Fc receptor mediated endocytosis of small soluble immunoglobulin G immune complexes in Kupffer and endothelial cells from rat liver

2000 ◽  
Vol 113 (18) ◽  
pp. 3255-3266
Author(s):  
T. Lovdal ◽  
E. Andersen ◽  
A. Brech ◽  
T. Berg
Keyword(s):  
Endothelial Cells ◽  
Kupffer Cells ◽  
Immune Complexes ◽  
Scavenger Receptor ◽  
Mannose Receptor ◽  
Endocytic Pathway ◽  
Scavenger Receptors ◽  
Receptor Ligands ◽  
Receptor Ligand ◽  
Liver Endothelial Cells

Soluble circulating immunoglobulin G immune complexes are mainly eliminated by the liver, predominantly by uptake in the Kupffer cells, but also the liver endothelial cells seem to be of importance. In the present study we have followed the intracellular turnover of immune complexes after Fc(gamma) receptor mediated endocytosis in cultured rat liver endothelial cells and Kupffer cells by means of isopycnic centrifugation, DAB cross-linking and morphological techniques. For the biochemical experiments the antigen, dinitrophenylated bovine serum albumin (BSA), was labeled with radioiodinated tyramine cellobiose that cannot cross biological membranes and therefore traps labeled degradation products at the site of formation. The endocytic pathway followed by immune complexes was compared with that followed by scavenger receptor ligands, such as formaldehyde treated BSA and dinitrophenylated BSA, and the mannose receptor ligand ovalbumin. Both Kupffer cells and liver endothelial cells took up and degraded the immune complexes, but there was a clear delay in the degradation of immune complexes as compared to degradation of ligands taken up via scavenger receptors. The kinetics of the endocytosis of scavenger receptor ligand was unaffected by simultaneous uptake of immune complexes. Experiments using both biochemical and morphological techniques indicated that the delayed degradation was due to a late arrival of the immune complexes at the lysosomes, which partly was explained by retroendocytosis of immune complexes. Electron microscopy studies revealed that the immune complexes were retained in the early endosomes that remained accessible to other endocytic markers such as ovalbumin. In addition, the immune complexes were seen in multivesicular compartments apparently devoid of other endocytic markers. Finally, the immune complexes were degraded in the same lysosomes as the ligands of scavenger receptors. Thus, immune complexes seem to follow an endocytic pathway that is kinetically or maybe morphologically different from that followed by scavenger and mannose receptor ligands.

scholarly journals New Scavenger Receptor-Like Receptors for the Binding of Lipopolysaccharide to Liver Endothelial and Kupffer Cells

1998 ◽  
Vol 66 (11) ◽  
pp. 5107-5112 ◽  
Author(s):  
Marijke van Oosten ◽  
Erika van de Bilt ◽  
Theo J. C. van Berkel ◽  
Johan Kuiper
Keyword(s):  
Endothelial Cells ◽  
Kupffer Cells ◽  
Binding Sites ◽  
Oxidized Ldl ◽  
Scavenger Receptor ◽  
Scavenger Receptors ◽  
Liver Endothelial Cells ◽  
Parenchymal Cells

ABSTRACT Lipopolysaccharide (LPS) is cleared from the blood mainly by the liver. The Kupffer cells are primarily responsible for this clearance; liver endothelial and parenchymal cells contribute to a lesser extent. Although several binding sites have been described, only CD14 is known to be involved in LPS signalling. Among the other LPS binding sites that have been identified are scavenger receptors. Scavenger receptor class A (SR-A) types I and II are expressed in the liver on endothelial cells and Kupffer cells, and a 95-kDa receptor, identified as macrosialin, is expressed on Kupffer cells. In this study, we examined the role of scavenger receptors in the binding of LPS by the liver in vivo and in vitro. Fucoidin, a scavenger receptor ligand, significantly reduced the clearance of 125I-LPS from the serum and decreased the liver uptake of 125I-LPS about 40%. Within the liver, the in vivo binding of 125I-LPS to Kupffer and liver endothelial cells was decreased 72 and 71%, respectively, while the binding of 125I-LPS to liver parenchymal cells increased 34% upon fucoidin preinjection. Poly(I) inhibited the binding of 125I-LPS to Kupffer and endothelial cells in vitro 73 and 78%, respectively, while poly(A) had no effect. LPS inhibited the binding of acetylated low-density lipoprotein (acLDL) to Kupffer and liver endothelial cells 40 and 55%, respectively, and the binding of oxidized LDL (oxLDL) to Kupffer and liver endothelial cells 65 and 61%, respectively. oxLDL and acLDL did not significantly inhibit the binding of LPS to these cells. We conclude that on both endothelial cells and Kupffer cells, LPS binds mainly to scavenger receptors, but SR-A and macrosialin contribute to a limited extent to the binding of LPS.

