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 athero genesis as a result of receptor-mediated uptake of modified low-densit y Lipoproteins (mLDL)(1-6). MSR-A can bind an extraordinarily wide ran ge of ligands, including bacterial pathogens(7), and also mediates cat ion-independent macrophage adhesion in vitro(8). Here we show that tar geted disruption of the MSR-A gene in mice results in a reduction in t he size of atherosclerotic lesions in an animal deficient in apolipopr otein 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 monocytoge nes or herpes simplex virus type-1, indicating that MSR-A may play a p art in host defence against pathogens.