Table 1.
Overview of microglial cell marker proteins, their alternative names, function, and localization.
| Marker | Full name | Synonyms | Functions | References |
|---|---|---|---|---|
| General microglia markers Membrane proteins | ||||
| CD11B | cluster of differentiation 11b | integrin subunit alpha M, ITGAM; complement receptor 3 alpha, CR3A | alpha subunit of an integrin complement receptor part 3 (MAC-1); involved in adhesion processes and uptake of complement-coated molecules | Chakrabarty et al. (2010) and Jeong et al. (2013) |
| CD14 | cluster of differentiation 14 | myeloid cell-specific leucine-rich glycoprotein, monocyte differentiation antigen CD14 | co-receptor for transmembrane TLR4 and endosomal TLR7/9 presenting antigens to them | Baumann et al. (2010) and Zanoni et al. (2011) |
| CD16 | cluster of differentiation 16 | low-affinity immunoglobulin gamma Fc region receptor III, Fc-gamma RIII | Fc receptor detecting immunoglobulin gamma (IgG) antibodies; engaged in phagocytosis processes | Nagarajan et al. (1995) |
| CD40 | cluster of differentiation 40 | tumor necrosis factor receptor superfamily member 5 | transduces signals activating ERK kinase | Lebedeva et al. (2005) |
| CD45 | cluster of differentiation 45 | receptor-type tyrosine-protein phosphatase C, PTPRC | includes enzymatic subunit; positive regulator of T-cell activation | Rice et al. (2017) |
| CD80 | cluster of differentiation 80 | T-lymphocyte activation antigen CD80, Activation B7–1 antigen | together with CD86, CD28, and ICAM1, generates the co-stimulatory signals after MHCII activation | Park et al. (2003) and Lebedeva et al. (2005) |
| CD68 | cluster of differentiation 68 | macrosialin | strongly upregulated during inflammation; it able to internalize from cell surface to endosomes immediately after stimulation | Holness and Simmons (1993), Kurushima et al. (2000) and Fadini et al. (2013) |
| CD115 | cluster of differentiation 115 | macrophage colony-stimulating factor 1 receptor, M-CSFR; colony-stimulating factor 1 receptor, CSF-1R | recognizes pro-inflammatory ligands like IL-34 or CSF-1—cytokines controlling proliferation, differentiation and general functioning of macrophages/microglia | Jenkins et al. (2013) |
| CX3CR1 | CX3C chemokine receptor 1 | fractalkine receptor, C-X3-C CKR-1, Beta chemokine receptor-like 1, CMK-BRL-1, G-protein coupled receptor 13, V28 | microglia migration and adhesion | Jones et al. (2010) |
| TMEM 119 | transmembrane protein 119 | osteoblast induction factor (OBIF) | uncertain | Haynes et al. (2006) and Satoh et al. (2016) |
| F4/80 | cell surface glycoprotein F4/80 | adhesion G protein-coupled receptor E1, EGF-like module-containing mucin-like hormone receptor-like 1, EMR1 | cell surface glycoprotein, expressed in mice, not confirmed in human | Lawson et al. (1990) Lin et al. (2005) and Roesch et al. (2018) |
| FCER1G | high-affinity immunoglobulin epsilon receptor subunit gamma | FcRgamma, Fc-epsilon RI-gamma, FceRI gamma | associates with pattern recognition, C-type lectin-like receptor [pattern recognition receptors (PRRs), C-type lectin-like receptor (CLEC)]; induces downstream signaling leading to maturation of APCs | Baker et al. (2014), Lorenz et al. (2015) and Mukherjee et al. (2019) |
| FCRLS | Fc receptor-like S, scavenger receptor | involved in microglial maintenance | Butovsky and Weiner (2018) | |
| Sirpα | signal regulatory protein alpha | CD172a, SHPS-1, BIT | inhibitory receptor; interacts with a broadly expressed CD47; also called the “do not eat me” signal | Barclay and Van den Berg (2014) and Sierra et al. (2013) |
| Siglec | sialic acid-binding immunoglobulin type lectins | family of proteins, pro-inflammatory immune responses and phagocytosis are turned down in microglia by inhibitory Siglec signaling; less rodent homologs than human | Linnartz-Gerlach et al. (2014) and Smith and Dragunow (2014) | |
| Glut5 | glucose transporter 5 | SLC2A5 | exclusively microglial glucose transporter | Payne et al. (1997) |
| P2Y12 | P2Y purinoceptor 12 | ADPG-R, P2T(AC), P2Y(AC), P2Y(cyc), P2Y12 platelet ADP receptor, short name: P2Y(ADP), SP1999 | detecting nucleotides like ATP released during injuries | Haynes et al. (2006) and Amadio et al. (2014) |
| Intercellular proteins | ||||
| Pu.1 | transcription factor Pu.1 | Spi- 1 | plays a crucial role in determining macrophage lineages and microglial genesis and is a major factor in selecting the set of enhancers expressed by microglia. | Gosselin et al. (2014) and Butovsky and Weiner (2018) |
| IBA-1 | ionized calcium binding adapter molecule 1 | allograft inflammation factor 1 (AIF-1), microglia response factor (MRF-1), daintain | reorganization of microglial cytoskeleton, supporting the phagocytosis process | Sasaki et al. (2001) |
