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). 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. The Kupffer cells in the liver are particularly rich in scavenger receptors, includes SR-A1, SR-A1.1, and MARCO (SR-A6).

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. 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

thumb|524x524px|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. and in 2017 a consensus statement of 25 immunologists reiterated recommendation of this new nomenclature.

  • Class B has two transmembrane regions, one on each end.
  • Class C is a transmembrane protein whose N-terminus is located extracellularly.

Nomenclature

The standard nomenclature goes as follows: Besides LDL and HDL, SR-B1 binds to viruses and bacteria. SR-B1 is located on hepatocytes, steroidogenic cells, arterial wall and macrophages. Mutations in SR-B1 have a negative effect on fertility and innate immune response, and leads to an increase in atherosclerosis.

  • SCARB2: not included in the immunologists' SR-B nomenclature. CD36 can be found in many different cells, for example, insulin-responsive cells, hematopoietic cells like platelets, monocytes, and macrophages, endothelial cells, and specialized epithelial cells in the breast and the eye.

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.

Class D

  • SR-D1: CD68 and its mouse homologue, macrosialin, has a unique N-terminal mucin-like domain. Mucin is a naturally occurring viscous substance that is composed of a protein and covalently linked polysaccharides.

Class E

  • SR-E1: OLR1 / LOX-1. Was isolated from an aortic endothelial cell; recently, it has been discovered in macrophages and vascular smooth muscle cells in artery vessels. The expression of LOX-1 is induced by inflammatory stimuli, so LOX-1 is thought to be involved in the development of atherosclerotic lesions.
  • SR-E2: CLEC7A
  • SR-E3: CD206/MRC1
  • SR-E4: ASGPR

Class F

  • SR-F1: SCARF1
  • SR-F2: MEGF10

Class G

  • SR-G1: CXCL16

Class H

  • SR-H1: STAB1 uptake of slightly oxidized LDL
  • SR-H2: STAB2 uptake of heavily oxidized LDL

Class I

  • SR-I1: CD163
  • SR-I2: CD163L1
  • SR-I3: SCART1

Class J

  • SR-J1: RAGE (gene) membrane form
  • SR-J1.1: soluble form

Class K

  • SR-K1: CD44

Class L

  • SR-L1: LRP1
  • SR-L2: LRP2

Classes to be named

  • SRCRB4D
  • CD14
  • Ly75/CD205
  • CD207/Langerin
  • CD209/DC-SIGN

References

  • Human scavenger-like receptors in Membranome database