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.
Pubmed ID: 9069289 RIS Download
Animals | Apolipoproteins E | Arteriosclerosis | Cell Adhesion | Disease Susceptibility | Gene Targeting | Herpes Simplex | Lipoproteins, LDL | Listeriosis | Liver | Macrophages, Peritoneal | Mice | Mice, Inbred C57BL | Mice, Knockout | Receptors, Immunologic | Receptors, Scavenger | Scavenger Receptors, Class A | Spleen