Density of Conjugated Antibody Determines the Extent of Fc Receptor Dependent Capture of Nanoparticles by Liver Sinusoidal Endothelial Cells

ACS Nano ◽  
2021 ◽  
Author(s):  
Cinja Kappel ◽  
Christine Seidl ◽  
Carolina Medina-Montano ◽  
Meike Schinnerer ◽  
Irina Alberg ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fc Receptor ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells

scholarly journals The Contribution of Liver Sinusoidal Endothelial Cells to Clearance of Therapeutic Antibody

2022 ◽  
Vol 12 ◽  
Author(s):  
Bethany H. James ◽  
Pantelitsa Papakyriacou ◽  
Matthew J. Gardener ◽  
Louise Gliddon ◽  
Christopher J. Weston ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Liver Disease ◽  
Immune Cells ◽  
High Specificity ◽  
Fc Receptor ◽  
Membrane Receptors ◽  
Pharmacokinetic Studies ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells

Many chronic inflammatory diseases are treated by administration of “biological” therapies in terms of fully human and humanized monoclonal antibodies or Fc fusion proteins. These tools have widespread efficacy and are favored because they generally exhibit high specificity for target with a low toxicity. However, the design of clinically applicable humanized antibodies is complicated by the need to circumvent normal antibody clearance mechanisms to maintain therapeutic dosing, whilst avoiding development of off target antibody dependent cellular toxicity. Classically, professional phagocytic immune cells are responsible for scavenging and clearance of antibody via interactions with the Fc portion. Immune cells such as macrophages, monocytes, and neutrophils express Fc receptor subsets, such as the FcγR that can then clear immune complexes. Another, the neonatal Fc receptor (FcRn) is key to clearance of IgG in vivo and serum half-life of antibody is explicitly linked to function of this receptor. The liver is a site of significant expression of FcRn and indeed several hepatic cell populations including Kupffer cells and liver sinusoidal endothelial cells (LSEC), play key roles in antibody clearance. This combined with the fact that the liver is a highly perfused organ with a relatively permissive microcirculation means that hepatic binding of antibody has a significant effect on pharmacokinetics of clearance. Liver disease can alter systemic distribution or pharmacokinetics of antibody-based therapies and impact on clinical effectiveness, however, few studies document the changes in key membrane receptors involved in antibody clearance across the spectrum of liver disease. Similarly, the individual contribution of LSEC scavenger receptors to antibody clearance in a healthy or chronically diseased organ is not well characterized. This is an important omission since pharmacokinetic studies of antibody distribution are often based on studies in healthy individuals and thus may not reflect the picture in an aging or chronically diseased population. Therefore, in this review we consider the expression and function of key antibody-binding receptors on LSEC, and the features of therapeutic antibodies which may accentuate clearance by the liver. We then discuss the implications of this for the design and utility of monoclonal antibody-based therapies.

CD8+ T cell tolerance induced by liver sinusoidal endothelial cells depends on ICOS/ICOSL interactions

2004 ◽  
Vol 42 (01) ◽  
Author(s):  
L Diehl ◽  
G Wingender ◽  
A Hutloff ◽  
R Kroczek ◽  
S Porcelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells

scholarly journals Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance

2005 ◽  
Vol 35 (10) ◽  
pp. 2970-2981 ◽  
Author(s):  
Andreas Limmer ◽  
Jutta Ohl ◽  
Gerhard Wingender ◽  
Martina Berg ◽  
Frank Jüngerkes ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Cross Presentation

Quantification of fenestrations in liver sinusoidal endothelial cells by atomic force microscopy

Micron ◽  
2017 ◽  
Vol 101 ◽  
pp. 48-53 ◽  
Author(s):  
Bartlomiej Zapotoczny ◽  
Karolina Szafranska ◽  
Edyta Kus ◽  
Stefan Chlopicki ◽  
Marek Szymonski
Keyword(s):  
Atomic Force Microscopy ◽  
Endothelial Cells ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Force Microscopy ◽  
Atomic Force
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