Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Table 1 Secretory substances produced by eosinophils

Substance	Characteristics	Pre-prodiced or de novo synthesysed	Main functions	Ref.
Located within the core of specific (crystalloid) granules
Major basic proteins 1 and 2 (MBP1 and MBP2)	Small highly cationic proteins (MBP2 is less basic)	Pre-produced	Highly cytotoxic to host cells, antihelminthic, antibacterial (MBP1 is more potent and associated with EETosis)	[2,4,32,36]
Located within the matrix of specific (crystalloid) granules
Eosinophil cationic protein (ECP)	Small highly cationic protein with a weak ribonuclease activity (ribonuclease 3)	Pre-produced	Highly cytotoxic to host cells, neurotoxic, antihelminthic, antibacterial, antiviral, associated with EETosis	[2,4,32,36]
Eosinophil-derived neurotoxin	Small basic (less cationic than MBP1 and ECP) protein with a ribonuclease activity (ribonuclease 2)	Pre-produced	Cytotoxic to host cells, neurotoxic, strongly antiviral, antibacterial,	[2,4,32,36]
Eosinophil peroxidase	Highly cationic heme-containing haloperoxidase	Pre-produced	Generates ROS exerting potent antibacterial and antihelminthic effects	[2,4,32,36]
Charcot-Leyden crystal protein (CLC, galectin-10)	Small slightly acidic protein	Probably pre-produced	Unclear, but involvement EETosis and a role in interactions between eosinophils and T-cells are suggested	[31,32,36-38]
Most likely stored within specific granules, but some may be synthesised de novo in the cytoplasm
IL1β, IL2, IL3, IL4, IL5, IL6, IL10, IL11, IL13, IL16, IL18, IL25 (IL17E), IFNγ, GM-CSF, TGFα, TNFα, TNFβ, leukaemia inhibitory factor	Cytokines	Mostly pre-produced; some may be de novo synthesised	A wide range of signaling and regulatory functions	[4,5,32,39]
HB-EGF-LBP, NGF, PDGF, SCF, EGF, VEGF, APRIL	Growth factors	Pre-produced or de novo synthesised	Signalling functions related to cell proliferation and differentiation	[4,5,32]
CCL3, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11 (eotaxin-1), CCL13, CXCL1, CXCL8, CXCL10, CXCL12	Chemokines	Pre-produced or de novo synthesised	Cell migration regulation	[4,5,32,39]
Matrix metalloproteinases MMP9 and MMP17, acid phosphatase, collagenase, arylsulfatase B, histaminase, phospholipase D, catalase, non-specific esterases	Enzymes	Pre-produced or de novo synthesised	Inflammation-related effector functions including cytotoxicity, extracellular matrix modification and phagocytosis	[4,5,32]
Produced within the lipid bodies
Leukotrienes C4, D4 and E4, Thromboxane B2, Prostaglandins E1 and E2, 15-hydroxyeicosatetranoeic acid, platelet-activating factor	Lipid signalling factors, mostly eicosanoids	De novo synthesised	A broad range of effects in inflammatory and allergic responses	[4,5,34]

Table 2 Cell surface markers expressed by eosinophils

Group of surface markers	Markers identified for eosinophils	Ref.
Cytokine and growth factor receptors	IL-2R, IL-3R, IL-4R, IL-5R, IL-9R, IL-10R, IL-13R, IL-17R, IL-23R, IL-27-R, IL-31R, IL-33R (ST2), TSLPR, GM-CSFR, KIT, IFNγR, TGFβR	[5,43-45]
Chemokine and chemoattractant receptors	CCR1, CCR3, CCR4, CCR5, CCR6, CCR8, CCR9, CXCR2, CXCR3, CXCR4, FPR1, FPR2, C3aR, C5aR	[5,43,44,46]
Lipid mediator receptors	Platelet-activating factor receptor, DP1 prostaglandin receptor, DP2 prostaglandin receptor (CRTH2), EP4 prostaglandin receptor, E2 prostaglandin receptor, Leukotriene B4 receptor, Lysophosphatidylserine receptor P2Y10, S1P receptors	[5,43,44,47]
Fc receptors	FcαR, FcγRII, FcγRIII, FcεRI, FcεRII	[5,43,44]
Adhesion molecule receptors	Integrin αLβ2 (LFA1), Integrin αMβ2 (CR3), Integrin αXβ2 (CR4), Integrin α4β1 (VLA4), Integrin α6β1, Integrin αDβ2, Integrin α4β7 (LPAM), cell surface adhesion receptor CD44, CD62L (L-selectin), PSGL1 (P-selectin lipoprotein ligand), CD34, CD244 (2B4)	[5,43,44,48,49]
Pattern recognition receptors	TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR9, TLR10, NOD1, NOD2, RIG-1, RAGE	[5,43,44]
Other receptors and surface markers	PIRB, SIGLECs, SIRPα (shown for mice), LAIR1, Cannabinoid receptor CB2, Kinin B1 and B2 receptors, Histamine receptors, PAR1 or PAR2, CD80 or CD86, CD48, CD300 receptors (a and f), MHC class II	[5,43,44,50-53]