Table 1 Microheterogeneity of selected tissue-resident macrophages: phenotype and functions
Source | Macrophage subpopulation | Functions | Comments |
|---|---|---|---|
Foetal liver | Stromal mϕ | Definitive erythropoiesis | Adhesion receptor distinct from phagocytosis |
| Â | Enucleation of erythrocytes | ||
Foetal monocytes | Â | Â | |
Bone marrow | Monocytes | Monocytosis | Release controlled by CD169 |
Stromal mϕ | Haemopoietic islands, phagocytosis of erythroid nuclei | Sialoadhesin (CD169) and integrin mediate selective adhesion | |
| Â | Haemopoiesis: erythroid (Fe recycling), myeloid (PMN, monocytes, eosinophils); plasma cells | Â | |
Osteoclasts | Bone remodelling | Mutinucleated giant cells CSF1, RANK ligand, vacuolar ATPase, polarised adhesion; F4/80−, CD68+ | |
| Â | Osteoblast interactions | Â | |
Spleen | Red pulp | Clearance of senescent erythrocytes, PMN | F4/80+, CD206+ |
| Â | Haem catabolism, Fe recycling | Induction Spi-C transcription factor | |
Marginal zone, metallophils | Sinusoidal—clearance of polysaccharides, antigens, microbes; stimulate migration | CD169+, CSF-1 dependent | |
Outer marginal zone | Phagocytic | MARCO+, SIGNR-1+, type I interferon induction | |
White pulp | Clearance of apoptotic T and B lymphocytes | F4/80 negative, CD68++ | |
| Â | Migrating metallophils transfer antigen to DC, which migrate to white pulp to activate T and B cells | Â | |
Lymph nodes | Subcapsular macrophages | Analogous to marginal zone | Â |
| Â | Afferent lymph delivers DC and antigens and viruses to lymph node | Subcapsular sinus macrophages capture antigens for delivery to DC, for activation of B and T lymphocytes | |
Medulla | Activation of T and B cells | Filter for mϕ which do not enter efferent lymph | |
Gut | Lamina propria mϕ | Interaction microbiome, epithelium, innate (ILC2/3) and acquired lymphocytes | Active migration beneath epithelium of villi, sample the lumen |
| Â | Modulation of inflammation and immune activation | TGFbeta (F4/80, oral tolerance) | |
Submucosal mϕ | Interactions with smooth muscle cells, myenteric and autonomic nervous system | Peristalsis | |
Peritoneal cavity | Large and small resident mϕ; elicited and activated | Interactions B1 lymphocytes. Inflammation stimulates migration to draining lymph nodes and abdominal organs, such as liver, upon injury | Prototypic in vivo inflammation model Reservoir of mature GATA-6+ macrophages for repair |
Liver | Kupffer cells | Sinusoidal, clearance, phagocytosis and receptor-mediated endocytosis, interactions with hepatocytes, acute phase synthesis through contact and cytokines. Metabolism: iron, lipids, micronutrients. Immune desensitisation | F4/80+, CR3 dim, Kupffer cell-specific CRIG and other lectins. Clearance through CD206, SR-A, also by sinusoidal endothelium |
Lung | Alveolar mϕ | Particle clearance | F4/80 dim, CR3 dim, CD206+ MARCO+, SR-A+ |
| Â | Surfactant metabolism (type 2 alveolar cells) | GM-CSF, PPAR gamma | |
| Â | Immunosuppression by activated alveolar macrophages | Â | |
Bronchial mϕ and DCs | Antigen capture and presentation |  | |
Heart | Resident cardiac macrophages in AV node | Regulate cardiomyocyte electrical activity through macrophage Connexin43- mediated adhesion | Interruption causes heart block |
Resident macrophages in myocardium of foetal origin, bone marrow-derived monocytes and macrophages sourced from other tissues | Response to myocardial ischaemic infarct, repair and tissue remodelling | Heterogeneous origin, including extramedullary haemopoiesis and proliferation, mediated by sympathetic nervous system | |
Large arteries | Tissue resident macrophages supplemented by monocytes | Monocyte adhesion to endothelium, interactions with lipids, smooth muscle cells, foam cell formation | Response to shear force. Atherogenesis and its complications (Table 2) |
Brain | Microglia | Interaction with neurons, live and apoptotic | Resident microglia of yolk sac origin; F4/80+, CR3+ Can be supplemented by bone marrow-derived macrophages |
| Â | Sculpting of synapses via CR3, development and repair; interactions with axons and astrocytes | Microglial activation and complement production contribute to astrocyte activation and neurotoxicity | |
Perivascular mϕ | Clearance lectins and SRs | CD206+, SR-A+ | |
Choroid plexus mϕ | Cerebrospinal fluid secretion |  | |
Meningeal mϕ | Clearance, lymphatic drainage? | Network |