Wortmannin-sensitive trafficking steps in the endocytic pathway in rat liver endothelial cells

2001 ◽  
Vol 357 (2) ◽  
pp. 497-503 ◽  
Author(s):  
Rune KJEKEN ◽  
Seyed A. MOUSAVI ◽  
Andreas BRECH ◽  
Gareth GRIFFITHS ◽  
Trond BERG
Keyword(s):  
Endothelial Cells ◽  
Rat Liver ◽  
Intracellular Transport ◽  
Mannose Receptor ◽  
Endocytic Pathway ◽  
Receptor Ligand ◽  
Surface Receptors ◽  
Phosphatidylinositol Kinases ◽  
Early Endosomes ◽  
Liver Endothelial Cells

Liver endothelial cells (LECs) play an important homoeostatic role by removing potentially harmful macromolecules from blood. The extremely efficient endocytosis in LECs makes these cells an interesting model for the study of the involvement of phosphoinositides in the different steps of the endocytic process. In the present investigation we have studied the effect of wortmannin, an inhibitor of phosphatidylinositol kinases, on uptake, recycling and intracellular transport of 125I-labelled ovalbumin, which is taken up in LECs via mannose-receptor-mediated endocytosis. Wortmannin was found to inhibit both uptake and degradation of ovalbumin. Further studies indicated that the reduced uptake via the mannose receptor was due both to a reduction of the number of surface receptors and a reduction in the rate of receptor–ligand internalization. Transport of ligand from endosomes to lysosomes was prevented, leading to increased recycling of internalized ligand. Wortmannin treatment released the Rab5 effector EEA1 from the endosomes and caused reduced size of early endosomes.

Both Kupffer cells and liver endothelial cells play an important role in the clearance of IgA and IgG immune complexes

1992 ◽  
Vol 143 (2) ◽  
pp. 219-224 ◽  
Author(s):  
W.M.J.M. Bogers ◽  
R.-K. Stad ◽  
L.A. Van Es ◽  
M.R. Daha
Keyword(s):  
Endothelial Cells ◽  
Kupffer Cells ◽  
Immune Complexes ◽  
Liver Endothelial Cells

Scavenger-receptor-mediated endocytosis in endocardial endothelial cells of Atlantic cod Gadus morhua.

1998 ◽  
Vol 201 (11) ◽  
pp. 1707-1718 ◽  
Author(s):  
K K Sørensen ◽  
J Melkko ◽  
B Smedsrød
Keyword(s):  
Endothelial Cells ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Scavenger Receptor ◽  
Scavenger Receptors ◽  
Type I ◽  
Receptor Ligands ◽  
Endocardial Endothelial Cells ◽  
Scavenger Receptor Ligands

Scavenger receptors are multifunctional integral membrane proteins that mediate the endocytosis of many different macromolecular polyanions and also participate in host defence reactions and cell adherance. In Atlantic cod (Gadus morhua L.), two intravenously injected scavenger receptor ligands, [125I]tyramine-cellobiose-labelled formaldehyde-treated serum albumin (125I-TC-FSA) and 125I-labelled N-terminal propeptide of type I procollagen (125I-PINP), distributed mainly to the heart. Cellular uptake was visualized by injections of fluorescently labelled FSA (FITC-FSA), which was recovered in discrete vesicles in endocardial endothelial cells of both heart chambers. Studies in vitro showed that radioiodinated FSA and PINP were endocytosed and degraded very efficiently by cultured atrial endocardial endothelial cells. Moreover, uptake of 125I-FSA was Ca2+-independent. Out of a range of unlabelled ligands, only the scavenger receptor ligands FITC-FSA, polyinosinic acid and, to a varying extent, FSA, acetylated low-density lipoprotein (AcLDL) and PINP, were able to compete with radioiodinated FSA, PINP or AcLDL for uptake in isolated endocardial cells. From our findings, we conclude that the endocardial endothelial cells are major carriers of scavenger receptors in cod. In addition, our results strengthen the hypothesis that these cells in cod play the same important function as that established for the scavenger endothelial cells of the mammalian liver.

