Targets Associated to Immuno Cell Types - Granulocytes

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The Granulocytes category includes the following Cell Ontology parent terms:

granulocytes (CL:0000094) - A leukocyte with abundant granules in the cytoplasm. Synonyms: granular leukocyte, polymorphonuclear leukocyte.

GPCRs
GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
B1 receptor
(Bradykinin receptors)
  • eosinophil (CL:0000771)
  • neutrophil (CL:0000775)
Bradykinin ...
B2 receptor
(Bradykinin receptors)
  • eosinophil (CL:0000771)
  • neutrophil (CL:0000775)
Bradykinin is a vasoactive, pain inducing and pro-inflammatory (phlogistic) kinin released during acute inflammation, and its receptors, B1 and B2, are expressed on eosinophils, and neutrophils. The B2 receptor antagonist icatibant was evaluated in a Phase 2 trial for osteoarthritis [19] ...
CCR3
(Chemokine receptors)
CCR3 is highly expressed on eosinophils, and is the promary receptor mediating their differentiation, chemotaxis and degranulation. It is also expressed on basophils, mast cells, and Th2 lymphocytes.
  • eosinophil (CL:0000771)
  • basophil (CL:0000767)
CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
5-HT2A receptor
(5-Hydroxytryptamine receptors)
Involved in chemotaxis.
  • eosinophil (CL:0000771)
The chemoattractant properties of 5-HT on human eosinophils is mediated by 5-HT2A receptor [10] ...
5-HT7 receptor
(5-Hydroxytryptamine receptors)
  • neutrophil (CL:0000775)
5-HT has been shown to alter cytokine production by dendritic cells via 5-HT4 and 5-HT7 receptors [2] ...
H1 receptor
(Histamine receptors)
Eosinophils express all four histamine receptor subtypes.
  • eosinophil (CL:0000771)
The H1 receptor was the first of the family to be targeted for clinical use, with antagonists (anti-histamines) developed that are still used widely to treat alleric inflammation such as rhinitis, allergic conjunctivitis, urticaria and even anaphylaxis.
H2 receptor
(Histamine receptors)
Eosinophils express all four histamine receptor subtypes.
  • eosinophil (CL:0000771)
Histamine action via the H2 receptor inhibits eosinophil, mast cell and neutrophil chemotaxis, IL-12 production by dendritic cells and also suppresses Th2 cells and cytokine formation. In airway inflammation the H2 receptor mediates bronchial smooth muscle relaxation, vasodilation and mucus production [61] ...
H3 receptor
(Histamine receptors)
Eosinophils express all four histamine receptor subtypes.
  • eosinophil (CL:0000771)
H3 receptor expression is low in peripheral tissues, but high in neuronal mast cells and eosinophils. It is not currently considered an important target in allergy.
H4 receptor
(Histamine receptors)
Eosinophils express all four histamine receptor subtypes.
  • eosinophil (CL:0000771)
H4 receptor is primarily expressed in mast cells and eosinophils, but is also found on human neutrophils and basophils, and plays an important role in modulating eosinophil chemotaxis [56,70] ...
FFA2 receptor
(Free fatty acid receptors)
    FFA2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFA2 (and FFA3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFA2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 ...
    GPR65
    (Class A Orphans)
      Tha expression profile of GPR65 suggests an immunological role. In addition, disruption of GPR65 expression leads to reduced eosinophilia in models of allergic airway disease [44] ...
      S1P3 receptor
      (Lysophospholipid (S1P) receptors)
      Eosinophils express all S1P receptors except S1P2R.
      • eosinophil (CL:0000771)
      In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses.
      S1P1 receptor
      (Lysophospholipid (S1P) receptors)
      Eosinophils express all S1P receptors except S1P2R.
      • eosinophil (CL:0000771)
      S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [30-31,64] ...
      S1P5 receptor
      (Lysophospholipid (S1P) receptors)
      Eosinophils express all S1P receptors except S1P2R.
      • eosinophil (CL:0000771)
      In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses.
      S1P4 receptor
      (Lysophospholipid (S1P) receptors)
      Eosinophils express all S1P receptors except S1P2R.
      • eosinophil (CL:0000771)
      In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses.
      CB2 receptor
      (Cannabinoid receptors)
      Eosinophils do not express CB1 receptor.
      • eosinophil (CL:0000771)
      CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [57] ...
      Enzymes
      GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
      death associated protein kinase 2
      (Death-associated kinase (DAPK) family)
      DAPK2 is the prevailing DAPK family member in granulocytes.
      • granulocyte (CL:0000094)
      DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [26] ...
      FGR proto-oncogene, Src family tyrosine kinase
      (Src family)
      • eosinophil (CL:0000771)
      • neutrophil (CL:0000775)
      Fgr may be involved in neutrophil migration, potentially via binding to intergrins [9] ...
      HCK proto-oncogene, Src family tyrosine kinase
      (Src family)
      • eosinophil (CL:0000771)
      • neutrophil (CL:0000775)
      Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [9] ...
      LYN proto-oncogene, Src family tyrosine kinase
      (Src family)
      • eosinophil (CL:0000771)
      • neutrophil (CL:0000775)
      LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [23-24,66] ...
      cathepsin C
      (C1: Papain)
      • mature neutrophil (CL:0000096)
      • neutrophil (CL:0000775)
      Cathepsin C is a lysosomal cysteine protease constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, catheposin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (g ...
      elastase, neutrophil expressed
      (S1: Chymotrypsin)
      • neutrophil (CL:0000775)
      Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host e ...
      proteinase 3
      (S1: Chymotrypsin)
      • neutrophil (CL:0000775)
      Proteinase 3 (PR3), called myeloblastin when it was first identified, is an abundant serine protease found principally in neutrophil granules (but is also found on the surface of quiescent human neutrophils from peripheral blood). It is stored in the primary granules of circulating neutrophils alongside other cathepsin C-activated neutrophil serine proteases (NSPs), such as human neutrophil elastase (HNE), CatG, and NSP4. In pathological conditions it is thought that PR3 behaves to accelerate inflammation, by enhancing cytokine bioactivity, inactivating anti-inflammatory mediators and by promoting tissue injury (potentially by degrading extra-cellular matrix components like elastin, collagen, fibronectin, and laminins). In addition, imbalances between NSPs and their endogenous inhibitors can contribute towards pathological tissue damage, such as the damage associated with inflammatory lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. PR3 inhibitors are considered to be useful clinical candidates for anti-inflammatory drug development [43] ...
      RAB27A, member RAS oncogene family
      (RAB subfamily)
      RAB27A and its effector JFC1 (synaptotagmin like 1) act to regulate neutrophil exocytosis.
      • neutrophil (CL:0000775)
      Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [37] ...
      Catalytic Receptors
      GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
      TLR6
      (Toll-like receptor family)
      • neutrophil (CL:0000775)
      TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides from bacterial cell membranes, and effect an immune response [22] ...
      Thymic stromal lymphopoietin receptor
      (IL-2 receptor family)
      TLSP receptors have been detected on eosiniphils by mRNA expression and flow cytometry.
      • eosinophil (CL:0000771)
      TLSP/TLSPR signalling promotes release of pro-inflammatory Th2 mediators by mast cells and eosinophils [51] ...
      Other Protein Targets
      GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
      CD33
      (CD molecules)
      • granulocyte (CL:0000094)
      CD33 (SIGLEC-3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [25] ...
      C-type lectin domain family 4 member E
      (C-type lectin-like receptors (CLRs))
      • neutrophil (CL:0000775)
      Mincle is an FcRγ-associated membrane receptor involved in initiating the innate immune response upon recognition of endogenous and exogenous ligands including Sin3A-associated protein (SAP130), α-mannan on fungal cell walls and mycobacterial cord factor (trehalose-6,6′-dimycolate (TDM)) [13] ...
      LILRA4 (CD85g)
      (CD molecules)
      • granulocyte (CL:0000094)
      CD85g is involved in activation of eosinophils and homeostatic regulation of the innate immunity of plasmacytoid dendritic cells (pDCs) [15] ...
      programmed cell death 1 ligand 1 (CD274)
      (CD molecules)
      • granulocyte (CL:0000094)
      PD-L1 is an endogenous ligand of the checkpoint receptor programmed cell death 1 (PD-1). Engagement of PD-1 by PD-L1 has immunosuppressive action. Both the ligand and receptor are being pursued as targets for novel oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Antibody-based therapies targeting the PD-1/PD-L1 pathway augment immune responses and eliminate tumour-induced tolerance. Clinically this action has been observed as regression in various tumour types, including melanoma, renal cell carcinoma [59] ...
      CD300a
      (CD molecules)
      • eosinophil (CL:0000771)
      • neutrophil (CL:0000775)
      CD300a is a member of the CD300 family of leucocyte surface receptors [11] ...
      Fc fragment of IgE receptor Ia
      (Fc epsilon receptors)
      • eosinophil (CL:0000771)
      • basophil (CL:0000767)
      The product of the FCεR1A gene is a single-pass type I membrane protein that is a high-affinity receptor for immunoglobulin E (IgE). It is the ligand binding subunit of the tetrameric FCεRI, exhibiting a Kd of ~0.1nM.
      Fc fragment of IgE receptor II
      (Fc epsilon receptors)
      • eosinophil (CL:0000771)
      FcεRII (CD23) is the low-affinity receptor for immunoglobulin E (IgE) with a Kd > 100nM. This protein is a C-type lectin found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets. It has no structural similarities with other Fc receptors. FcεRII has functions as both a membrane-bound and as a soluble receptor [40,69] ...