title: A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.
abstract: 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.
authors.affiliation: Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Kurihara
authors.forename: M
authors.initials: M
authors.lastname: Takeya
authors.forename: N
authors.initials: N
authors.lastname: Kamada
authors.forename: M
authors.initials: M
authors.lastname: Kataoka
authors.forename: K
authors.initials: K
authors.lastname: Jishage
authors.forename: O
authors.initials: O
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: T
authors.initials: T
authors.lastname: Higashi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Takashima
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
authors.forename: O
authors.initials: O
authors.lastname: Cynshi
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: H
authors.initials: H
authors.lastname: Kurihara
authors.forename: H
authors.initials: H
authors.lastname: Aburatani
authors.forename: T
authors.initials: T
authors.lastname: Doi
authors.forename: A
authors.initials: A
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Azuma
authors.forename: T
authors.initials: T
authors.lastname: Noda
authors.forename: Y
authors.initials: Y
authors.lastname: Toyoda
authors.forename: H
authors.initials: H
authors.lastname: Itakura
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: T
authors.initials: T
authors.lastname: Kodama
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A