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. 2015 Jan 14;8:461. doi: 10.3389/fncel.2014.00461

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).