Analysis of Macrophage Lineage Cells in Mice Lacking Macrophage Scavenger Receptors

Abstract

Macrophage scavenger receptors (MSR) have been implicated in atherogenesis via receptor mediated uptake of modified lipoproteins and are reportedly cation independent adhesion molecules on macrophages, but their major physiological functions remain obscure. Thus to elucidate their in vivo role, mice lacking both type I and type II MSR were created by gene targeting. Both the heterozygotes and homozygotes in the MSR mutation were normal in appearance and growth, and were fertile. The uptake of oxdized low density lipoprotein (LDL), acetyl LDL and advanced glycosylation end product (AGE) by peritoneal macrophages derived from homozygotes declined to between 25 and 40% as compared with those from the wild type. Numbers of adhesive MSR defected macrophages on a plastic surfaces were <50% compared with those of the wild type. Hepatic granulomas induced by zymosan injection in homozygotes were larger, diffuse and less circumscribed compared with those of the wild type. With regard to phagocytic clearance for apoptotic thymocytes, it has been clarified that MSR accounts for approximetely half of the phagocytic activity required for the uptake of apoptotic thymocytes.
These results indicate that the MRS not only functions to uptake modified LDL but also participates widely in the removal of foreign bodies and waste materials. Moreover, MSR appears to exert multifunctional roles of endocytosis, adhesion and phagocytosis in macrophages.