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Scavenger receptors are a group of receptors that recognize modified low-density lipoprotein (LDL) by oxidation or acetylation. This naming is based on a function of cleaning (scavenging): Scavenger receptors widely recognize and uptake macromolecules having a negative charge as well as modified LDL.
It is thought that scavenger receptors participate in the removal of many foreign substances and waste materials in the living body by extensive ligand specificity and a variety of receptor molecules.
In atherosclerotic lesions, macrophages that express scavenger receptors on their plasma membrane aggressively uptake the oxidized LDL deposited in the blood vessel wall inside and develop into foam cells, likewise they secrete various inflammatory cytokines and accelerate the development of atherosclerosis.
Scavenger receptors are categorized into classes A, B, and C according to their structural characteristics.
- Class A is mainly expressed in the macrophage, and a protein whose molecular weight is about 80 kDa 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.
- Class B has two transmembrane regions.
- Class C is a transmembrane protein whose N-terminus is located extracellularly.
Scavenger receptors type 1 (SR-A1) and 2 (SR-A2) are trimers with a molecular weight of about 220-250 kDa (the molecular weight of monomeric protein is about 80 kDa). They preferentially bind modified LDL, either acylated (acLDL) or oxidized (oxLDL). They have a collagen-like domain, which is essential for ligand binding.
- SCARA1 or MSR1: SR-A1 scavenger receptors have a cysteine-rich domain, which can be found in a series of cell surface receptors and soluble proteins, but SR-A2 do not.
- SCARA2 or MARCO: Another scavenger receptor class A, MARCO, has collagen-like and cysteine-rich domains.
- SCARA4 or COLEC12
CD36 and scavenger receptor class BI (SR-BI) are identified as oxidized LDL receptors and classified into class B. Both proteins have two transmembrane domains, and they are concentrated in a specific plasma membrane microdomain, the caveolae.
- SCARB1. SR-BI can interact not only with oxidized LDL but also with normal LDL and high-density lipoproteins (HDL). Recent studies have indicated that SR-BI is likely to be the major receptor involved in HDL metabolism in mice and humans.
- SCARB3 or CD36. CD36 has been thought to be implicated in cell adhesion, in the phagocytosis of apoptotic cells, and in the metabolism of long-chain fatty acids. 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.
Some receptors that can bind to oxidized LDL have been discovered.
- CD68 and its mouse homologue, macrosialin, has a unique N-terminal mucin-like domain.
- Mucin is a viscous substance (found in natto or okra) that is composed of a protein and polysaccharides binding it. A Drosophila class C scavenger receptor (dSR-C1) also has a mucin-like structure.
- Lectin-like oxidized LDL receptor-1 (LOX-1) was isolated from an aortic endothelial cell, and recently it has been discovered in macrophages and vascular smooth muscle cells in artery vessels. The expression of LOX-1 is inducted by inflammatory stimuli, so LOX-1 is thought to be involved in the development of atherosclerotic lesions.
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