Abandoning M1/M2 for a network model of macrophage function

Abstract

The heart and blood vessels of a healthy individual contain resident immune cells, the majority of which are macrophages that have seeded these organs early in the development. In the mouse, ≈ 10% of noncardiomyocytes are macrophages,1,2 and humans may have comparable numbers.1 After myocardial infarction, macrophage numbers increase in the heart through the combined effects of massive recruitment of bone marrowderived cells and local self-renewal.1,3 Likewise, in atherosclerosis, the chronic lipiddriven inflammatory disease that is the underlying cause of myocardial infarction, macrophage numbers increase in the vessel wall, again because of recruitment and local proliferation.4 Although many of these insights have been generated in mouse models, compelling evidence from genome-wide association studies have associated innate immunity mediators with myocardial infarction,5 whereas prospective human studies have shown that blood monocyte levels can predict cardiovascular events in patients.