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Encyclopedia of Physical Science and Technology EN008C-380 June 29, 2001 16:42

Lipoprotein/Cholesterol Metabolism 655

TABLE VI Scavenger Receptor Family
Name Ligands Tissue locations
Class A
SR-AI, SR-AII Acetylated LDL, oxidized LDL, polyanions, Macrophages, (Kupffer cells, histiocytes, microglial cells), some
crocidolite asbestos, bacterial endothelial cells (low level)
endotoxin, lipoteichoic acid
MARCO (SR-AIII) Bacteria Macrophages
Class B
SR-BI HDL, LDL, modified lipoproteins, anionic Highest expression in steroidogenic cells (adrenal, ovary, testis) and
phospholipids, acetyl LDL hepatocytes, lower level expression seen in absorptive epithelial
cells of the proximal small intestine, lactating mammary gland, low
levels observed in all cultured cells
CD36 HDL, LDL, modified lipoproteins, anionic Adipose, macrophages, epithelial cells, monocytes, certain endothelial
phospholipids, fatty acids, collagen, malaria- cells, platelets
infected erythrocytes
Croquemort Apoptotic cells Drosophila macrophages
Class C
SR-CI Multiple polyanions, including Drosophila macrophages
modified LDLs, poly(I)
Class D
Microsialin (CD68) Modified lipoproteins Macrophages, Kupffer cells, endothelial cells
Class E
LOX-1 (SR-E1) Oxidized LDL Endothelial cells
Class F
SREC Oxidized LDL Endothelial cells
FcgR2-B2 Oxidized LDL Macrophages

proteins include the cystic fibrosis transmembrane recep- mozygous (or inherit two different mutant alleles). FHA
tor, the sulfonylurea receptor (a pancreatic β-cell protein patients are heterozygous for mutations at the ABCA1
involved in insulin secretion), and the multidrug resis- locus. ABCA1 mutations lower HDL because they pre-
tance transporter proteins. It is thought that ABCA1 me- vent phospholipid and/or cholesterol from effluxing and
diates the efflux of phospholipid and/or cholesterol from becoming associated with apo-A1 and apo-A2. In the ab-
cells, thus making them available for association with sence of sufficient lipid, apo-A1 is rapidly cleared by the
apolipoproteins to form HDL. Its crucial role in this pro- kidneys.
cess was established by the discovery that two types of Why do mutations in ABCA1 lead to premature heart
severe inherited HDL deficiency syndromes are caused disease? ABCA1 fulfills a rate-limiting step in the path-
by mutations in ABCA1 (see Fig. 12). way by which cells get rid of cholesterol, and thus might
be a critical protector against cholesterol overload. With
the exception of hepatocytes, cells are unable to catabolize
XII. TANGIER DISEASE AND FAMILIAL large quantities of cholesterol and must therefore protect
HYPOALPHALIPOPROTEINEMIA themselves from cholesterol overload by expelling choles-
terol to an appropriate extracellular carrier. It is interest-
Tangier disease is a rare recessive disorder in which pa- ing that ABCA1 is especially abundant in macrophages;
tients have almost no HDL. Cholesterol ester accumulates macrophages can become engorged with cholesterol es-
in macrophages and macrophage-rich tissues like spleen ters and form foam cells in the arterial wall. A mutation
and liver. Familial hypoalphalipoproteinemia (FHA) is a in ABCA1 might therefore predispose an individual to
very common dominant disorder in which people have atherosclerosis by impeding cholesterol efflux.
low HDL (typically <30 mg/dl) and suffer from prema- Do HDL levels correlate with the rate of reverse choles-
ture heart disease even without an elevation in LDL. terol transport? Studies of the expression of the SR-B1
Approximately 40% of patients with premature coro- receptor provide an answer to this question. When HDL
nary heart disease have low HDL, making it the most binds to SR-B1 at the plasma membrane of the hepatocyte,
common lipid disorder of heart disease patients. it unloads its cholesterol ester cargo. The lipid-depleted
Tangier disease and FHA are caused by mutations in apo-A1 then is cleared from the circulation, in part by the
the same gene, ABCA1. Tangier disease patients are ho- kidney. High levels of SR-B1 therefore lead to low HDL