Scavenger receptor (immunology)

Scavenger receptors are a large and diverse

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

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 is mainly expressed in the macrophage, as a protein whose molecular weight is about 80 kDa and makes a trimer; it is composed of 1) cytosol domain, 2) transmembrane domain, 3) spacer domain, 4) alpha-helical coiled-coil domain, 5) collagen-like domain, and 6) cysteine-rich domain.^[7]
• Class B has two transmembrane regions.
• Class C is a transmembrane protein whose
  N-terminus
  is located extracellularly.

Class A

Class A receptors are a

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.

• SCARA1 or MSR1 (SR-A1): besides macrophages they can be found on smooth vascular muscle cells and endothelial tissues; oxidative stress enhances their presence on the endothelium.
• SCARA2 or MARCO (SR-A6): only found on macrophages in the peritoneum, lymph nodes, liver and specific zones of the spleen. Bacteria and lipopolysaccharide produced by bacteria stimulate its expression; SR-A6 is unable to connect with modified LDL.
• SCARA3, MSRL1 or APC7 (SR-A3): plays a significant role in the protection against reactive oxygen species (ROS).
• SCARA4 or
  COLEC12
  (SR-A4): acts as a receptor for the detection, engulfment and destruction of oxidatively modified LDL for vascular endothelial cells.
• SCARA5 or TESR (SR-A5): located in a diverse set of tissues, such as, lung placenta, intestine, heart and epithelial cells, it has a high affinity for bacteria but not for modified LDL.

Class B

• LDL and high-density lipoproteins (HDL), and plays an important role in their transportation into the cells. Recent studies have indicated that SR-B1 is likely to be the major receptor involved in HDL metabolism in mice and humans.^[8][9]
  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
• SCARB3 or
  fatty acids. Furthermore, it has been shown that CD36 is heavily involved with macrophage migration and signalling, together with protecting the host against, bacteria, fungi and malaria parasites. In experimental mice models of atherosclerosis, in which the gene for CD36 has been deleted, the mice have a greatly reduced number of atherosclerotic lesions.^[10]
  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.

• macrosialin, has a unique N-terminal mucin
  -like domain.
• Mucin is a naturally occurring viscous substance (such as found in many nattō or okra) that is composed of a protein and covalently linked polysaccharides. A Drosophila class C scavenger receptor (dSR-C1) also has a mucin-like structure.
• 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.^[11]