A Novel Approach to the Suppression of Atherosclerosis by Fcγ Receptor Blockade

Abstract

See related article, pages 1188–1196 A therosclerosis is associated with immune activation and with systemic immune responses and signs of inflammation.1–3 Atherosclerotic plaques contain a large number of immune cells, particularly macrophages and T cells.4,5 Histopathological and clinical investigations point to immune activation of plaques as a cause of plaque rupture and acute coronary syndromes. Seroepidemiological studies suggest links between atherosclerosis and microbial infections.6,7 Animal studies have identified specific immune cells that play a role in atherogenesis. For example, congenital deficiency of macrophages, lymphocytes, and the Th1 effector pathway, generated by cross-breeding apolipoprotein (apo) E knockout (KO) mice with op/op mutant mice,8 recombinase acting gene-1 KO mice,9 and interferon-γ receptor KO mice,10 respectively, have resulted in the reduction of aherosclerotic lesions. Furthermore, the blockade of c-fms , a receptor for macrophage colony stimulating factor, also caused marked suppression of atherogenesis in apo E-deficient mice, where macrophage differentiation was impaired. These and other studies suggest that …