マクロファージのスカベンジャー受容体と動脈硬化

抄録

A hallmark of atherosclerosis is the deposition of plasma cholesterol in atherosclerotic plaques in arterial walls. Key cellular components of atherosclerotic plaques are foam cells, which are derived from monocytes-macrophages. In order to elucidate the molecular mechanism of foam cell formation, we cloned and characterized cDNA for type I and II MSR. Type I and II MSR can bind an extraordinary wide range of ligands using its “charged collagen structure”, including modified low density lipoproteins (mLDL) and bacterial pathogens. MSR also mediates phagocytosis of apoptotic cells and cation-independent macrophage adhesion in vitro. Targeted disruption of type I and II MSR gene in mice results in a marked reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from type I and II MSR deficient mice show a marked decrease in mLDL degradation activity in vitro, whereas mLDL clearance from the plasma occurs at a normal rate. In addition, type I and II MSR-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type I, indicating that type I and II MSR may play a part in host defense against pathogens.