Abandoning M1/M2 for a Network Model of Macrophage Function

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, approximate to 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 marrow-derived cells and local self-renewal. 1,3 Likewise, in atherosclerosis, the chronic lipid-driven 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. 6