Diagrams & Tables: Scavenger Receptors

Scavenger receptors bind a variety of polyanions on bacterial surfaces, stimulating phagocytosis of the polyanion-coated bacteria. Macrophage scavenger receptors appear to mediate important, conserved functions, so may be pattern-recognition receptors that arose early in the evolution of host-defense mechanisms.

Scavenger receptors also bind and internalize modified lipoproteins (LDL), and are expressed on macrophages where they can contribute to foam cell formation in atherosclerosis. Cholesterol-laden macrophage foam cells are the primary component of the fatty streak, which is the earliest atherosclerotic lesion. Thus, lipid uptake by scavenger receptor pathways is considered a requisite and initiating event in the pathogenesis of atherosclerosis. The removal of proinflammatory modified LDLs from the artery wall via scavenger receptors can prove proatherogenic when the metabolic pathways distal to scavenger receptor uptake are overwhelmed, leading to the accumulation of cholesterol-laden macrophages and establishment of a chronic inflammatory setting.

In addition to modified lipoprotein uptake, scavenger receptor proteins regulate apoptotic cell clearance, initiate signal transduction, and serve as pattern recognition receptors for pathogens. These activities may contribute both to proinflammatory and anti-inflammatory forces regulating atherogenesis.[s]

Complement Receptors Fc receptors Immune Cytokines Immunoglobulins Interferons

scavenger receptors	action
Class A - macrophage expressed trimers with cytosol domain, transmembrane domain, spacer domain, α-helical coiled-coil domain, collagen-like domain, +/- cysteine-rich domain. Class A scavenger receptors, macrophages, and atherosclerosis.
human SR-AI/II cysteine-rich domain	expressed by foam cells in athero lesions, binds acetylated and oxLDL
murine SR-AI/II	expressed by foam cells in athero lesions, binds acetylated and oxLDL
MARCO	collagen-like and cysteine-rich domains
SRCL scavenger receptor C-type lectin	endothelial receptor similar in organization to type A scavenger receptors, but contains a C-type carbohydrate-recognition domain (CRD), SRCL might be involved in selective clearance of specific desialylated glycoproteins from circulation and/or interaction of cells bearing Lewis[x]-type structures with the vascular endothelium, shares with the dendritic cell receptor DC-SIGN the ability to bind the Lewis[x] epitope.[s]
Class B - oxidized LDL receptors, concentrated in specific plasma membrane microdomains (caveolae), two transmembrane domains
human CD36	binds oxLDL, expressed by foam cells in athero lesions
murine CD36	binds oxLDL, CD36 knockout mice have less atherosclerosis
murine SR-B1	mediates reverse cholesterol transport (HDL metabolism) (paraoxonase-1, PON-1)
human CLA-1	human homologue of rodent SR-B1
Class C - transmembrane protein with extracellular N-terminus
dSR-C1	Drosophila class C scavenger receptor with a mucin-like structure [s], and with expression restricted to macrophages/hemocytes during embryonic development [s1]
Class D - unique N-terminal mucin-like domain
human CD68	stains all macrophages in athero lesions, binds oxLDL
murine Cd68 (macrosialin)	stains all macrophages in athero lesions, binds oxLDL
Class E - LOX-1 is located in various cell types within atherosclerotic plaque (humans, other animals), and it accumulates during the progression of the plaque. The receptor is highly expressed in hypertension, hyperhomocysteinaemia and diabetes mellitus.
human LOX-1 lectin-like oxidized LDL receptor-1	Binds oxLDL, expressed by endothelial cells, macrophages, smooth muscle cells. Complex interaction exists between LOX-1 and inflammation, lipid accumulation and oxidative stress. The receptor is upregulated by ox-LDL itself and by angiotensin II, endothelin, cytokines, and shear stress.[pm]
not assigned
human SR-PSOX	recently described scavenger receptor cloned from human macrophages