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Table 1 Microheterogeneity of selected tissue-resident macrophages: phenotype and functions

From: Tissue macrophages: heterogeneity and functions

Source Macrophage subpopulation Functions Comments
Foetal liver Stromal mϕ Definitive erythropoiesis Adhesion receptor distinct from phagocytosis
  Enucleation of erythrocytes
Foetal monocytes   
Bone marrow Monocytes Monocytosis Release controlled by CD169
Stromal mϕ Haemopoietic islands, phagocytosis of erythroid nuclei Sialoadhesin (CD169) and integrin mediate selective adhesion
  Haemopoiesis: erythroid (Fe recycling), myeloid (PMN, monocytes, eosinophils); plasma cells  
Osteoclasts Bone remodelling Mutinucleated giant cells
CSF1, RANK ligand, vacuolar ATPase, polarised adhesion; F4/80, CD68+
  Osteoblast interactions  
Spleen Red pulp Clearance of senescent erythrocytes, PMN F4/80+, CD206+
  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++
  Migrating metallophils transfer antigen to DC, which migrate to white pulp to activate T and B cells  
Lymph nodes Subcapsular macrophages Analogous to marginal zone  
  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
  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+
  Surfactant metabolism (type 2 alveolar cells) GM-CSF, PPAR gamma
  Immunosuppression by activated alveolar macrophages  
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
  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
  1. See text for references
  2. Given the complexity of tissue-resident populations and admixture of recruited monocytes in the steady state and stress, it is important to study properties in situ. These and other organs, not included in this review, also contain interstitial macrophages (not included above)