Scavenger receptor B1, the HDL receptor, is expressed abundantly in liver sinusoidal endothelial cells

Abstract

Cholesterol from peripheral tissue, carried by HDL, is metabolized in the liver after uptake by the HDL receptor, SR-B1. Hepatocytes have long been considered the only liver cells expressing SR-B1; however, in this study we describe two disparate immunofluorescence (IF) experiments that suggest otherwise. Using high-resolution confocal microscopy employing ultrathin (120 nm) sections of mouse liver, improving z-axis resolution, we identified the liver sinusoidal endothelial cells (LSEC), marked by FcγRIIb, as the cell within the liver expressing abundant SR-B1. In contrast, the hepatocyte, identified with β-catenin, expressed considerably weaker levels, although optical resolution of SR-B1 was inadequate. Thus, we moved to a different IF strategy, first separating dissociated liver cells by gradient centrifugation into two portions, hepatocytes (parenchymal cells) and LSEC (non-parenchymal cells). Characterizing both portions for the cellular expression of SR-B1 by flow cytometry, we found that LSEC expressed considerable amounts of SR-B1 while in hepatocytes SR-B1 expression was barely perceptible. Assessing mRNA of SR-B1 by real time PCR we found messenger expression in LSEC to be about 5 times higher than in hepatocytes.

<b>A novel role for scavenger receptor B1 as a contributor to the capture of specific volatile odorants in the nasal </b><b>cavity </b>

“…6A). The pattern of staining was comparable to that obtained by Ganesan and co-workers using anti-SR-B1 antibodies other than TA301489 (8). Based on these results, we concluded that antibody TA301489 could satisfactorily demonstrate receptor localisation.…”

“…Immunoreactivity was found mostly along the outline of cavities, and was thought to arise from sinusoidal endothelial cells (Fig. 6A) (8). The signals were less evident on the cell surface of hepatic parenchymal cells (Fig.…”

Blood-Borne Lipopolysaccharide Is Rapidly Eliminated by Liver Sinusoidal Endothelial Cells via High-Density Lipoprotein

“…It has been suggested that hepatocyte and macrophage SR-B1 play a role by either clearing or responding to LPS(49). However, we have recently demonstrated that in liver, HDL receptor SR-B1 is expressed abundantly in LSEC but is barely perceptible on hepatocytes(17). These findings offer an irresistible clue that SR-B1 in LSEC plays a role in inflammation by eliminating LPS.…”

“…We recently discovered the scavenging abilities of LSEC, possessing high endocytic ability, take up particles less than 200nm in diameter, such as blood borne viruses or small immune complexes(14,15). LSEC are well equipped for endocytosis, given that they express major endocytic receptors including those for mannose, collagen, hyaluron, L-SIGN, FcγRIIb and, most importantly, several types of scavenger receptors(16,17). Thus, whereas particles under 200 nm are eliminated from blood by the endocytosis function of LSEC, uptake and clearance of larger particles, such as bacteria or cells, requires the phagocytic action of macrophages.…”

Mouse Liver Sinusoidal Endothelium Eliminates HIV-Like Particles from Blood at a Rate of 100 Million per Minute by a Second-Order Kinetic Process

“…It is also possible that the binding site on LSEC is a dimer, although we know of no evidence that CD4 or L-SIGN, both known to be expressed on LSEC (13, 14), dimerize. However, there is precedence for LSEC to express dimeric receptors; i.e., SRB-1, a receptor for HDL and HCV envelope protein E2 expressed on LSEC (6, 7, 15), is known to dimerize and oligomerize (16). What precisely second order means in the case of our Figure 1 data awaits additional study.…”