Roles of Macrophages and Scavenger Receptors in Atherogenesis

Multi-ligand, cell surface receptors for modified lipoproteins are called scavenger receptors. They include three classes；class A (type I and type II scavenger receptors and macrophage receptor with collagenous structure designated as MARCO), class B (CD36 and SR-BI), and class C (dSR-CI, Fcγ RII-B2, and CD68/macrosialin). Among these scavenger receptors, type I and II class A macrophage scavenger receptors (MSR-A) are trimeric glycoproteins which mediate the recognition and uptake of a wide range of negatively charged macromolecules and are implicated in the deposition of cholesterol in arterial walls during atherogenesis through the receptor-mediated endocytosis of chemically modified low density lipoproteins (LDL). In the early lesions of atherosclerosis, it has been confirmed that blood monocytes migrate into the intima, differentiate into macrophages, and transform into foam cells by ingesting modified LDL. In order to analyze the mechanisms of monocyte chemotaxis and transformation of monocytes into foamy macrophages, we made a model system of aortic walls. Ultrastructural observation of transmigration of monocytes into collagen gel through the endothelial cell layer was performed