Liver Kupffer cells rapidly remove red blood cell–derived vesicles from the circulation by scavenger receptors

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 2141-2145 ◽  
Author(s):  
Frans L. A. Willekens ◽  
Jan M. Werre ◽  
J. Kar Kruijt ◽  
Bregt Roerdinkholder-Stoelwinder ◽  
Yvonne A. M. Groenen-Döpp ◽  
...  
Keyword(s):  
Blood Cell ◽  
Kupffer Cells ◽  
Blood Cells ◽  
Scavenger Receptor ◽  
Scavenger Receptors ◽  
Receptor Ligands ◽  
Liver Uptake ◽  
Polyinosinic Acid ◽  
Important Pathway ◽  
Human Rbcs

Abstract Previous studies have shown that during the lifespan of red blood cells (RBCs) 20% of hemoglobin is lost by shedding of hemoglobin-containing vesicles. However, the fate of these vesicles is unknown. To study this fate we used a rat model, after having established that rat RBCs lose hemoglobin in the same way as human RBCs, and that RBC-derived vesicles are preferentially labeled by \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{Na}_{2}^{51}\) \end{document} CrO4. Such labeled vesicles were injected into recipient rats. Within 5 minutes, 80% of the radioactivity was cleared from the circulation with a concomitant uptake by the liver of 55% of the injected dose. After 30 minutes, Kupffer cells contained considerable amounts of hemoglobin and were shown to be responsible for 92% of the liver uptake. Vesicle clearance from the blood as well as liver uptake were significantly inhibited by preinjection of the scavenger-receptor ligands polyinosinic acid and phosphatidylserine. We conclude that in rats Kupffer cells rapidly remove RBC-derived vesicles from the circulation, mainly by scavenger receptors. The same mechanism is likely to be responsible for the elimination of human RBC vesicles, thereby constituting an important pathway for the breakdown of RBCs in humans.

scholarly journals Characterization of the interaction both in vitro and in vivo of tissue-type plasminogen activator (t-PA) with rat liver cells. Effects of monoclonal antibodies to t-PA

1992 ◽  
Vol 284 (2) ◽  
pp. 545-550 ◽  
Author(s):  
M Otter ◽  
J Kuiper ◽  
R Bos ◽  
D C Rijken ◽  
T J van Berkel
Keyword(s):  
Endothelial Cells ◽  
Mannose Receptor ◽  
Liver Cells ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Liver Endothelial Cells ◽  
Parenchymal Cells

The interaction of 125I-labelled tissue-type plasminogen activator (125I-t-PA) with freshly isolated rat parenchymal and endothelial liver cells was studied. Binding experiments at 4 degrees C with parenchymal cells and endothelial liver cells indicated the presence of 68,000 and 44,000 high-affinity t-PA-binding sites, with an apparent Kd of 3.5 and 4 nM respectively. Association of 125I-t-PA with parenchymal cells was Ca(2+)-dependent and was not influenced by asialofetuin, a known ligand for the galactose receptor. Association of 125I-t-PA with liver endothelial cells was Ca(2+)-dependent and mannose-specific, since ovalbumin (a mannose-terminated glycoprotein) inhibited the cell association of t-PA. Association of 125I-t-PA with liver endothelial cells was inhibited by anti-(human mannose receptor) antiserum. Anti-(galactose receptor) IgG had no effect on 125I-t-PA association with either cell type. Degradation of 125I-t-PA at 37 degrees C by both cell types was inhibited by chloroquine or NH4Cl, indicating that t-PA is degraded lysosomally. in vitro experiments with three monoclonal antibodies (MAbs) demonstrated that anti-t-PA MAb 1-3-1 specifically decreased association of 125I-t-PA with the endothelial cells, and anti-t-PA Mab 7-8-4 inhibited association with the parenchymal cells. Results of competition experiments in rats in vivo with these antibodies were in agreement with findings in vitro. Both antibodies decreased the liver uptake of 125I-t-PA, while a combination of the two antibodies was even more effective in reducing the liver association of 125I-t-PA and increasing its plasma half-life. We conclude from these data that clearance of t-PA by the liver is regulated by at least two pathways, one on parenchymal cells (not galactose/mannose-mediated) and another on liver endothelial cells (mediated by a mannose receptor). Results with the MAbs imply that two distinct sites on the t-PA molecule are involved in binding to parenchymal cells and liver endothelial cells.

