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Cells
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Scavenger Receptor Structure and Function in Health and Disease
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Scavenger Receptor Structure and Function in Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 31379

Special Issue Editors

Dr. Lozano Francisco

E-Mail Website
Guest Editor
Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, Servei d’Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
Prof. Kenneth Linton

E-Mail Website
Guest Editor
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Interests: scavenger receptors; lipid transport; ABC transporters; ABCB4; drug efflux pumps; ABCB1

Special Issue Information

Dear Colleagues,

Scavenger receptors (SR) are defined as a large and structurally diverse group of innate immune receptors with a broad binding specificity, allowing them to participate in a wide range of basic homeostatic functions. They typically bind to multiple ligands (namely, those of a polyanionic nature) and promote the recognition and removal of non-self (e.g., microbial) and/or altered-self (e.g., oxidized or acetylated lipoproteins) noxious structures. They present as membrane-bound and/or soluble receptors expressed by cells of hematopoietic (myeloid, lymphoid) and/or non-hematopoeitic (e.g., eptithelial, endothelial) origin.

Since first description and cloning of its prototypical member—the macrophage SR class A type I (SR-AI)—the SR family has been in constant and progressive expansion, and its study has attracted growing interest, which parallels that in innate immunity. As a result, the involvement of different SR members in quite different functions (e.g, lipid metabolism and atherosclerosis, pathogen recognition, the modulation of the immune response, epithelial homeostasis, stem cell biology, and tumor development) has been reported. This information has brought to us the possibility of therapeutically targeting SR for a number of physiologic and pathologic states, which will pave the way for the more comprehensive use of SR in the clinic.

This Special Issue seeks reviews and original papers covering but not limited to basic knowledge and potential applications of SR to diagnose and cure human disorders.

Dr. Lozano Francisco
Prof. Kenneth Linton
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (4 papers)

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Review

17 pages, 891 KiB  
Review
Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents
by María Velasco-de Andrés, Sergi Casadó-Llombart, Cristina Català, Alejandra Leyton-Pereira, Francisco Lozano and Fernando Aranda
Cells 2020, 9(12), 2589; https://doi.org/10.3390/cells9122589 - 3 Dec 2020
Cited by 19 | Viewed by 4882
Abstract
CD5 and CD6 are closely related signal-transducing class I scavenger receptors mainly expressed on lymphocytes. Both receptors are involved in the modulation of the activation and differentiation cell processes triggered by clonotypic antigen-specific receptors present on T and B cells (TCR and BCR, [...] Read more.
CD5 and CD6 are closely related signal-transducing class I scavenger receptors mainly expressed on lymphocytes. Both receptors are involved in the modulation of the activation and differentiation cell processes triggered by clonotypic antigen-specific receptors present on T and B cells (TCR and BCR, respectively). To serve such a relevant immunomodulatory function, the extracellular region of CD5 and CD6 interacts with soluble and/or cell-bound endogenous counterreceptors but also microbial-associated molecular patterns (MAMPs). Evidence from genetically-modified mouse models indicates that the absence or blockade of CD5- and CD6-mediated signals results in dysregulated immune responses, which may be deleterious or advantageous in some pathological conditions, such as infection, cancer or autoimmunity. Bench to bedside translation from transgenic data is constrained by ethical concerns which can be overcome by exogenous administration of soluble proteins acting as decoy receptors and leading to transient “functional knockdown”. This review gathers information currently available on the therapeutic efficacy of soluble CD5 and CD6 receptor infusion in different experimental models of disease. The existing proof-of-concept warrants the interest of soluble CD5 and CD6 as safe and efficient immunotherapeutic agents in diverse and relevant pathological conditions. Full article
(This article belongs to the Special Issue Scavenger Receptor Structure and Function in Health and Disease)
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34 pages, 3487 KiB  
Review
Systemic Glycosaminoglycan Clearance by HARE/Stabilin-2 Activates Intracellular Signaling
by Paul H. Weigel
Cells 2020, 9(11), 2366; https://doi.org/10.3390/cells9112366 - 28 Oct 2020
Cited by 15 | Viewed by 4011
Abstract
Scavenger receptors perform essential functions, critical to maintaining mammalian physiologic homeostasis by continuously clearing vast numbers of biomolecules from blood, interstitial fluid and lymph. Stabilin-2 (Stab2) and the Hyaluronic Acid Receptor for Endocytosis (HARE), a proteolytic isoform of Stab2, are important scavenger receptors [...] Read more.
Scavenger receptors perform essential functions, critical to maintaining mammalian physiologic homeostasis by continuously clearing vast numbers of biomolecules from blood, interstitial fluid and lymph. Stabilin-2 (Stab2) and the Hyaluronic Acid Receptor for Endocytosis (HARE), a proteolytic isoform of Stab2, are important scavenger receptors responsible for the specific binding and internalization (leading to degradation) of 22 discrete molecules, macromolecular complexes and cell types. One-third of these ligands are glycosaminoglycans (GAGs). Full-length Stab2, but not HARE, mediates efficient phagocytosis of apoptotic cells and bacteria via binding to target surface ligands. HARE, the C-terminal half of Stab2, mediates endocytosis of all the known soluble ligands. HA was the first ligand identified, in 1981, prior to receptor purification or cloning. Seven other GAG ligands were subsequently identified: heparin, dermatan sulfate, chondroitin and chondroitin sulfates A, C, D and E. Synthetic dextran sulfate is also a GAG mimic and ligand. HARE signaling during HA endocytosis was first discovered in 2008, and we now know that activation of HARE/Stab2 signaling is stimulated by receptor-mediated endocytosis or phagocytosis of many, but not all, of its ligands. This review focuses on the HARE-mediated GAG activation of intracellular signaling, particularly the Extracellular Signal-Regulated Kinase 1/2 pathway. Full article
(This article belongs to the Special Issue Scavenger Receptor Structure and Function in Health and Disease)
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Graphical abstract

