cell types in vivo following intravenous LPS injection (3;9;10;13–15). In addition, LPS exposure can enhance the uptake of latex beads by SEC in situ , raising the possibility that these cells, if activated, might also take up LPS in vivo (16). In one indirect approach, FITC-LPS was injected intravenously and recovered from the bile within a few minutes (17); rapid transit through hepatocytes was suggested.…”