The macrophage scavenger receptor at 30 years of age: current knowledge and future challenges

It is now thirty years since the original observation that macrophages take up and degrade modified forms of low density lipoprotein (LDL). Molecular cloning has identified multiple scavenger receptors that can endocytose modified LDL and binding studies continue to identify a wide range of scavenger receptor ligands displayed by bacterial pathogens, modified self proteins and apoptotic cells. Scavenger receptors drive macrophage foam cell development in vitro but their exact role in the development of atherosclerosis remains difficult to assess critically. This could be due in part to functional redundancy or it could perhaps reflect our incomplete appreciation of all the potential roles of this family of receptors in host defense and tissue homeostasis. In this brief overview of the extensive literature in this area we emphasize the continuing duality of scavenger receptors as sensors of both nonself (pathogens) and modified self (modified forms of LDL and apoptotic cells). We highlight some under-appreciated roles of scavenger receptors in macrophage biology (e.g., regulation of macrophage cytokine responses) and we speculate on potential approaches to target the activity of this diverse family of receptors for therapeutic benefit in cardiovascular disease.