Scavenger Receptors: Novel Roles in the Pathogenesis of Liver Inflammation and Cancer

Patten, Daniel; Wilkinson, Alex L; O'Keeffe, Ayla; Shetty, Shishir

doi:10.1055/s-0041-1733876

Cited by 18 publications

(10 citation statements)

References 214 publications

(300 reference statements)

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“…Liver sinusoidal endothelial cells also express an unusual complement of scavenger receptors which recognize, bind, and rapidly internalize an enormous diversity of extracellular ligands (Shetty et al, 2018). These are characterized into classes A to J depending on their ligand recognition and structural properties (Patten et al, 2021) and LSEC express receptors in classes SR-B, E, F, G, and H to support clearance of fatty acids, lipids ECM proteins, glycosaminoglycan molecules and apoptotic cells. This significant endocytic capability supports the immune regulation (Knolle and Limmer, 2001), metabolic capacity (Li et al, 2011) and "waste management" (Smedsrod, 2004) functions of the liver.…”

Section: Liver Sinusoidal Endothelial Cell Structure and Functionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Liver Sinusoidal Endothelial Cell Structure and Functionmentioning

confidence: 99%

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

et al. 2022

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“…Based on structural and functional properties, SRs are divided into classes A to J, which have little or no structural resemblance. 3 However, the members within each class have a primary sequence similarity. SRs are usually defined as cell‐surface receptors and are typically expressed on macrophages, regulating macrophage endocytosis and immune functions.…”

mentioning

confidence: 99%

Scavenger Receptors in Myocardial Infarction and Ischemia/Reperfusion Injury: The Potential for Disease Evaluation and Therapy

Zhang

Wen

Liu

et al. 2023

JAHA

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Scavenger receptors (SRs) are a structurally heterogeneous superfamily of evolutionarily conserved receptors that are divided into classes A to J. SRs can recognize multiple ligands, such as modified lipoproteins, damage‐associated molecular patterns, and pathogen‐associated molecular patterns, and regulate lipid metabolism, immunity, and homeostasis. According to the literature, SRs may play a critical role in myocardial infarction and ischemia/reperfusion injury, and the soluble types of SRs may be a series of promising biomarkers for the diagnosis and prognosis of patients with acute coronary syndrome or acute myocardial infarction. In this review, we briefly summarize the structure and function of SRs and discuss the association between each SR and ischemic cardiac injury in patients and animal models in detail. A better understanding of the effect of SRs on ischemic cardiac injury will inspire novel ideas for therapeutic drug discovery and disease evaluation in patients with myocardial infarction.

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“…This altered signal could be indicative of an increased molecule trafficking during the neuroinflammation progression [ 50 , 51 , 52 ]. Moreover, different SRs are expressed both by endothelial cells and by a plethora of leukocytes such as lymphocytes and neutrophils [ 53 , 54 ]. Therefore, these immune responsive cells coming from systemic circulation can undesirably sustain and exacerbate inflammation already taking place in AD-affected brains by the recruitment of resident glial and macrophage cells.…”

Section: Discussionmentioning

confidence: 99%

Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer’s Disease Progression

Baldini

Greco

Lomi

et al. 2022

IJMS

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Alzheimer’s disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets.

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Scavenger Receptors: Novel Roles in the Pathogenesis of Liver Inflammation and Cancer

Cited by 18 publications

References 214 publications

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

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

Scavenger Receptors in Myocardial Infarction and Ischemia/Reperfusion Injury: The Potential for Disease Evaluation and Therapy

Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer’s Disease Progression

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