scholarly journals CD36 Mediates the Innate Host Response to β-Amyloid

2003 ◽  
Vol 197 (12) ◽  
pp. 1657-1666 ◽  
Author(s):  
Joseph B. El Khoury ◽  
Kathryn J. Moore ◽  
Terry K. Means ◽  
Josephine Leung ◽  
Kinya Terada ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Senile Plaques ◽  
Scavenger Receptor ◽  
Intracerebral Injection ◽  
Innate Response ◽  
Macrophage Response ◽  
Class B ◽  
Β Amyloid ◽  
Recognition Receptor

Accumulation of inflammatory microglia in Alzheimer's senile plaques is a hallmark of the innate response to β-amyloid fibrils and can initiate and propagate neurodegeneration characteristic of Alzheimer's disease (AD). The molecular mechanism whereby fibrillar β-amyloid activates the inflammatory response has not been elucidated. CD36, a class B scavenger receptor, is expressed on microglia in normal and AD brains and binds to β-amyloid fibrils in vitro. We report here that microglia and macrophages, isolated from CD36 null mice, had marked reductions in fibrillar β-amyloid–induced secretion of cytokines, chemokines, and reactive oxygen species. Intraperitoneal and stereotaxic intracerebral injection of fibrillar β-amyloid in CD36 null mice induced significantly less macrophage and microglial recruitment into the peritoneum and brain, respectively, than in wild-type mice. Our data reveal that CD36, a major pattern recognition receptor, mediates microglial and macrophage response to β-amyloid, and imply that CD36 plays a key role in the proinflammatory events associated with AD.

scholarly journals Mechanism of Cellular Formation and In Vivo Seeding Effects of Hexameric β-Amyloid Assemblies

2021 ◽  
Author(s):  
Céline Vrancx ◽  
Devkee M. Vadukul ◽  
Nuria Suelves ◽  
Sabrina Contino ◽  
Ludovic D’Auria ◽  
...  
Keyword(s):  
Cell Lines ◽  
Self Assembly ◽  
Amyloid Fibrils ◽  
Senile Plaques ◽  
Amyloid Peptide ◽  
Cellular Models ◽  
Aβ Aggregation ◽  
Β Amyloid

AbstractThe β-amyloid peptide (Aβ) is found as amyloid fibrils in senile plaques, a typical hallmark of Alzheimer’s disease (AD). However, intermediate soluble oligomers of Aβ are now recognized as initiators of the pathogenic cascade leading to AD. Studies using recombinant Aβ have shown that hexameric Aβ in particular acts as a critical nucleus for Aβ self-assembly. We recently isolated hexameric Aβ assemblies from a cellular model, and demonstrated their ability to enhance Aβ aggregation in vitro. Here, we report the presence of similar hexameric-like Aβ assemblies across several cellular models, including neuronal-like cell lines. In order to better understand how they are produced in a cellular context, we investigated the role of presenilin-1 (PS1) and presenilin-2 (PS2) in their formation. PS1 and PS2 are the catalytic subunits of the γ-secretase complex that generates Aβ. Using CRISPR-Cas9 to knockdown each of the two presenilins in neuronal-like cell lines, we observed a direct link between the PS2-dependent processing pathway and the release of hexameric-like Aβ assemblies in extracellular vesicles. Further, we assessed the contribution of hexameric Aβ to the development of amyloid pathology. We report the early presence of hexameric-like Aβ assemblies in both transgenic mice brains exhibiting human Aβ pathology and in the cerebrospinal fluid of AD patients, suggesting hexameric Aβ as a potential early AD biomarker. Finally, cell-derived hexameric Aβ was found to seed other human Aβ forms, resulting in the aggravation of amyloid deposition in vivo and neuronal toxicity in vitro.

Linoleic acid treatment increases the expression of scavenger receptor class B type 1 (SR-B1) in in-vitro model

2021 ◽  
Vol 331 ◽  
pp. e128
Author(s):  
N.-A. Azemi ◽  
L. Abu-Bakar ◽  
N. Ismail ◽  
V. Sevakumaran ◽  
T.-S. Tengku-Muhammad
Keyword(s):  
Linoleic Acid ◽  
Acid Treatment ◽  
In Vitro Model ◽  
Scavenger Receptor ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Vitro Model

Abstract 11607: Novel Assay for Detection of LDL Transcytosis Across Coronary Endothelium Reveals an Unexpected Role for SR-B1

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Susan M Armstrong ◽  
Michael G Sugiyama ◽  
Andrew Levy ◽  
Dante Neculai ◽  
Mark Roufaiel ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Fluorescence Microscopy ◽  
Ex Vivo ◽  
Scavenger Receptor ◽  
Intercellular Junctions ◽  
Live Cells ◽  
Human Coronary Artery ◽  
Class B ◽  
Major Route