scholarly journals Endocytosis of formaldehyde-treated serum albumin via scavenger pathway in liver endothelial cells

1984 ◽  
Vol 218 (1) ◽  
pp. 81-86 ◽  
Author(s):  
R Blomhoff ◽  
W Eskild ◽  
T Berg
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Surface Culture ◽  
Rat Liver Cells ◽  
Liver Endothelial Cells ◽  
Isolated Liver

Denatured or modified proteins (including albumin and low-density lipoprotein) are catabolized in vitro via scavenger receptors. We have studied the distribution of formaldehyde-denatured albumin in rat liver cells after intravenous injection of tracer doses of the protein. At 12 min after injection, most of the formaldehyde-denatured albumin (about 70% of the injected dose) was recovered in liver endothelial cells. Furthermore, isolated liver endothelial cells in suspension and in surface culture took up formaldehyde-denatured albumin by receptor-mediated endocytosis. Our data indicate that the scavenger receptor in liver is mainly located on the endothelial cells. Implications for the catabolism of low-density lipoproteins are discussed.

scholarly journals Clearance of NH2-terminal propeptides of types I and III procollagen is a physiological function of the scavenger receptor in liver endothelial cells.

1994 ◽  
Vol 179 (2) ◽  
pp. 405-412 ◽  
Author(s):  
J Melkko ◽  
T Hellevik ◽  
L Risteli ◽  
J Risteli ◽  
B Smedsrød
Keyword(s):  
Endothelial Cells ◽  
Physiological Function ◽  
Scavenger Receptor ◽  
Alpha Phase ◽  
Maximum Diameter ◽  
Type I ◽  
Waste Products ◽  
Type I Procollagen ◽  
Polyinosinic Acid ◽  
Liver Endothelial Cells

This study was undertaken to determine the fate of circulating NH2-terminal propeptide of type I procollagen (PINP) in rats. Radiolabeled PINP showed a biphasic serum decay curve after intravenous injection. 79% of the material disappeared from the blood during the initial alpha-phase (t1/2 alpha = 0.6 min), while the remaining 21% was eliminated with a t1/2 beta of 3.3 min. The major site of uptake was the liver, 78, 1, and 21% of its radioactivity being recovered in isolated liver endothelial cells (LEC), Kupffer cells, and parenchymal cells, respectively. In LEC, fluorescently labeled PINP accumulated in small (0.1 microns) peripheral and larger (> 0.1 microns) perinuclear vesicles within 10 min at 37 degrees C after a binding pulse at 4 degrees C. These grew in size with increasing chasing time, reaching a maximum diameter of 1 microns or more after 30 min, and taking the shape of rings that were stained only along their periphery. At chase intervals exceeding 30 min, the size of the vesicles decreased, and after 60 min the stain appeared in smaller, densely stained perinuclearly located vesicles. Degradation of 125I-PINP to free smaller fragments and 125I- was significant after 30 min. Only formaldehyde-treated albumin, acetylated LDL, polyinosinic acid and NH2-terminal propeptide of type III procollagen (PIIINP) competed with PINP for uptake. These findings indicate that clearance of PINP and PIIINP, which are normal waste products generated in large quantities, is a physiological function of the scavenger receptor in LEC.

CD36 Is Not Involved in Scavenger Receptor–Mediated Endocytic Uptake of Glycolaldehyde- and Methylglyoxal-Modified Proteins by Liver Endothelial Cells

2005 ◽  
Vol 137 (5) ◽  
pp. 607-616 ◽  
Author(s):  
Keisuke Nakajou ◽  
Seikoh Horiuchi ◽  
Masakazu Sakai ◽  
Kenshiro Hirata ◽  
Makiko Tanaka ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Scavenger Receptor ◽  
Liver Endothelial Cells ◽  
Modified Proteins

Morphological Characterization of Scavenger Receptor-Mediated Processing of Modified Lipoproteins by Rat Liver Endothelial Cells

1994 ◽  
Vol 210 (1) ◽  
pp. 62-70 ◽  
Author(s):  
Sebastiaan Esbach ◽  
Monique F. Stins ◽  
Adriaan Brouwer ◽  
Paul J.M. Roholl ◽  
Theo J.C. van Berkel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Rat Liver ◽  
Scavenger Receptor ◽  
Morphological Characterization ◽  
Modified Lipoproteins ◽  
Liver Endothelial Cells
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