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-A1, SR-A1.1, and MARCO (SR-A6). [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 domain architecture. In 2014 a standard mammalian nomenclature was proposed by a group of 15 immunologists [5] and in 2017 a consensus statement of 25 immunologists reiterated recommendation of this new nomenclature. [2] Acceptance was not universal, however, as later publications have continued to use the legacy names based on roman numerals and human gene symbols. [6] [4]

Nomenclature

The standard nomenclature goes as follows: [2]

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:

Class C

Not found in mammals. Originally found in Drosophila . At least four genes exist. SR-dC1 is relatively well-characterized and is known to bind to acLDL and surface molecules of Gram-positive and Gram-negative bacteria. [11]

Class D

Class E

Class F

Class G

Class H

Class I

Class J

Class K

Class L

Classes to be named

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 3 4 5 6 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.{{cite book}}: CS1 maint: location missing publisher (link)
  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. ↑ Lazzaro, BP (April 2005). "Elevated polymorphism and divergence in the class C scavenger receptors of Drosophila melanogaster and D. simulans". Genetics. 169 (4): 2023–34. doi:10.1534/genetics.104.034249. PMC   1449580 . PMID   15716507.
  12. ↑ 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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