Introduction: Retention of LDL beneath the arterial endothelium initiates an inflammatory response culminating in atherosclerosis. How LDL crosses the endothelium to enter the arterial wall remains unknown. While LDL could conceivably pass between endothelial cells (paracellularly) or through them (transcytosis), electron microscopy studies in animals revealed LDL in intracellular vesicles and none at intercellular junctions. This, combined with the absence of endothelial injury or intercellular gaps in early atherosclerosis, suggests that transcytosis is the major route. However, technical challenges with studying transcytosis have made confirming and extending these findings difficult. We developed and validated a novel assay for measuring the transcytosis of native LDL across live human coronary artery endothelium in vitro. Using this assay, we propose to elucidate the regulation of LDL transcytosis and have identified a novel role for SR-B1. Methods and Results: Experiments were performed using primary human coronary artery endothelial monolayers. Transcytosis was quantified in single live cells in real time using total internal reflectance fluorescence microscopy. Transcytosis of LDL was saturable and inhibited by excess unlabeled LDL. By fluorescence microscopy we found that DiI-LDL colocalized significantly with scavenger receptor, class B, type 1 (SR-B1). Unexpectedly, overexpression of SR-BI resulted in increased LDL transcytosis, while knockdown of SR-BI by siRNA inhibited transcytosis. Excess HDL, the canonical SR-B1 ligand, also decreased LDL transcytosis. To confirm the occurrence of transcytosis in an intact vessel, we perfused murine aortas ex vivo with both LDL and dextran of a smaller molecular radius. We observed the accumulation of subendothelial LDL without dextran, indicating that transcytosis of LDL occurs in intact vessels. Conclusions: The accumulation of LDL in the subendothelial intima is the first step of atherosclerosis yet little is known about how it occurs. Our data suggests that transcytosis of LDL is an important contributor, particularly in the early stages of the disease. By identifying the mechanisms of transcytosis, our work could have important implications for its pathogenesis and therapy.

Inhibitory activity of stilbenes on Alzheimer’s β-amyloid fibrils in vitro

2007 ◽  
Vol 15 (2) ◽  
pp. 1160-1167 ◽  
Author(s):  
Céline Rivière ◽  
Tristan Richard ◽  
Lysiane Quentin ◽  
Stéphanie Krisa ◽  
Jean-Michel Mérillon ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Amyloid Fibrils ◽  
Β Amyloid

Nicotine breaks down preformed Alzheimer’s β-amyloid fibrils in vitro

2002 ◽  
Vol 52 (9) ◽  
pp. 880-886 ◽  
Author(s):  
Kenjiro Ono ◽  
Kazuhiro Hasegawa ◽  
Masahito Yamada ◽  
Hironobu Naiki
Keyword(s):  
Amyloid Fibrils ◽  
Β Amyloid

scholarly journals A Human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo

Hepatology ◽  
2011 ◽  
Vol 55 (2) ◽  
pp. 364-372 ◽  
Author(s):  
Philip Meuleman ◽  
Maria Teresa Catanese ◽  
Lieven Verhoye ◽  
Isabelle Desombere ◽  
Ali Farhoudi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Scavenger Receptor ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Viral Spread ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Scavenger Receptor Class B Type I Is More Conducive to Hepatitis C Virus Invasion Compared with Low-Density Lipoprotein Receptor

2020 ◽  
Author(s):  
Xiangyi Cao ◽  
Qiong Kang ◽  
Deng Jiang ◽  
Jun Xiao ◽  
Yanyu Zhang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Type I ◽  
Lipoprotein Receptor ◽  
Scavenger Receptor Class ◽  
Recombinant Cells ◽  
Class B ◽  
Density Lipoprotein Receptor

Abstract Background: Hepatitis C virus is the major cause of chronic hepatitis which may deteriorate into liver cirrhosis or hepatocellular carcinoma. A number of studies have demonstrated that HCV cell entry is a complex multi-step process involving several cellular proteins, such as scavenger receptor class B type I (SR-BI), tetraspanin CD81, tight junction protein claudin-1 (CLDN-1) and occludin (OCLN). The low-density lipoprotein receptor (LDLR) is an important factor during the initial HCV particle-binding step, which interacts with the complex formed between the virus particle and the lipoprotein in the blood. However, the process of HCV early infection is not well-established, with many details remaining to be elucidated.This research aimed to study the early entry stage of HCV virus particles and the role of LDLR more effectively.Methods: Recombinant murine cell models of HCV infection in vitro was constructed, that expressed human HCV receptors, such as LDLR, CD81, SR BI, CLDN-1, and OCLN. These factors were also introduced to mice by hydrodynamic delivery to construct a humanized mouse model of HCV infection in vivo.Expression levels of the mRNA of HCV entry factors in recombinant cells were measured by qRT-PCR.Western blotting was used to determine whether the recombinant cells successfully expressed cellular proteins. HCV RNA was assayed by q-PCR following the incublation of HCVsd and HCVcc with the transgenice.Results: Transgenic murine cell lines and mice were developed successfully, and expressed four or five human HCV entry factors in tandem or individually, respectively. We found that all of these transgenic cells and mice were susceptible to HCV, and five entry factors (5EF) rendered higher infectivity. Additionally, we observed that four entry factors (4EF/hLDLR-) could facilitate abundant HCV entry, but four other factors (4EF/hSR-BI-) were less effective.Conclusions: Whether in vitro or in vivo, SR-BI is an essential factor in HCV invasion, and target cells and mice were more vulnerable to the virus in the presence of SR-BI than LDLR. These results suggested that SR-BI may be a potential drug target to inhibit HCV early infection, and the absence of LDLR could reduce the infectivity to the virus.

Estrogen has anti-amyloidogenic effects on Alzheimer’s β-amyloid fibrils in vitro

2007 ◽  
Vol 359 (3) ◽  
pp. 697-702 ◽  
Author(s):  
Akiyoshi Morinaga ◽  
Mie Hirohata ◽  
Kenjiro Ono ◽  
Masahito Yamada
Keyword(s):  
Amyloid Fibrils ◽  
Β Amyloid
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