A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.
Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.
Suzuki
H
H
Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan.
Kurihara
Y
Y
Takeya
M
M
Kamada
N
N
Kataoka
M
M
Jishage
K
K
Ueda
O
O
Sakaguchi
H
H
Higashi
T
T
Suzuki
T
T
Takashima
Y
Y
Kawabe
Y
Y
Cynshi
O
O
Wada
Y
Y
Honda
M
M
Kurihara
H
H
Aburatani
H
H
Doi
T
T
Matsumoto
A
A
Azuma
S
S
Noda
T
T
Toyoda
Y
Y
Itakura
H
H
Yazaki
Y
Y
Kodama
T
T
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion; D004198:Disease Susceptibility; D018390:Gene Targeting; D006561:Herpes Simplex / Q000097:blood / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000097:blood; D008088:Listeriosis / Q000097:blood / Q000276:immunology*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D013154:Spleen / Q000382:microbiology / Q000473:pathology
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A