title: Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages.
abstract: Modification of low density lipoprotein (LDL) can result in the avid uptake of these lipoproteins via a family of macrophage transmembrane proteins referred to as scavenger receptors (SRs). The genetic inactivation of either of two SR family members, SR-A or CD36, has been shown previously to reduce oxidized LDL uptake in vitro and atherosclerotic lesions in mice. Several other SRs are reported to bind modified LDL, but their contribution to macrophage lipid accumulation is uncertain. We generated mice lacking both SR-A and CD36 to determine their combined impact on macrophage lipid uptake and to assess the contribution of other SRs to this process. We show that SR-A and CD36 account for 75-90% of degradation of LDL modified by acetylation or oxidation. Cholesteryl ester derived from modified lipoproteins fails to accumulate in macrophages taken from the double null mice, as assessed by histochemistry and gas chromatography-mass spectrometry. These results demonstrate that SR-A and CD36 are responsible for the preponderance of modified LDL uptake in macrophages and that other scavenger receptors do not compensate for their absence.
authors.affiliation: Lipid Metabolism Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Vidya V
authors.initials: VV
authors.lastname: Kunjathoor
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Podrez
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Moore
authors.forename: Lorna
authors.initials: L
authors.lastname: Andersson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Koehn
authors.forename: Jeongmi S
authors.initials: JS
authors.lastname: Rhee
authors.forename: Roy
authors.initials: R
authors.lastname: Silverstein
authors.forename: Henry F
authors.initials: HF
authors.lastname: Hoff
authors.forename: Mason W
authors.initials: MW
authors.lastname: Freeman
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism* / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005487:Foam Cells / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005838:Genotype; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D016207:Cytokines; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D003300:Copper; D002784:Cholesterol; D010100:Oxygen