Scavenger receptor (immunology)

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Scavenger receptor
Identifiers
SymbolScavenger receptor
OPM superfamily 456
OPM protein 5ktf
Membranome 4

Scavenger receptors are a large and diverse superfamily of cell surface receptors. Its properties were first recorded in 1970 by Drs. Brown and Goldstein, with the defining property being the ability to bind and remove modified low density lipoproteins (LDL). [1] Today scavenger receptors are known to be involved in a wide range of processes, such as: homeostasis, apoptosis, inflammatory diseases and pathogen clearance. Scavenger receptors are mainly found on myeloid cells and other cells that bind to numerous ligands, primarily endogenous and modified host-molecules together with pathogen-associated molecular patterns(PAMPs), and remove them. [2] The Kupffer cells in the liver are particularly rich in scavenger receptors, includes SR-A I, SR-A II, and MARCO. [3]

Contents

Function

The scavenger receptor superfamily is defined by its ability to recognize and bind a broad range of common ligands. These ligands include: polyanionic ligands including lipoproteins, apoptotic cells, cholesterol ester, phospholipids, proteoglycans, ferritin, and carbohydrates. [4] This broad recognition range allows scavenger receptors to play an important role in homeostasis and the combating of diseases. This is accomplished via the recognition of various PAMP's and DAMP's, which leads to the removal or scavenging of pathogens with the recognition of PAMP's and the removal of apoptotic cells, self reactive antigens and the products of oxidative stress with the recognition of DAMP's.

In atherosclerotic lesions, macrophages that express scavenger receptors on their plasma membrane take up the oxidized LDL deposited in the blood vessel wall aggressively, and develop into foam cells. Likewise, they secrete various inflammatory cytokines and accelerate the development of atherosclerosis.

Types

Schematic collection of the scavenger receptor superfamily. Classes A-J are displayed with their respective domains. All classes have a mammalian orthologue, with the exception of C. Cells-04-00178-g001.png
Schematic collection of the scavenger receptor superfamily. Classes A-J are displayed with their respective domains. All classes have a mammalian orthologue, with the exception of C.

Scavenger receptors are incredibly diverse and therefore, organized into many different classes, starting at A and continuing to L. [2] This organization is based on their structural properties. Due to the diversity and ongoing research into scavenger receptors, the receptors lack an accepted nomenclature and have been described under different names. In 2014 a new nomenclature [5] was proposed that has been used by some researchers, although no official recognition has been given. [6] [4]

Class A

Class A receptors are a type II membrane protein who use their collagen-like domain for ligand binding.

Members include:Scavenger receptors type 1 (SR-A1), which is a trimer with a molecular weight of about 220-250 kDa (the molecular weight of monomeric protein is about 80 kDa). It preferentially binds modified LDL, either acylated (acLDL) or oxidized (oxLDL). Other ligands include: β-amyloid, heat shock proteins, surface molecules of Gram-positive and Gram-negative bacteria, hepatitis C virus.

SR-A1 can be alternatively spliced to generate a truncation at the C-terminus; it is contained within the Endoplasmatic Reticulum, and just like the unspliced version, has a strong affinity for polyanionic ligand binding.

Class B

CD36 and scavenger receptor class BI are identified as genes encoding for oxidized LDL receptors and classified into scavenger receptor B (SR-B). Both proteins have two transmembrane domains with an extracellular loop, and they are concentrated in a specific plasma membrane microdomain, the caveolae.

Members include:

Other

Some receptors that can bind to oxidized LDL have been discovered.

Related Research Articles

Low-density lipoprotein One of the five major groups of lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein which transport all fat molecules around the body in the extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.

Atherosclerosis Form of arteriosclerosis

Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which arteries are affected.

Lipoprotein

A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.

CD36

CD36, also known as platelet glycoprotein 4, fatty acid translocase (FAT), scavenger receptor class B member 3 (SCARB3), and glycoproteins 88 (GP88), IIIb (GPIIIB), or IV (GPIV) is a protein that in humans is encoded by the CD36 gene. The CD36 antigen is an integral membrane protein found on the surface of many cell types in vertebrate animals. It imports fatty acids inside cells and is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids.

LDL receptor

The low-density lipoprotein (LDL) receptor (LDL-R) is a mosaic protein of 839 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100, which is embedded in the outer phospholipid layer of LDL particles. The receptor also recognizes the apoE protein found in chylomicron remnants and VLDL remnants (IDL). In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19. It belongs to the low density lipoprotein receptor gene family. It is most significantly expressed in bronchial epithelial cells and adrenal gland and cortex tissue.

