Monocyte and macrophage heterogeneity in the heart

Abstract

Monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. The cells and their subsets pursue distinct functions in steady-state and disease, and their tenure may range between hours and months. Some subsets are highly inflammatory, whereas others support tissue repair. This review discusses current concepts of lineage relationships and crosstalk of systems, highlights open questions, and describes tools for studying monocyte and macrophage subsets in the murine and human heart.

Keywords: healing; heart failure; macrophages; monocytes; myocardial infarction.

Figure 1

Intravital microscopy of monocyte and neutrophil recruitment in the first 30 minutes after myocardial infarction in GFP reporter mice. Dedicated image stabilization and motion compensation techniques allowed to follow this process in vivo. Interestingly, within the first 30 minutes after injury, the recruitment of monocytes in a transgenic mouse in which green fluorescent protein reports on monocytes (upper row) is faster than recruitment of GFP⁺ cells in a LysM^GFP/+ mouse (lower row and graph on the right. Adapted from reference.

Figure 2

Potential lineage relationships of monocytes and macrophages after myocardial infarction. In steady state, monocyte conversion from Ly-6C^high to Ly-6C^low may occur in blood and bone marrow. It is generally accepted that Ly-6C^high monocytes give rise to inflammatory M1 macrophages in tissue. Other lineage relationships, indicated by dashed arrows, remain to be experimentally explored in the setting of acute MI.

Figure 3

Intravital microscopy of the spleen in a CX3CR1^GFP/+ mouse shortly after myocardial infarction shows intravasation and departure of a splenic monocyte. Adapted from reference.

Figure 4

Open questions about the phenotype, behavior and function of monocytes and macrophages in the remote zone after myocardial infarction. The lower right inset shows immunoreactive staining for CD68⁺ macrophages in the remote zone of a patient who died shortly after MI, reproduced from reference.

Figure 5

Noninvasive imaging of monocytes and macrophages. Left upper panel: hybrid fluorescence molecular tomography / Xray computed tomography imaging of protease activity in an ApoE^-/- mice after coronary ligation (adapted from reference). Right upper panel: PET/MRI in a mouse with acute myocardial infarction using a macrophage-avid, copper-64 labeled cross linked iron oxide nanoparticle (Cu-CLIO, adapted from reference). Lower left panel: T2* weighted magnetic resonance imaging (MRI) after injection of macrophage avid iron oxide nanoparticles (adapted from reference). Lower right panel: imaging of macrophages in a patient with acute MI (adapted from reference).