Table 1.
Different activation states of neutrophils, circulating monocytes and tissue macrophages in mice.
| Neutrophils | Circulating monocytes | Monocyte-derived macrophages | Resident microglia | ||||
|---|---|---|---|---|---|---|---|
| Subsets | N1/N2 | “Inflammatory” monocytes | “Patrolling” monocytes | M1 | M2 (M2a,b,c) | Surveying microglia | Microglia-derived macrophages |
| Marker genes | iNOS | iNOS | Arg1, CD206, Chil3 (Ym1) | DAP12 | |||
| Receptor expression | CD45high CD11b+ Ly6G+ |
CD45high Ly6Chigh CD115+ CCR2+ CX3CR1int Ly6G- |
CD45high Ly6Clow CD115+ CCR2− CX3CR1+ Ly6G- |
CD45high CD115+ CD11b+ F4/80+ CD68 (ED-1) CCR2+ |
CD45high CD115+ CD11b+ F4/80+ CD68 (ED-1) CX3CR1+ |
CD45int CD11b+ CX3CR1 Ibal+ IB4 |
CD45high CD11b+ CD115+ F4/80+ CD68 (ED-1) CX3CR1+ Iba1+ IB4 |
| Activated by [cells] | Platelets, Endothelial cells | Neutrophils, Dying neurons | Th1, NK | Th2 | Neurons | Dying neurons | |
| Activated by [molecules] | IL-1α | CCL2 | LPS, IFNγ, TNF | IL- 4 and IL-13 (M2a), IL-10, Glucocorticoid, TGFβ (M2c), CCL2 (MCP1) | DAMPs, CX3CL1 | ||
| Function | Neurotoxic (N1), Neuroprotection (N2) | Recruited at sites of inflammation, Precursors of peripheral mononuclear phagocytes | Endothelium integrity | Cytotoxic effect | Phagocytic capacity, Promote neurite outgrowth | Synaptic pruning and remodeling during development, Homeostatic functions | Phagocytosis, Neurotoxicity |
| Cell products | ROS, NO, RNS, MMP-9, NE |
TNF, ROS, NO, IL-1β, Little IL-10 |
IL-10, VEGF |
IL-12, IL-23, TNF, IL-1β, IL-6, ROS |
TGFβ, Arg1 and scavenger receptors (M2a), IL-10 (M2c). |
TGFβ | IL-1β, TNF, IL-6, Chemokines, IFNγ |
The dichotomy in the function of each cell type shown here is an oversimplified view of their activation state. They rather undergo multiple activation phenotypes at a given time making the interpretation of their neuroprotective or/and deleterious effect in cerebral ischemia complex. Whether N1/N2 and M1/M2 phenotypes may apply to neutrophils and microglia, respectively, would need further investigation.
Abbreviations: Arginase 1 (Arg1), Chemokine (C-C motif) ligand 2 (CCL2), C-C chemokine receptor type 2 (CCR2), Chitinase-like 3 (Chil3 or Ym1), CX3C chemokine receptor 1 (CX3CR1), Damage-associated molecular pattern molecules (DAMPs), DNAX activation protein of 12 kDa (DAP12), inducible nitric oxide synthase (iNOS), Interferon gamma (IFNγ), Interleukin-1,4,6,10,12,23 (IL-1, IL-4, IL-6, IL-10, IL-12, IL-23), Ionized calcium binding adaptor molecule 1 (Iba1), Isolectin B4 (IB4), Lipopolysaccharide (LPS), Lymphocyte antigen 6G (Ly6G), Matrix metallopeptidase 9 (MMP-9), monocyte chemotactic protein 1 (MCP1), Natural Killer (NK), Neutrophil elastase (NE), Nitric oxide (NO), Reactive nitrogen species (RNS), Reactive oxygen species (ROS), Transforming growth factor beta (TGF-β), Tumor necrosis factor (TNF), Type 1 T helper (Th1), Type 2 T helper (Th2), Vascular Endothelial Growth Factor (VEGF).