ICAM-1

ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.

RAGE (receptor)

RAGE, also called AGER, is a 35 kilodalton transmembrane receptor of the immunoglobulin super family which was first characterized in 1992 by Neeper et al. Its name comes from its ability to bind advanced glycation endproducts (AGE), which include chiefly glycoproteins, the glycans of which have been modified non-enzymatically through the Maillard reaction. In view of its inflammatory function in innate immunity and its ability to detect a class of ligands through a common structural motif, RAGE is often referred to as a pattern recognition receptor. RAGE also has at least one other agonistic ligand: high mobility group protein B1 (HMGB1). HMGB1 is an intracellular DNA-binding protein important in chromatin remodeling which can be released by necrotic cells passively, and by active secretion from macrophages, natural killer cells, and dendritic cells.

VLDL receptor

The very-low-density-lipoprotein receptor (VLDLR) is a transmembrane lipoprotein receptor of the low-density-lipoprotein (LDL) receptor family. VLDLR shows considerable homology with the members of this lineage. Discovered in 1992 by T. Yamamoto, VLDLR is widely distributed throughout the tissues of the body, including the heart, skeletal muscle, adipose tissue, and the brain, but is absent from the liver. This receptor has an important role in cholesterol uptake, metabolism of apolipoprotein E-containing triacylglycerol-rich lipoproteins, and neuronal migration in the developing brain. In humans, VLDLR is encoded by the VLDLR gene. Mutations of this gene may lead to a variety of symptoms and diseases, which include type I lissencephaly, cerebellar hypoplasia, and atherosclerosis.

Foam cell Fat-laden M2 macrophages seen in atherosclerosis

Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger heart attacks and stroke.

The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes. It is the first member of a family of endocytic receptors that includes Endo180 (CD280), M-type PLA2R, and DEC-205 (CD205).

Low-density lipoprotein receptor-related protein 8 Cell surface receptor, part of the low-density lipoprotein receptor family

Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the LRP8 gene. ApoER2 is a cell surface receptor that is part of the low-density lipoprotein receptor family. These receptors function in signal transduction and endocytosis of specific ligands. Through interactions with one of its ligands, reelin, ApoER2 plays an important role in embryonic neuronal migration and postnatal long-term potentiation. Another LDL family receptor, VLDLR, also interacts with reelin, and together these two receptors influence brain development and function. Decreased expression of ApoER2 is associated with certain neurological diseases.

OLR1

Oxidized low-density lipoprotein receptor 1 also known as lectin-type oxidized LDL receptor 1 (LOX-1) is a protein that in humans is encoded by the OLR1 gene.

LRP1

Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene. LRP1 is also a key signalling protein and, thus, involved in various biological processes, such as lipoprotein metabolism and cell motility, and diseases, such as neurodegenerative diseases, atherosclerosis, and cancer.

SCARB1

Scavenger receptor class B type 1 (SRB1) also known as SR-BI is a protein that in humans is encoded by the SCARB1 gene. SR-BI functions as a receptor for high-density lipoprotein.

MSR1

Macrophage scavenger receptor 1, also known as MSR1, is a protein which in humans is encoded by the MSR1 gene. MSR1 has also been designated CD204.

STAB1 Protein-coding gene in the species Homo sapiens

Stabilin-1 is a protein that in humans is encoded by the STAB1 gene.

MARCO

Macrophage receptor MARCO also known as macrophage receptor with collagenous structure (MARCO) is a protein that in humans is encoded by the MARCO gene. MARCO is a class A scavenger receptor that is found on particular subsets of macrophages. Scavenger receptors are pattern recognition receptors (PRRs) and are most commonly found on immune cells. Their defining feature is that they bind to polyanions and modified forms of a type of cholesterol called low-density lipoprotein (LDL). MARCO is able to bind and phagocytose these ligands and pathogen-associated molecular patterns (PAMPs), leading to the clearance of pathogens as well as causing downstream effects in the cell that lead to inflammation. As part of the innate immune system, MARCO clears, or scavenges, pathogens and leads to inflammatory responses. The scavenger receptor cysteine-rich (SRCR) domain at the end of the extracellular side of MARCO is responsible for ligand binding and the subsequent immune responses. MARCO expression on macrophages is also associated with diseases since Alzheimer's disease is associated with decreased response within the cell when a ligand binds to MARCO.