| HexB | β-hexosaminidase subunit β | N-acetyl-beta-glucosaminidase subunit beta | responsible for the degradation of GM2 gangliosides and other molecules containing terminal N-acetyl hexosamines | Butovsky et al. (2014) |
| VIMENTIN | vimentin | fibroblast intermediate filament | key controller for microglia activation | Jiang et al. (2012) |
| Ferritin | ferritin | responsible for iron storage and its homeostasis, which is downregulated in inflammation | Holland et al. (2018) | |
| Sall1 | Sal-like protein 1 | maintenance of microglia homeostasis; its inactivation resulted in the conversion of microglia from resting tissue macrophages into inflammatory phagocytes | Buttgereit et al. (2016) and Butovsky and Weiner (2018) | |
| Activated state markers Membrane proteins | ||||
| CD16 | cluster of differentiation 16 | low-affinity immunoglobulin gamma Fc region receptor III | Fc receptor detecting immunoglobulin gamma (IgG) antibodies; engaged in phagocytosis processes | Nagarajan et al. (1995) and Kigerl et al. (2009) |
| CD32 | cluster of differentiation 32 | low-affinity immunoglobulin gamma Fc region receptor II | membrane receptor for the Fc region of IgG; induces inflammatory signals | Kigerl et al. (2009) |
| CD40 | cluster of differentiation 40 | tumor necrosis factor receptor superfamily member 5 | transduces signals activating ERK kinase | Lebedeva et al. (2005) |
| CD86 | cluster of differentiation 86 | T-lymphocyte activation antigen CD86 or B7–2 | membrane co-stimulatory receptor responsible for immune cell proliferation and IL-2 production | Lebedeva et al. (2005) |
| MHC II | major histocompatibility complex II | mobilizes immune cells to inflammatory response in pathological situation; reacts to TGFβ1 in rodent but not in human | Lebedeva et al. (2005) and Smith and Dragunow (2014) | |
| CD163 | cluster of differentiation 163 | scavenger receptor cysteine-rich type 1 protein M130, hemoglobin scavenger receptor | clears oxidative Hb, which in consequence leads to subsequent degradation of heme by heme oxygenase-1 (HO-1); produces Fe2+, CO and the anti-inflammatory metabolites | Etzerodt and Moestrup (2013) |
| CD206 | cluster of differentiation 206 | macrophage mannose receptor 1 (MRC-1), C-type lectin domain family 13 member D | endocytosis processes via detection of pathogenic glycoproteins and polysaccharide chains | Park et al. (2016) and Ohgidani et al. (2017) |
| Intercellular proteins | ||||
| TSPO | translocator protein | peripheral benzodiazepine receptor (PBR) | immunomodulation, regulation of apoptosis, cell proliferation | Pannell et al. (2020) |
| textitiNOS | inducible nitric oxide synthase | hepatocyte NOS, NOS type II, Peptidyl-cysteine S-nitrosylase NOS2 | enzyme producing NO from L-arginine, promotes response against tumors and pathogens via NO production; promotes synthesis of inflammatory factors (IL-6) and is related with expression of transcription factors, e.g., IRF-1 and NF-κB | Vuolteenaho et al. (2009), Sierra et al. (2014) and Bogdan (2015) |
| ARG1 | arginase 1 | type I arginase, liver-type arginase | enzyme converting an amino acid arginine into ornithine and urea further metabolized to proline and polyamides; needed for wound healing or tissue remodeling, expressed in mice, not confirmed in human | Hesse et al. (2001), Munder (2009), Munder et al. (2005), Quirié et al. (2013), Franco and Fernández-Suárez (2015) |
| Ym1 | chitinase-like protein 3 | beta-N-acetylhexosaminidase Ym1, Chitinase-3-like protein 3, Chi3l3, ECF-L, Eosinophil chemotactic cytokine | heparin-binding lectin; prevents degradation of extracellular matrix components; expressed in mice, not confirmed in human | Pauleau et al. (2004), Odegaard et al. (2007), Odegaard et al. (2008) and Franco and Fernández-Suárez (2015) |
| FIZZ1 | restin-like alpha | cysteine-rich secreted protein FIZZ1, RELMalpha | mediates interactions between sensory nerves and inflammatory cells in lung; blocks nerve growth factor-induced survival of dorsal root ganglion neurons; expressed in mice, not confirmed in human | Pauleau et al. (2004), Odegaard et al. (2007), Odegaard et al. (2008) and Franco and Fernández-Suárez (2015) |
| Extracellular proteins | ||||
| MMP9 | matrix metalloproteinase 9 | gelatinase B | regulates bioavailability of cytokines and chemokines in inflammation; promotes pro-inflammatory IL-1β maturation | Könnecke and Bechmann (2013) and Nissinen and Kähäri (2014) |
| MMP12 | matrix metalloproteinase 12 | macrophage metalloelastase | regulates bioavailability of cytokines and chemokines in inflammation | Nissinen and Kähäri (2014) |
As a reference for the protein name synonyms, www.uniprot.org was used.