Scavenger receptor (immunology)

Scavenger receptors are a group of receptors that recognize modified low-density lipoprotein^[1] (LDL) by oxidation or acetylation. This naming is based on a function of cleaning (scavenging): Scavenger receptors widely recognize and take up macromolecules that have a negative charge, like modified LDL.

Function

Scavenger receptors are thought to 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 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 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.^[2]
• Class B has two transmembrane regions.
• Class C is a transmembrane protein whose N-terminus is located extracellularly.

Class A

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.

Members include:

• 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.
• SCARA3
• SCARA4 or COLEC12
• SCARA5
• MARCO : macrophage receptor with collagenous structure

Class B

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.

Members include:

• 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.^[3][4]
• SCARB2
• 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.^[5]

Other

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.^[6]

References

1. Prabhudas M; Bowdish D; Drickamer K; Febbraio M; Herz J; Kobzik L; Krieger M; Loike J; Means TK; Moestrup SK; Post S; Sawamura T; Silverstein S; Wang XY; El Khoury J (2014). "Standardizing scavenger receptor nomenclature". J. Immunol. 192 (5): 1997–2006. doi:10.4049/jimmunol.1490003. PMID 24563502.
2. Matsumoto A; Naito M; Itakura H; Ikemoto S; Asaoka H; Hayakawa I; Kanamori H; Aburatani H; Takaku F; Suzuki H (1990). "Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions". Proc. Natl. Acad. Sci. U.S.A. 87 (23): 9133–7. doi:10.1073/pnas.87.23.9133. PMC 55118. PMID 2251254.
3. Rigotti A; Trigatti BL; Penman M; Rayburn H; Herz J; Krieger M (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". Proc. Natl. Acad. Sci. U.S.A. 94 (23): 12610–5. doi:10.1073/pnas.94.23.12610. PMC 25055. PMID 9356497.
4. Khovidhunkit W (2011). "A genetic variant of the scavenger receptor BI in humans". N. Engl. J. Med. 364 (14): 1375–6; author reply 1376. doi:10.1056/NEJMc1101847#SA1. PMID 21470028.
5. Kuchibhotla S; Vanegas D; Kennedy DJ; Guy E; Nimako G; Morton RE; Febbraio M (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". Cardiovasc. Res. 78 (1): 185–96. doi:10.1093/cvr/cvm093. PMC 2810680. PMID 18065445.
6. Mehta JL; Chen J; Hermonat PL; Romeo F; Novelli G (2006). "Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders". Cardiovasc. Res. 69 (1): 36–45. doi:10.1016/j.cardiores.2005.09.006. PMID 16324688.

External links

• Scavenger receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human scavenger-like receptors in Membranome database