TNFRSF18

Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced TNFR-related protein (GITR) or CD357. GITR is encoded and tnfrsf18 gene at chromosome 4 in mice. GITR is type I transmembrane protein and is described in 4 different isoforms. GITR human orthologue, also called activation-inducible TNFR family receptor (AITR), is encoded by the TNFRSF18 gene at chromosome 1.

CD36 antigen is a transmembrane, highly glycosylated, glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissues. CD36 recognises oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin and Plasmodium falciparum infected erythrocytes.

Apoptotic-cell associated molecular patterns (ACAMPs) are molecular markers present on cells which are going through apoptosis, i.e. programmed cell death. The term was used for the first time by C. D. Gregory in 2000. Recognition of these patterns by the pattern recognition receptors (PRRs) of phagocytes then leads to phagocytosis of the apoptotic cell. These patterns include eat-me signals on the apoptotic cells, loss of don’t-eat-me signals on viable cells and come-get-me signals ) secreted by the apoptotic cells in order to attract phagocytes. Thanks to these markers, apoptotic cells, unlike necrotic cells, do not trigger the unwanted immune response.

References

  1. ↑ Patten DA, Shetty S (2018). "More Than Just a Removal Service: Scavenger Receptors in Leukocyte Trafficking". Frontiers in Immunology. 9: 2904. doi: 10.3389/fimmu.2018.02904 . PMC   6315190 . PMID   30631321.
  2. 1 2 PrabhuDas MR, Baldwin CL, Bollyky PL, Bowdish DM, Drickamer K, Febbraio M, et al. (May 2017). "A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease". Journal of Immunology. 198 (10): 3775–3789. doi:10.4049/jimmunol.1700373. PMC   5671342 . PMID   28483986.
  3. ↑ Murphy K, Weaver C (2017). Janeway's immunobiology (Ninth ed.). New York, NY, USA. ISBN   978-0-8153-4505-3. OCLC   933586700.
  4. 1 2 Zani IA, Stephen SL, Mughal NA, Russell D, Homer-Vanniasinkam S, Wheatcroft SB, Ponnambalam S (May 2015). "Scavenger receptor structure and function in health and disease". Cells. 4 (2): 178–201. doi: 10.3390/cells4020178 . PMC   4493455 . PMID   26010753.
  5. ↑ Prabhudas M, Bowdish D, Drickamer K, Febbraio M, Herz J, Kobzik L, et al. (March 2014). "Standardizing scavenger receptor nomenclature". Journal of Immunology. 192 (5): 1997–2006. doi:10.4049/jimmunol.1490003. PMC   4238968 . PMID   24563502.
  6. ↑ Pombinho R, Sousa S, Cabanes D (November 2018). "Scavenger Receptors: Promiscuous Players during Microbial Pathogenesis". Critical Reviews in Microbiology. 44 (6): 685–700. doi:10.1080/1040841X.2018.1493716. PMID   30318962. S2CID   52983025.
  7. ↑ Matsumoto A, Naito M, Itakura H, Ikemoto S, Asaoka H, Hayakawa I, et al. (December 1990). "Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions". Proceedings of the National Academy of Sciences of the United States of America. 87 (23): 9133–7. Bibcode:1990PNAS...87.9133M. doi: 10.1073/pnas.87.23.9133 . PMC   55118 . PMID   2251254.
  8. ↑ Rigotti A, Trigatti BL, Penman M, Rayburn H, Herz J, Krieger M (November 1997). "A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism". Proceedings of the National Academy of Sciences of the United States of America. 94 (23): 12610–5. Bibcode:1997PNAS...9412610R. doi: 10.1073/pnas.94.23.12610 . PMC   25055 . PMID   9356497.
  9. ↑ Khovidhunkit W (April 2011). "A genetic variant of the scavenger receptor BI in humans". The New England Journal of Medicine. 364 (14): 1375–6, author reply 1376. doi:10.1056/nejmc1101847. PMID   21470028.
  10. ↑ Kuchibhotla S, Vanegas D, Kennedy DJ, Guy E, Nimako G, Morton RE, Febbraio M (April 2008). "Absence of CD36 protects against atherosclerosis in ApoE knock-out mice with no additional protection provided by absence of scavenger receptor A I/II". Cardiovascular Research. 78 (1): 185–96. doi:10.1093/cvr/cvm093. PMC   2810680 . PMID   18065445.
  11. ↑ Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G (January 2006). "Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders". Cardiovascular Research. 69 (1): 36–45. doi: 10.1016/j.cardiores.2005.09.006 . PMID   16324688.
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