41 pages, 2689 KiB  
Review
The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring
by Kamila Puchałowicz and Monika Ewa Rać
Cells 2020, 9(8), 1877; https://doi.org/10.3390/cells9081877 - 11 Aug 2020
Cited by 45 | Viewed by 7444
Abstract
CD36 is a multiligand receptor contributing to glucose and lipid metabolism, immune response, inflammation, thrombosis, and fibrosis. A wide range of tissue expression includes cells sensitive to metabolic abnormalities associated with metabolic syndrome and diabetes mellitus (DM), such as monocytes and macrophages, epithelial [...] Read more.
CD36 is a multiligand receptor contributing to glucose and lipid metabolism, immune response, inflammation, thrombosis, and fibrosis. A wide range of tissue expression includes cells sensitive to metabolic abnormalities associated with metabolic syndrome and diabetes mellitus (DM), such as monocytes and macrophages, epithelial cells, adipocytes, hepatocytes, skeletal and cardiac myocytes, pancreatic β-cells, kidney glomeruli and tubules cells, pericytes and pigment epithelium cells of the retina, and Schwann cells. These features make CD36 an important component of the pathogenesis of DM and its complications, but also a promising target in the treatment of these disorders. The detrimental effects of CD36 signaling are mediated by the uptake of fatty acids and modified lipoproteins, deposition of lipids and their lipotoxicity, alterations in insulin response and the utilization of energy substrates, oxidative stress, inflammation, apoptosis, and fibrosis leading to the progressive, often irreversible organ dysfunction. This review summarizes the extensive knowledge of the contribution of CD36 to DM and its complications, including nephropathy, retinopathy, peripheral neuropathy, and cardiomyopathy. Full article
(This article belongs to the Special Issue Scavenger Receptor Structure and Function in Health and Disease)
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Graphical abstract

18 pages, 2129 KiB  
Review
Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure
by Marlene Christina Nielsen, Rasmus Hvidbjerg Gantzel, Joan Clària, Jonel Trebicka, Holger Jon Møller and Henning Grønbæk
Cells 2020, 9(5), 1175; https://doi.org/10.3390/cells9051175 - 9 May 2020
Cited by 122 | Viewed by 14150
Abstract
Macrophages facilitate essential homeostatic functions e.g., endocytosis, phagocytosis, and signaling during inflammation, and express a variety of scavenger receptors including CD163 and CD206, which are upregulated in response to inflammation. In healthy individuals, soluble forms of CD163 and CD206 are constitutively shed from [...] Read more.
Macrophages facilitate essential homeostatic functions e.g., endocytosis, phagocytosis, and signaling during inflammation, and express a variety of scavenger receptors including CD163 and CD206, which are upregulated in response to inflammation. In healthy individuals, soluble forms of CD163 and CD206 are constitutively shed from macrophages, however, during inflammation pathogen- and damage-associated stimuli induce this shedding. Activation of resident liver macrophages viz. Kupffer cells is part of the inflammatory cascade occurring in acute and chronic liver diseases. We here review the existing literature on sCD163 and sCD206 function and shedding, and potential as biomarkers in acute and chronic liver diseases with a particular focus on Acute-on-Chronic Liver Failure (ACLF). In multiple studies sCD163 and sCD206 are elevated in relation to liver disease severity and established as reliable predictors of morbidity and mortality. However, differences in expression- and shedding-stimuli for CD163 and CD206 may explain dissimilarities in prognostic utility in patients with acute decompensation of cirrhosis and ACLF. Full article
(This article belongs to the Special Issue Scavenger Receptor Structure and Function in Health and Disease)
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